UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
 
FORM 10-Q
(Mark One)
Quarterly report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
For the quarterly period ended March 31, 20212022
or
Transition report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
For the transition period from              to             
Commission File Number: 001-33500
JAZZ PHARMACEUTICALS PUBLIC LIMITED COMPANY
(Exact name of registrant as specified in its charter) 
Ireland98-1032470
(State or other jurisdiction of
incorporation or organization)
(I.R.S. Employer
Identification No.)
Fifth Floor, Waterloo Exchange,
Waterloo Road, Dublin 4, Ireland D04 E5W7
011-353-1-634-7800
(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)
Securities registered pursuant to Section 12(b) of the Act:
Title of each classTrading Symbol(s)Name of each exchange on which registered
Ordinary shares, nominal value $0.0001 per shareJAZZThe Nasdaq Stock Market LLC

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.    Yes      No  
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).    Yes      No  
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filerAccelerated filer
Non-accelerated filerSmaller reporting company
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.







Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).  Yes  No 
As of April 27, 2021, 56,895,9442022, 62,318,745 ordinary shares of the registrant, nominal value $0.0001 per share, were outstanding.


Table of Contents
JAZZ PHARMACEUTICALS PLC
QUARTERLY REPORT ON FORM 10-Q FOR THE QUARTER ENDED MARCH 31, 20212022

INDEX
 
Page
Item 1.
Item 2.
Item 3.
Item 4.
Item 1.
Item 1A.
Item 2.
Item 6.

We own or have rights to various copyrights, trademarks, and trade names used in our business in the U.S. and/or other countries, including the following: Jazz Pharmaceuticals®, Xyrem® (sodium oxybate) oral solution, Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution, Epidiolex® (cannabidiol) oral solution, Epidyolex® (the trade name in Europe for Epidiolex), Sunosi® (solriamfetol), Defitelio® (defibrotide sodium), Defitelio® (defibrotide), Erwinaze® (asparaginase Erwinia chrysanthemi), Erwinase®, CombiPlex®, Vyxeos® (daunorubicin and cytarabine) liposome for injection, Vyxeos® liposomal 44 mg/100 mg powder for concentrate for solution for infusion, Zepzelca™Zepzelca® (lurbinectedin), Rylaze® (recombinant Erwinia asparaginase) and Xywav™ (calcium, magnesium, potassium, and sodium oxybates)Sativex® (nabiximols) oral solution. This report also includes trademarks, service marks and trade names of other companies. Trademarks, service marks and trade names appearing in this Quarterly Report on Form 10-Q10‑Q are the property of their respective owners.





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Table of Contents
PART I – FINANCIAL INFORMATION
 
Item 1.Financial Statements

JAZZ PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands)
(Unaudited)
March 31,
2021
December 31,
2020
March 31,
2022
December 31,
2021
ASSETSASSETSASSETS
Current assets:Current assets:Current assets:
Cash and cash equivalentsCash and cash equivalents$2,097,533 $1,057,769 Cash and cash equivalents$490,835 $591,448 
Investments335,000 1,075,000 
Accounts receivable, net of allowancesAccounts receivable, net of allowances413,976 396,490 Accounts receivable, net of allowances572,392 563,360 
InventoriesInventories115,475 95,396 Inventories985,454 1,072,721 
Prepaid expensesPrepaid expenses57,185 62,422 Prepaid expenses117,399 131,413 
Other current assetsOther current assets147,727 152,491 Other current assets243,888 252,392 
Assets held for saleAssets held for sale90,888 — 
Total current assetsTotal current assets3,166,896 2,839,568 Total current assets2,500,856 2,611,334 
Property, plant and equipment, netProperty, plant and equipment, net123,863 127,935 Property, plant and equipment, net257,632 256,837 
Operating lease assetsOperating lease assets125,738 129,169 Operating lease assets83,412 86,586 
Intangible assets, netIntangible assets, net2,108,046 2,195,051 Intangible assets, net6,783,057 7,152,328 
GoodwillGoodwill938,398 958,303 Goodwill1,782,444 1,827,609 
Deferred tax assets, netDeferred tax assets, net258,454 254,916 Deferred tax assets, net314,672 311,103 
Deferred financing costsDeferred financing costs4,724 5,238 Deferred financing costs11,336 12,029 
Other non-current assetsOther non-current assets30,351 25,721 Other non-current assets35,508 40,813 
Total assetsTotal assets$6,756,470 $6,535,901 Total assets$11,768,917 $12,298,639 
LIABILITIES AND SHAREHOLDERS’ EQUITYLIABILITIES AND SHAREHOLDERS’ EQUITYLIABILITIES AND SHAREHOLDERS’ EQUITY
Current liabilities:Current liabilities:Current liabilities:
Accounts payableAccounts payable$77,738 $26,945 Accounts payable$73,336 $100,298 
Accrued liabilitiesAccrued liabilities374,035 352,732 Accrued liabilities604,710 666,304 
Current portion of long-term debtCurrent portion of long-term debt248,613 246,322 Current portion of long-term debt31,000 31,000 
Income taxes payableIncome taxes payable49,334 25,200 Income taxes payable26,677 9,608 
Deferred revenueDeferred revenue2,373 2,546 Deferred revenue1,686 2,093 
Total current liabilitiesTotal current liabilities752,093 653,745 Total current liabilities737,409 809,303 
Deferred revenue, non-currentDeferred revenue, non-current1,852 2,315 Deferred revenue, non-current347 463 
Long-term debt, less current portionLong-term debt, less current portion1,853,033 1,848,516 Long-term debt, less current portion5,992,868 6,018,943 
Operating lease liabilities, less current portionOperating lease liabilities, less current portion136,020 140,035 Operating lease liabilities, less current portion83,078 87,200 
Deferred tax liabilities, netDeferred tax liabilities, net109,915 130,397 Deferred tax liabilities, net1,222,084 1,300,541 
Other non-current liabilitiesOther non-current liabilities105,868 101,148 Other non-current liabilities124,644 116,998 
Commitments and contingencies (Note 11)00
Commitments and contingencies (Note 9)Commitments and contingencies (Note 9)00
Shareholders’ equity:Shareholders’ equity:Shareholders’ equity:
Ordinary sharesOrdinary sharesOrdinary shares
Non-voting euro deferred sharesNon-voting euro deferred shares55 55 Non-voting euro deferred shares55 55 
Capital redemption reserveCapital redemption reserve472 472 Capital redemption reserve472 472 
Additional paid-in capitalAdditional paid-in capital2,694,858 2,633,670 Additional paid-in capital3,239,327 3,534,792 
Accumulated other comprehensive lossAccumulated other comprehensive loss(179,428)(134,352)Accumulated other comprehensive loss(590,720)(400,360)
Retained earningsRetained earnings1,281,726 1,159,894 Retained earnings959,347 830,226 
Total shareholders’ equityTotal shareholders’ equity3,797,689 3,659,745 Total shareholders’ equity3,608,487 3,965,191 
Total liabilities and shareholders’ equityTotal liabilities and shareholders’ equity$6,756,470 $6,535,901 Total liabilities and shareholders’ equity$11,768,917 $12,298,639 



The accompanying notes are an integral part of these condensed consolidated financial statements.
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JAZZ PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED STATEMENTS OF INCOME (LOSS)
(In thousands, except per share amounts)
(Unaudited)
 
Three Months Ended
March 31,
Three Months Ended
March 31,
20212020 20222021
Revenues:Revenues:Revenues:
Product sales, netProduct sales, net$603,531 $530,205 Product sales, net$809,837 $603,531 
Royalties and contract revenuesRoyalties and contract revenues4,050 4,521 Royalties and contract revenues3,884 4,050 
Total revenuesTotal revenues607,581 534,726 Total revenues813,721 607,581 
Operating expenses:Operating expenses:Operating expenses:
Cost of product sales (excluding amortization of acquired developed technologies)Cost of product sales (excluding amortization of acquired developed technologies)40,189 28,657 Cost of product sales (excluding amortization of acquired developed technologies)115,284 40,189 
Selling, general and administrativeSelling, general and administrative260,508 208,400 Selling, general and administrative308,813 260,508 
Research and developmentResearch and development76,573 86,107 Research and development129,981 76,573 
Intangible asset amortizationIntangible asset amortization68,192 62,847 Intangible asset amortization172,094 68,192 
Acquired in-process research and development202,250 
Impairment charge136,139 
Total operating expensesTotal operating expenses445,462 724,400 Total operating expenses726,172 445,462 
Income (loss) from operations162,119 (189,674)
Income from operationsIncome from operations87,549 162,119 
Interest expense, netInterest expense, net(27,376)(18,496)Interest expense, net(70,684)(27,376)
Foreign exchange gain (loss)Foreign exchange gain (loss)943 (1,132)Foreign exchange gain (loss)(10,540)943 
Income (loss) before income tax provision (benefit) and equity in gain of investees135,686 (209,302)
Income tax provision (benefit)18,019 (51,287)
Equity in gain of investees(4,165)(182)
Income before income tax expense and equity in loss (gain) of investeesIncome before income tax expense and equity in loss (gain) of investees6,325 135,686 
Income tax expenseIncome tax expense536 18,019 
Equity in loss (gain) of investeesEquity in loss (gain) of investees4,142 (4,165)
Net income (loss)$121,832 $(157,833)
Net incomeNet income$1,647 $121,832 
Net income (loss) per ordinary share:
Net income per ordinary share:Net income per ordinary share:
BasicBasic$2.16 $(2.82)Basic$0.03 $2.16 
DilutedDiluted$2.09 $(2.82)Diluted$0.03 $2.09 
Weighted-average ordinary shares used in per share calculations - basicWeighted-average ordinary shares used in per share calculations - basic56,468 55,956 Weighted-average ordinary shares used in per share calculations - basic61,865 56,468 
Weighted-average ordinary shares used in per share calculations - dilutedWeighted-average ordinary shares used in per share calculations - diluted58,393 55,956 Weighted-average ordinary shares used in per share calculations - diluted62,907 58,393 















The accompanying notes are an integral part of these condensed consolidated financial statements.
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JAZZ PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)
(In thousands)
(Unaudited)
 
 Three Months Ended
March 31,
 20212020
Net income (loss)$121,832 $(157,833)
Other comprehensive loss:
Foreign currency translation adjustments(46,220)(29,990)
Unrealized gain (loss) on hedging activities, net of income tax provision (benefit) of $163 and ($579), respectively1,144 (4,053)
Other comprehensive loss(45,076)(34,043)
Total comprehensive income (loss)$76,756 $(191,876)



 Three Months Ended
March 31,
 20222021
Net income$1,647 $121,832 
Other comprehensive income (loss):
Foreign currency translation adjustments(190,488)(46,220)
Loss on fair value hedging activities reclassified from accumulated other comprehensive income (loss) to foreign exchange gain (loss), net of income tax benefit of $43 and $—, respectively128 — 
Loss on cash flow hedging activities reclassified from accumulated other comprehensive income (loss) to interest expense, net of income tax benefit of $— and $166, respectively— 1,160 
Unrealized loss on cash flow hedging activities, net of income tax benefit of $— and ($3), respectively— (16)
Other comprehensive loss(190,360)(45,076)
Total comprehensive income (loss)$(188,713)$76,756 






















The accompanying notes are an integral part of these condensed consolidated financial statements.
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JAZZ PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED STATEMENTS OF SHAREHOLDERS’ EQUITY
(In thousands)
(Unaudited)
Ordinary SharesNon-voting Euro DeferredCapital
Redemption
Reserve
Additional
Paid-in
Capital
Accumulated
Other
Comprehensive
Loss
Retained
Earnings
Total
Equity
Ordinary SharesNon-voting Euro DeferredCapital
Redemption
Reserve
Additional
Paid-in
Capital
Accumulated
Other
Comprehensive
Loss
Retained
Earnings
Total
Equity
SharesAmountSharesAmountTotal
Equity
SharesAmountSharesAmountCapital
Redemption
Reserve
Additional
Paid-in
Capital
Balance at December 31, 202056,171 $4,000 $55 $472 $2,633,670 $(134,352)$1,159,894 $3,659,745 
Balance at December 31, 2021Balance at December 31, 202161,633 $4,000 $55 $472 $3,534,792 $(400,360)$830,226 $3,965,191 
Cumulative effect adjustment from adoption of ASU 2020-06Cumulative effect adjustment from adoption of ASU 2020-06— — — — — (333,524)— 127,474 (206,050)
Issuance of ordinary shares in conjunction with exercise of share optionsIssuance of ordinary shares in conjunction with exercise of share options408 — — — — 50,407 — — 50,407 Issuance of ordinary shares in conjunction with exercise of share options207 — — — — 21,729 — — 21,729 
Issuance of ordinary shares in conjunction with vesting of restricted stock unitsIssuance of ordinary shares in conjunction with vesting of restricted stock units294 — — — — — — — — Issuance of ordinary shares in conjunction with vesting of restricted stock units404 — — — — — — — — 
Shares withheld for payment of employee's withholding tax liabilityShares withheld for payment of employee's withholding tax liability— — — — — (23,784)— — (23,784)Shares withheld for payment of employee's withholding tax liability— — — — — (33,776)— — (33,776)
Share-based compensationShare-based compensation— — — — — 34,565 — — 34,565 Share-based compensation— — — — — 50,106 — — 50,106 
Other comprehensive lossOther comprehensive loss— — — — — — (45,076)— (45,076)Other comprehensive loss— — — — — — (190,360)— (190,360)
Net incomeNet income— — — — — — — 121,832 121,832 Net income— — — — — — — 1,647 1,647 
Balance at March 31, 202156,873 $4,000 $55 $472 $2,694,858 $(179,428)$1,281,726 $3,797,689 
Balance at March 31, 2022Balance at March 31, 202262,244 $4,000 $55 $472 $3,239,327 $(590,720)$959,347 $3,608,487 

 Ordinary SharesNon-voting Euro DeferredCapital
Redemption
Reserve
Additional
Paid-in
Capital
Accumulated
Other
Comprehensive
Loss
Retained
Earnings
Total
Equity
SharesAmountSharesAmount
Balance at December 31, 201956,140 $4,000 $55 $472 $2,266,026 $(223,393)$1,067,815 $3,110,981 
Issuance of ordinary shares in conjunction with exercise of share options145 — — — — 13,264 — — 13,264 
Issuance of ordinary shares in conjunction with vesting of restricted stock units214 — — — — — — — — 
Shares withheld for payment of employee's withholding tax liability— — — — — (13,547)— — (13,547)
Share-based compensation— — — — — 28,731 — — 28,731 
Shares repurchased(1,131)— — — — — — (139,053)(139,053)
Other comprehensive loss— — — — — — (34,043)— (34,043)
Net loss— — — — — — — (157,833)(157,833)
Balance at March 31, 202055,368 $4,000 $55 $472 $2,294,474 $(257,436)$770,929 $2,808,500 









 Ordinary SharesNon-voting Euro DeferredCapital
Redemption
Reserve
Additional
Paid-in
Capital
Accumulated
Other
Comprehensive
Loss
Retained
Earnings
Total
Equity
SharesAmountSharesAmount
Balance at December 31, 202056,171 $4,000 $55 $472 $2,633,670 $(134,352)$1,159,894 $3,659,745 
Issuance of ordinary shares in conjunction with exercise of share options408 — — — — 50,407 — — 50,407 
Issuance of ordinary shares in conjunction with vesting of restricted stock units294 — — — — — — — — 
Shares withheld for payment of employee's withholding tax liability— — — — — (23,784)— — (23,784)
Share-based compensation— — — — — 34,565 — — 34,565 
Other comprehensive loss— — — — — — (45,076)— (45,076)
Net income— — — — — — — 121,832 121,832 
Balance at March 31, 202156,873 $4,000 $55 $472 $2,694,858 $(179,428)$1,281,726 $3,797,689 








The accompanying notes are an integral part of these condensed consolidated financial statements.
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Table of Contents

JAZZ PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(In thousands)
(Unaudited) 
 Three Months Ended
March 31,
 20212020
Operating activities
Net income (loss)$121,832 $(157,833)
Adjustments to reconcile net income (loss) to net cash provided by operating activities:
Intangible asset amortization68,192 62,847 
Share-based compensation34,485 28,654 
Impairment charge136,139 
Depreciation4,779 4,527 
Acquired in-process research and development202,250 
Deferred tax benefit(19,110)(63,976)
Provision for losses on accounts receivable and inventory1,083 2,620 
Amortization of debt discount and deferred financing costs15,688 12,000 
Other non-cash transactions7,766 1,793 
Changes in assets and liabilities:
Accounts receivable(18,245)37,861 
Inventories(22,014)(10,235)
Prepaid expenses and other current assets(2,897)(17,843)
Other non-current assets157 505 
Operating lease assets3,690 3,195 
Accounts payable51,292 19,604 
Accrued liabilities13,719 (12,198)
Income taxes payable24,625 20,829 
Deferred revenue(637)(1,180)
Other non-current liabilities4,774 7,316 
Operating lease liabilities, less current portion(4,182)(3,906)
Net cash provided by operating activities284,997 272,969 
Investing activities
Proceeds from maturity of investments760,000 345,000 
Purchases of property, plant and equipment(2,168)(4,830)
Acquired in-process research and development(202,250)
Acquisition of intangible assets(13,000)
Acquisition of investments(20,700)(185,000)
Net cash provided by (used in) investing activities737,132 (60,080)
Financing activities
Proceeds from employee equity incentive and purchase plans50,407 13,264 
Payment of employee withholding taxes related to share-based awards(23,784)(13,547)
Repayments of long-term debt(8,347)(8,347)
Share repurchases(139,053)
Net cash provided by (used in) financing activities18,276 (147,683)
Effect of exchange rates on cash and cash equivalents(641)(948)
Net increase in cash and cash equivalents1,039,764 64,258 
Cash and cash equivalents, at beginning of period1,057,769 637,344 
Cash and cash equivalents, at end of period$2,097,533 $701,602 






 Three Months Ended
March 31,
 20222021
Operating activities
Net income$1,647 $121,832 
Adjustments to reconcile net income to net cash provided by operating activities:
Intangible asset amortization172,094 68,192 
Acquisition accounting inventory fair value step-up adjustment63,943 — 
Share-based compensation50,070 34,485 
Deferred tax benefit(45,339)(19,110)
Non-cash interest expense12,168 15,688 
Depreciation7,617 4,779 
Provision for losses on accounts receivable and inventory2,170 1,083 
Other non-cash transactions(14,701)7,766 
Changes in assets and liabilities:
Accounts receivable(9,723)(18,245)
Inventories(24,812)(22,014)
Prepaid expenses and other current assets23,170 (2,897)
Operating lease assets3,095 3,690 
Other non-current assets979 157 
Accounts payable(27,617)51,292 
Accrued liabilities(23,241)13,719 
Income taxes payable16,767 24,625 
Deferred revenue(523)(637)
Operating lease liabilities, less current portion(3,915)(4,182)
Other non-current liabilities5,130 4,774 
Net cash provided by operating activities208,979 284,997 
Investing activities
Proceeds from maturity of investments— 760,000 
Purchases of property, plant and equipment(12,292)(2,168)
Acquisition of intangible assets(25,000)— 
Acquisition of investments— (20,700)
Net cash (used in) provided by investing activities(37,292)737,132 
Financing activities
Proceeds from employee equity incentive and purchase plans21,729 50,407 
Payment of employee withholding taxes related to share-based awards(33,776)(23,784)
Repayments of long-term debt(258,764)(8,347)
Net cash (used in) provided by financing activities(270,811)18,276 
Effect of exchange rates on cash and cash equivalents(1,489)(641)
Net (decrease) increase in cash and cash equivalents(100,613)1,039,764 
Cash and cash equivalents, at beginning of period591,448 1,057,769 
Cash and cash equivalents, at end of period$490,835 $2,097,533 

The accompanying notes are an integral part of these condensed consolidated financial statements.
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JAZZ PHARMACEUTICALS PLC
NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS
(Unaudited)

1. The Company and Summary of Significant Accounting Policies
Jazz Pharmaceuticals plc is a global biopharmaceutical company dedicatedwhose purpose is to developing and commercializing life-changing medicines thatinnovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases - often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in keyneuroscience and oncology. Within these therapeutic areas. Our focus is in neuroscience, including sleep medicine and movement disorders, and in oncology, including hematologic malignancies and solid tumors. We actively exploreareas, we strive to identify new options for patients including novel compounds,by actively exploring small molecules and biologics, and through innovative delivery technologies.technologies and cannabinoid science.
Our lead marketed products are:
Neuroscience
Xyrem® (sodium oxybate)Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution, a product approved by the U.S. Food and Drug Administration, or FDA, and marketed in the U.S. for the treatment of both cataplexy and excessive daytime sleepiness, or EDS, in narcolepsy patients seven years of age and older;
Xywav™ (calcium, magnesium, potassium, and sodium oxybates) oral solution, a product that contains 92% less sodium than Xyrem, approved by FDAJuly 2020 and launched in the U.S. in November 2020 for the treatment of cataplexy or excessive daytime sleepiness, or EDS, in patients with narcolepsy aged seven years of age and older, and also approved by FDA in August 2021 for the treatment of idiopathic hypersomnia, or IH, in adults and launched in the U.S. in November 2021. Xywav contains 92% less sodium than Xyrem®;
Xyrem (sodium oxybate) oral solution, a product approved by FDA and distributed in the U.S. for the treatment of both cataplexy and EDS in patients seven years of age and older with narcolepsy; Jazz also markets Xyrem in Canada for the treatment of cataplexy in patients with narcolepsy. Xyrem is also approved and distributed in the EU, Great Britain and other markets through a licensing agreement;
Epidiolex® (cannabidiol) oral solution, a product approved by FDA and launched in the U.S. in 2018 by GW Pharmaceuticals plc, or GW, and currently indicated for the treatment of seizures associated with Lennox-Gastaut syndrome, or LGS, Dravet syndrome, or DS, or tuberous sclerosis complex, or TSC, in patients one year of age or older; in the EU (where it is marketed as Epidyolex®) and other markets, it is approved for adjunctive treatment of seizures associated with LGS or DS, in conjunction with clobazam (EU and Great Britain only), in patients 2 years of age and older and for adjunctive treatment of seizures associated with TSC in patients 2 years of age and older;
Sunosi®Sunosi® (solriamfetol), a product approved by FDA and marketed in the U.S., Canada, EU and in EuropeGreat Britain to improve wakefulness in adult patients with EDS associated with narcolepsy or obstructive sleep apnea;apnea, or OSA; and
Zepzelca™Sativex® (nabiximols) oral solution, a product approved and marketed in more than 25 markets outside the U.S. as treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis, or MS, who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.
Oncology
Zepzelca® (lurbinectedin), a product approved by FDA in June 2020 and launched in the U.S. in July 2020 for the treatment of adult patients with metastatic small cell lung cancer, or SCLC, with disease progression on or after platinum-based chemotherapy; in Canada, Zepzelca was approved in September 2021 for the treatment of adults with Stage III or metastatic SCLC, who have progressed on or after platinum-containing therapy;
Rylaze® (recombinant Erwinia asparaginase), a product approved by FDA in June 2021 and launched in the U.S. in July 2021 for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia, or ALL, or lymphoblastic lymphoma, or LBL, in adults and pediatric patients who have developed hypersensitivity to E. coli-derived asparaginase;
Vyxeos® (daunorubicin and cytarabine) liposome for injection, a product approved in the U.S., Canada, EU, Great Britain, and recently in Europe (where it is marketedSwitzerland (marketed as Vyxeos® liposomal 44 mg/100 mg powder for concentrate for solution for infusion)in the EU and Great Britain) for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia, or AML,t-AML, or AML with myelodysplasia-related changes;changes (AML-MRC). An expanded indication was granted in the U.S. for the treatment of newly diagnosed t-AML or AML-MRC in pediatric patients aged 1 year and older; and
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Defitelio® (defibrotide sodium), a product approved in the U.S. and Brazil for the treatment of adult and pediatric patients with hepatic veno-occlusive disease, or VOD, also known as sinusoidal obstruction syndrome, with renal or pulmonary dysfunction following hematopoietic stem cell transplantation, or HSCT, and in Europe (where itJapan for the treatment of hepatic sinusoidal obstruction syndrome (hepatic-veno occlusive disease). It is marketed as Defitelio® (defibrotide))currently approved in the EU, Great Britain and other markets for the treatment of severe hepatic VOD, also known as sinusoidal obstructive syndrome, or SOS, in HSCT therapy. It is indicated in adults and children undergoing HSCT therapy; and
Erwinaze® (asparaginase Erwinia chrysanthemi), a treatment approved in the U.S. and in certain markets in Europe (where it is marketed as Erwinase®) forpediatric patients with acute lymphoblastic leukemia, or ALL, who have developed hypersensitivity to E. coli-derived asparaginase.over 1 month of age.
Throughout this report, unless otherwise indicated or the context otherwise requires, all references to “Jazz Pharmaceuticals,” “the registrant,” "the Company", “we,” “us,” and “our” refer to Jazz Pharmaceuticals plc and its consolidated subsidiaries. Throughout this report, all references to “ordinary shares” refer to Jazz Pharmaceuticals plc’s ordinary shares.
Basis of Presentation
These unaudited condensed consolidated financial statements have been prepared following the requirements of the U.S. Securities and Exchange Commission for interim reporting. As permitted under those rules, certain footnotes and other financial information that are normally required by U.S. generally accepted accounting principles, or U.S. GAAP, can be condensed or omitted. The information included in this Quarterly Report on Form 10‑Q should be read in conjunction with our annual consolidated financial statements and accompanying notes included in our Annual Report on Form 10-K10‑K for the year ended December 31, 2020.2021.
In the opinion of management, these condensed consolidated financial statements have been prepared on the same basis as the annual consolidated financial statements and include all adjustments, consisting only of normal recurring adjustments, considered necessary for the fair presentation of our financial position and operating results. The results for the three months ended March 31, 20212022 are not necessarily indicative of the results to be expected for the year ending December 31, 2021,2022, for any other interim period or for any future period.
Our significant accounting policies have not changed substantially from those previously described in our Annual Report on Form 10-K10‑K for the year ended December 31, 2020.
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2021, other than as described below.
These condensed consolidated financial statements include the accounts of Jazz Pharmaceuticals plc and our subsidiaries, and intercompany transactions and balances have been eliminated.
Our operating segment is reported in a manner consistent with the internal reporting provided to the chief operating decision maker, or CODM. Our CODM has been identified as our chief executive officer. We have determined that we operate in 1 business segment, which is the identification, development and commercialization of meaningful pharmaceutical products that address unmet medical needs.
Use of Estimates
The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets, liabilities, revenues and expenses, and related disclosures in the condensed consolidated financial statements and accompanying notes. Management bases its estimates on historical experience and on assumptions believed to be reasonable under the circumstances. Actual results could differ materially from those estimates.
Adoption of New Accounting Standards
In December 2019,August 2020, the Financial Accounting Standards Board, or FASB, issued ASU No. 2019-12, "Income Taxes (Topic 740)2020-06, “Debt—Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging— Contracts in Entity’s Own Equity (Subtopic 815-40): Simplifying the Accounting for Income Taxes"Convertible Instruments and Contracts in an Entity’s Own Equity”, whichor ASU 2020-06. ASU 2020-06 simplifies the accounting for income taxesconvertible instruments by removing certain exceptionseliminating the requirement to separate embedded conversion features from the general principleshost contract when the conversion features are not required to be accounted for as derivatives under Topic 815, Derivatives and Hedging, or that do not result in the existing guidancesubstantial premiums accounted for income taxes and making other minor improvements. Weas paid-in capital. The Company adopted this standardASU 2020-06 on January 1, 20212022, on a modified retrospective basis. This impacted the accounting for our 1.50% exchangeable senior notes due 2024, or the 2024 Notes, and our 2.00% exchangeable senior notes due 2026, or the 2026 Notes, collectively known as the Exchangeable Senior Notes. As a result of the adoption did not haveof ASU 2020-06, the Exchangeable Senior Notes are now accounted for entirely as liabilities measured at amortized cost. ASU 2020-06 also removes certain settlement conditions that are required for contracts to qualify for equity classification and eliminates the treasury stock method to calculate diluted earnings per share for convertible instruments and requires the use of the if-converted method.
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The adoption of ASU 2020-06 resulted in the following adjustments to the condensed consolidated balance sheet (in thousands):
Balance Sheet Item:December 31, 2021Adoption of ASU 2020-06January 1, 2022
Deferred tax assets, net$311,103 $109 $311,212 
Long-term debt, less current portion6,018,943 206,159 6,225,102 
Retained earnings830,226 127,474 957,700 
Additional paid-in capital3,534,792 (333,524)3,201,268 
Interest expense on the Exchangeable Senior Notes will be lower as a material impact on our consolidated financial statements.
Variable Interest Entity
Inresult of adoption of this guidance. During the three months ended March 31, 2021, we invested in a cell2022 the effect of a protected cell company, or the protected cell, as part of our directors’adoption reduced interest expense, net and officers’ liability risk financing strategy. Based on our controlincreased net income by approximately $12 million and the structure of the protected cell, we concluded that Jazz is the primary beneficiary of the protected cellincreased basic and is required to consolidate the protected cell. The insurance premium payable to the protected cell fordiluted EPS by approximately $0.19 per share. For the three months ended March 31, 2021 and2022, the protected cell’s assets and liabilities asExchangeable Senior Notes were determined to be anti-dilutive. The adoption of March 31, 2021 were immaterial.ASU 2020-06 did not impact our cash flows or compliance with debt covenants.
Significant Risks and Uncertainties
With the global impact of the COVID-19 pandemic, weWe have developedimplemented a comprehensive response strategy including establishing cross-functional response teams and implementing business continuity plansdesigned to manage the ongoing impact of the COVID-19 pandemic on our employees, patients and our business. Since the second quarter of 2020, we have been experiencing financial and other impactsThe prolonged nature of the pandemic is negatively impacting our business in a varied manner due to the emergence of the Delta and given the global economic slowdown, the overall disruption of global healthcare systemsOmicron variants and other variants with increased transmissibility, even in some cases in vaccinated people, limited access to health care provider offices and institutions and the other riskswillingness of patients or parents of patients to seek treatment. We believe these dynamics have negatively impacted new patient starts in the U.S. and uncertainties associated with the pandemic, weEurope. We expect that our business, financial condition, results of operations and growth prospects willmay continue to be adversely affectednegatively impacted by the pandemic on a limited basis that may vary depending on the context. However we have begun to observe, and expect to continue to observe, a gradual normalization in future quarters. patient and health care provider practices, as providers and patients have adapted their behaviors and procedures to the evolving circumstances and as COVID-19 vaccines continue to be administered. With respect to our commercialization activities, the evolving effects of the COVID-19 pandemic continuewhile there continues to have abe some negative impact on demand, new patient starts and treatments for our products arising from the pandemic, primarily due to the inherent limitations of telemedicine and a reprioritization of healthcare resources toward COVID-19.COVID-19, we have seen improvements as healthcare systems have adapted to cope with the ongoing situation. The extent of the impact on our ability to generate sales of and revenues from our approved products, execute on new product launches, our clinical development and regulatory efforts, our corporate development objectives and the value of and market for our ordinary shares, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration and severity of the pandemic, governmental “stay-at-home” orders and travel restrictions, quarantines, social distancing and business closure requirements in the U.S., Ireland and other countries, and the effectiveness of vaccination programs and other actions taken globally to contain and treat the disease.time.
Our business has been substantially dependent on Xyrem and while we expect that our business will continue to be substantially dependent on oxybate product sales from both Xyrem and Xywav, there is no guarantee that we can maintain oxybate salesrevenues at or near historicalcurrent levels, or that oxybate salesrevenues will continue to grow. Our ability to maintain or increase oxybate sales isrevenues and realize the anticipated benefits from our investment in Xywav are subject to a number of risks and uncertainties including, without limitation, those related to the launch of Xywav for the treatment of idiopathic hypersomnia in adults and adoption in that indication; competition from the introduction of authorized generic and generic versions of sodium oxybate and/orand new products for treatment of cataplexy and/or EDS in narcolepsy in the U.S. market and from other competitors; the current and potential impacts of the ongoing COVID-19 pandemic, including the current and expected future negative impact on demand for our products and the uncertainty with respect to our ability to meet commercial demand in the future,products; increased pricing pressure from, changes in policies by, or restrictions on reimbursement imposed by, third party payers,payors, including our ability to obtain and maintain adequate coverage and reimbursement for Xywav and Xyrem; increased rebates required to maintain access to our products; challenges to our intellectual property around Xywav and/or Xyrem, including pending antitrust and Xywav,intellectual property litigation; and continued acceptance of Xywav and Xyrem by physicians and patients and acceptance of Xywav by payers, physicians and patients..
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In addition to risks related specifically to XyremXywav and Xywav,Xyrem, we are subject to other challenges and risks related to successfully commercializing a portfolio of oncology products and other neuroscience products, including Sunosi, Defitelio, Erwinaze, Vyxeos and Zepzelca, and other risks specific to our business and our ability to execute on our strategy, as well as risks and uncertainties common to companies in the pharmaceutical industry with development and commercial operations, including, without limitation, risks and uncertainties associated with: ongoing clinical research activity and related outcomes, obtaining regulatory approval of our late-stage product candidates; effectively commercializing our recently approved or acquired products such as Sunosi,Epidiolex, Zepzelca and Xywav;Rylaze; obtaining and maintaining adequate coverage and reimbursement for our products; contracting and rebates to pharmacy benefit managers that reduces our net revenue; increasing scrutiny of pharmaceutical product pricing and resulting changes in healthcare laws and policy; market acceptance; regulatory concerns with controlled substances generally and the potential for abuse; future legislation, action by the U.S. Drug Enforcement Administration, or DEA, or FDA action authorizing the sale, distribution, use, and insurance reimbursement of non-FDA approved cannabinoid products; delays or problems in the supply of
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our products, loss of single source suppliers or failure to comply with manufacturing regulations; delays or problems with third parties that are part of our manufacturing and supply chain; identifying, acquiring or in-licensing additional products or product candidates; pharmaceutical product development and the inherent uncertainty of clinical success; the challenges of protecting and enhancing our intellectual property rights; complying with applicable regulatory requirements; and possible restrictions on our ability and flexibility to pursue certain future opportunities as a result of our substantial outstanding debt obligations. In addition, the pending acquisitionsuccess of the GW Pharmaceuticals plc, or GW, may not be completedAcquisition will depend, in part, on our ability to realize the currently contemplated timeline or terms, or at all,anticipated benefits from successfully combining our and even if consummated,GW's historical businesses and the integration of our business practices and operations with GW's so that we can fully realize the anticipated benefits of the pending acquisitionacquisition. The anticipated benefits to us of the GW Acquisition may not be realized fully within the expected timeframe or at all or may take longer to realize or cost more than expected, which could materially and adversely affect our business, financial condition, results of operations and growth prospects. Moreover, to the extent the COVID-19 pandemic continues to adversely affect our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties discussed above. We discuss many of these risks, uncertainties and other risk factors in greater detail under Part I, Item 1A in our Annual Report on Form 10-K for the year ended December 31, 2020.
Concentrations of Risk
Financial instruments that potentially subject us to concentrations of credit risk consist of cash, cash equivalents, investments and derivative contracts. Our investment policy permits investments in U.S. federal government and federal agency securities, corporate bonds or commercial paper issued by U.S. corporations, money market instruments, certain qualifying money market mutual funds, certain repurchase agreements, and tax-exempt obligations of U.S. states, agencies and municipalities and places restrictions on credit ratings, maturities, and concentration by type and issuer. We are exposed to credit risk in the event of a default by the financial institutions holding our cash, cash equivalents and investments to the extent recorded on the balance sheet.
We manage our foreign currency transaction risk and interest rate risk within specified guidelines through the use of derivatives. All of our derivative instruments are utilized for risk management purposes, and we do not use derivatives for speculative trading purposes. As of March 31, 2021,2022, we had foreign exchange forward contracts with notional amounts totaling $425.1$610.1 million. As of March 31, 2021,2022, the outstanding foreign exchange forward contracts had a net liability fair value of $10.7$4.7 million. As of March 31, 2021, we had interest rate swap contracts with notional amounts totaling $300.0 million. These outstanding interest rate swap contracts had a net liability fair value of $1.5 million as of March 31, 2021. The counterparties to these contracts are large multinational commercial banks, and we believe the risk of nonperformance is not significant.
We are also subject to credit risk from our accounts receivable related to our product sales. We monitor our exposure within accounts receivable and record a reserve against uncollectible accounts receivable as necessary. We extend credit to pharmaceutical wholesale distributors and specialty pharmaceutical distribution companies, primarily in the U.S., and to other international distributors and hospitals. Customer creditworthiness is monitored and collateral is not required. We monitor deteriorating economic conditions in certain European countries which may result in variability of the timing of cash receipts and an increase in the average length of time that it takes to collect accounts receivable outstanding. Historically, we have not experienced significant credit losses on our accounts receivable and as of March 31, 20212022 and December 31, 2020,2021, allowances on receivables were not material. As of March 31, 2021, two2022, three customers accounted for 81%74% of gross accounts receivable, Express Scripts Specialty Distribution Services, Inc. and its affiliates, or ESSDS, which accounted for 67%55% of gross accounts receivable, and McKesson Corporation and affiliates, or McKesson, which accounted for 14%10% of gross accounts receivable, and Cardinal Health, Inc., or Cardinal, which accounted for 9% of gross accounts receivable. As of December 31, 2020, two2021, three customers accounted for 80%74% of gross accounts receivable, ESSDS, which accounted for 68%52% of gross accounts receivable, McKesson, which accounted for 12% of gross accounts receivable, and McKesson,Cardinal, which accounted for 12%10% of gross accounts receivable.
We depend on single source suppliers for most of our products, product candidates and their active pharmaceutical ingredients, or APIs. With respect to Xyrem,our oxybate products, the API is manufactured for us by a single source supplier and the finished product isproducts are manufactured both by us in our facility in Athlone, Ireland and by our U.S.-based Xyrem supplier.
Recent Accounting Pronouncements
In August 2020,October 2021, the FASB issued ASU No. 2020-06, “Debt—Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging— Contracts in Entity’s Own Equity (Subtopic 815-40)2021-08, “Business Combinations (Topic 805): Accounting for Convertible InstrumentsContract Assets and Contract Liabilities from Contracts with Customers”, which requires entities to recognize and measure contract assets and contract liabilities acquired in a business combination in accordance with ASC 2014-09, “Revenue from Contracts with Customers (Topic 606)”. The update will generally result in an Entity’s Own Equity”, which simplifiesentity recognizing contract assets and contract liabilities at amounts consistent with those recorded by the accounting for convertible instruments by
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eliminatingacquiree immediately before the requirement to separate embedded conversion features from the host contract when the conversion features are not required to be accounted for as derivatives under Topic 815, Derivatives and Hedging, or that do not result in substantial premiums accounted for as paid-in capital. By removing the separation model, a convertible debt instrument will be reported as a single liability instrument with no separate accounting for embedded conversion features. Thisacquisition date rather than at fair value. The new standard also removes certain settlement conditions that are required for contracts to qualify for equity classification and eliminates the treasury stock method to calculate diluted earnings per share for convertible instruments and requires the use of the if-converted method. This new standard will beis effective for uson a prospective basis for fiscal years beginning after December 15, 2021, including interim periods within those fiscal years. Early2022, with early adoption permitted. The new guidance is permitted, but no earlier than the fiscal year beginning after December 15, 2020. We may electnot expected to apply the amendments onhave a retrospective or modified retrospective basis. We are currently evaluating the timing, method of adoption and overallmaterial impact of this standard on our consolidatedresults of operations, financial statements.position, or cash flows.

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2. Acquisition Agreement
GW Transaction Agreement
On February 3, 2021, we announced that we have entered into a definitive transaction agreement, or the GW Transaction Agreement, with GW under which a wholly-owned subsidiary of ours, Jazz Pharmaceuticals UK Holdings Limited,or Acquisition Sub, agreed to acquire GW. The GW Transaction Agreement provides, among other things, that subject to the satisfaction or waiver of the conditions set forth in the GW Transaction Agreement, Acquisition Sub will acquire the entire issued share capital of GW pursuant to a scheme of arrangement under Part 26 of the United Kingdom Companies Act 2006, or Scheme of Arrangement, which we refer to as the GW Acquisition.
Under the GW Transaction Agreement, at the effective time of the Scheme of Arrangement, all GW ordinary shares issued and outstanding will be transferred to Acquisition Sub, and the holders of GW ordinary shares will have the right to receive, for each such share, (a) $16.6623 in cash and (b) an amount of our ordinary shares determined based on the exchange ratio, which exchange ratio will be determined as follows:
If the volume-weighted weighted average sales price of our ordinary shares, as determined in accordance with the GW Transaction Agreement, or the Defined VWAP, is greater than $139.72 but less than $170.76, the exchange ratio will be an amount equal to the quotient obtained by dividing (x) $1.6623 by (y) the Defined VWAP;
If the Defined VWAP is equal to or less than $139.72, the exchange ratio will be 0.011929; or
If the Defined VWAP is an amount equal to or greater than $170.76, the exchange ratio will be 0.009760.
Because each American Depositary Share in GW, or GW ADSs, represents a beneficial interest in 12 GW ordinary shares, holders of GW ADSs will be entitled to receive 12 times the foregoing cash and share amounts, or (1) $200.00 in cash and (2) $20.00 in the form of our ordinary shares with the actual number of our ordinary shares being determined based on the exchange ratio set out above. The total consideration to be paid by us for the entire issued share capital of GW is approximately $7.2 billion.
The GW Transaction Agreement contains customary representations and warranties given by GW and us, covenants regarding the conduct of GW’s business prior to the consummation of the GW Acquisition, termination rights and other customary provisions. The GW Acquisition is expected to close in the first half of May 2021, subject to the satisfaction or waiver of the conditions set forth in the GW Transaction Agreement.

3. Cash and Available-for-Sale Securities
Cash and cash equivalents and investments consisted of the following (in thousands): 
March 31, 2021March 31, 2022
Amortized
Cost
Gross
Unrealized
Gains
Gross
Unrealized
Losses
Estimated
Fair Value
Cash and
Cash
Equivalents
InvestmentsAmortized
Cost
Gross
Unrealized
Gains
Gross
Unrealized
Losses
Estimated
Fair Value
Cash and
Cash
Equivalents
CashCash$851,856 $$$851,856 $851,856 $Cash$410,125 $— $— $410,125 $410,125 
Time deposits1,295,000 1,295,000 960,000 335,000 
Money market fundsMoney market funds285,677 285,677 285,677 Money market funds80,710 — — 80,710 80,710 
TotalsTotals$2,432,533 $$$2,432,533 $2,097,533 $335,000 Totals$490,835 $— $— $490,835 $490,835 
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December 31, 2020December 31, 2021
Amortized
Cost
Gross
Unrealized
Gains
Gross
Unrealized
Losses
Estimated
Fair Value
Cash and
Cash
Equivalents
InvestmentsAmortized
Cost
Gross
Unrealized
Gains
Gross
Unrealized
Losses
Estimated
Fair Value
Cash and
Cash
Equivalents
CashCash$517,117 $$$517,117 $517,117 $Cash$510,747 $— $— $510,747 $510,747 
Time deposits1,360,000 1,360,000 285,000 1,075,000 
Money market fundsMoney market funds255,652 255,652 255,652 Money market funds80,701 — — 80,701 80,701 
TotalsTotals$2,132,769 $$$2,132,769 $1,057,769 $1,075,000 Totals$591,448 $— $— $591,448 $591,448 
Cash equivalents and investments are considered available-for-sale securities. We use the specific-identification method for calculating realized gains and losses on securities sold and include them in interest expense, net in the condensed consolidated statements of income (loss). Our investment balances represent time deposits with original maturities of greater than three months and less than one year.income. Interest income from available-for-sale securities was $1.2$0.2 million and $4.4$1.2 million in the three months ended March 31, 20212022 and 2020,2021, respectively.

4.3. Fair Value Measurement
The following table summarizes, by major security type, our available-for-sale securities and derivative contracts as of March 31, 20212022 and December 31, 20202021 that were measured at fair value on a recurring basis and were categorized using the fair value hierarchy (in thousands): 
March 31, 2021December 31, 2020March 31, 2022December 31, 2021
Quoted
Prices in
Active
Markets for
Identical
Assets
(Level 1)
Significant
Other
Observable
Inputs
(Level 2)
Total
Estimated
Fair Value
Quoted
Prices in
Active
Markets for
Identical
Assets
(Level 1)
Significant
Other
Observable
Inputs
(Level 2)
Total
Estimated
Fair Value  
Quoted
Prices in
Active
Markets for
Identical
Assets
(Level 1)
Significant
Other
Observable
Inputs
(Level 2)
Total
Estimated
Fair Value
Quoted
Prices in
Active
Markets for
Identical
Assets
(Level 1)
Significant
Other
Observable
Inputs
(Level 2)
Total
Estimated
Fair Value  
Assets:Assets:Assets:
Available-for-sale securities:Available-for-sale securities:Available-for-sale securities:
Time deposits$$1,295,000 $1,295,000 $$1,360,000 $1,360,000 
Money market fundsMoney market funds285,677 285,677 255,652 255,652 Money market funds$80,710 $— $80,710 $80,701 $— $80,701 
Foreign exchange forward contractsForeign exchange forward contracts488 488 11,907 11,907 Foreign exchange forward contracts— 3,712 3,712 — 580 580 
TotalsTotals$285,677 $1,295,488 $1,581,165 $255,652 $1,371,907 $1,627,559 Totals$80,710 $3,712 $84,422 $80,701 $580 $81,281 
Liabilities:Liabilities:Liabilities:
Interest rate contracts$$1,527 $1,527 $$2,835 $2,835 
Cross-currency interest rate contractsCross-currency interest rate contracts$— $— $— $— $15,232 $15,232 
Foreign exchange forward contractsForeign exchange forward contracts11,149 11,149 790 790 Foreign exchange forward contracts— 8,418 8,418 — 3,187 3,187 
TotalsTotals$$12,676 $12,676 $$3,625 $3,625 Totals$— $8,418 $8,418 $— $18,419 $18,419 
As of March 31, 2021,2022, our available-for-sale securities included time deposits and money market funds and their carrying values were approximately equal to their fair values. Time deposits were measured at fair value using Level 2 inputs and moneyMoney market funds were measured using quoted prices in active markets, which represent Level 1 inputs. Level 2 inputs, obtained from various third party data providers, represent quoted prices for similar assets in active markets, or these inputs were derived from observable market data, or if not directly observable, were derived from or corroborated by other observable market data.
Our derivative assets and liabilities include interest rate and foreign exchange derivatives that are measured at fair value using observable market inputs such as forward rates interest rates, our own credit risk as well as an evaluation of our counterparties’ credit risks. Basedand based on these inputs, the derivative assets and liabilities are classified within Level 2 of the fair value hierarchy. The cross-currency interest rate swap contract matured on March 31, 2022.
There were no transfers between the different levels of the fair value hierarchy in 20212022 or 2020.2021.
As of March 31, 2022 and December 31, 2021, the carrying amount of investments measured using the measurement alternative for equity investments without a readily determinable fair value was $4.5$5.0 million. The carrying amount, which is recorded within other non-current assets, representsis based on the purchase price paid in 2018.latest observable transaction price.
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As of March 31, 2021,2022, the estimated fair values of our 1.875% exchangeable senior notes due 2021, or the 2021 Notes, our 1.50% exchangeable senior notes due 2024, or the 2024 Notes, and our 2.00% exchangeable senior notes due 2026, or the 2026 Notes, the 4.375% senior secured notes, due 2029, or the Secured Notes, and the seven-year $3.1 billion term loan B facility, or the Dollar Term Loan, were approximately $224$594 million, $625 million$1.2 billion, $1.5 billion and $1.3$3.1 billion respectively. The fair values of the 2021 Notes, the 2024 Notes and the 2026 Notes, which we refer to collectively as the Exchangeable Senior Notes, wereeach of these debt facilities was estimated using quoted market prices obtained from brokers (Level 2).
As of March 31, 2022, assets measured at fair value on a non-recurring basis subsequent to initial recognition included assets classified as held for sale on the condensed consolidated balance sheet. These assets related to an asset purchase agreement with Axsome Therapeutics, or Axsome, pursuant to which Axsome will purchase certain assets related to Sunosi. Refer to Note 15, Assets Held for Sale, for additional information. The carrying amount of $90.9 million for assets held for sale is equal to estimated fair value, of our borrowing under our term loan was approximately equal to its book valuewhich is based on the borrowing rates currently available for variable rate loans (Level 2).sales price agreed less costs to sell, and represents a Level 3 input.

5.4. Derivative Instruments and Hedging Activities
We are exposed to certain risks arising from operating internationally, including fluctuations in interest rates on our outstanding term loan borrowings and fluctuations in foreign exchange rates primarily related to the translation of sterling and euro-denominated net monetary liabilities, including intercompany balances, held by subsidiaries with a U.S. dollar functional currency. We manage these exposures within specified guidelines through the use of derivatives. All of our derivative instruments are utilized for risk management purposes, and we do not use derivatives for speculative trading purposes.
To achieve a desired mix of floating and fixed interest rates onIn order to hedge our variable rate debt,exposure to foreign currency exchange risk associated with our Euro Term Loan, we entered into a cross-currency interest rate swap agreementscontract in March 2017May 2021, which are effective until July 2021. These agreements hedge contractual term loan interest rates. As ofmatured on March 31, 20212022. The terms of this contract converted the principal repayments and December 31, 2020,interest payments on the interest rate swap agreements had a notionalEuro Term Loan into U.S. dollars. The carrying amount of $300.0 million. As a result of these agreements, the interest rate on a portion of our term loan borrowings was fixed at 1.895%, plus the borrowing spread, until July 12, 2021.
The effective portion of changes inEuro Term Loan and the fair value of derivatives designated as, and that qualify as, cash flow hedges is recorded in accumulated other comprehensive loss and is subsequently reclassified into earningsthe cross-currency interest rate swap contract were remeasured on a monthly basis, with changes in the period thateuro to U.S. dollar foreign exchange rates recognized within foreign exchange gain (loss) in the hedged forecasted transaction affects earnings. condensed consolidated statements of income.
The impact on accumulated other comprehensive income (loss) and earnings from derivative instruments that qualified as cash flow hedges for the three months ended March 31, 2021 and 2020cross-currency interest rate swap contract was as follows (in thousands):
Three Months Ended
March 31,
Interest Rate Contracts:20212020
Loss recognized in accumulated other comprehensive loss, net of tax$(16)$(4,200)
Loss reclassified from accumulated other comprehensive loss to interest expense, net of tax1,160 147 
Assuming no change in London Inter-Bank Offered Rate, or LIBOR, based interest rates from market rates as of March 31, 2021, $1.3 million of losses, net of tax, recognized in accumulated other comprehensive loss will be reclassified to earnings over the next 12 months.
Cross-Currency Interest Rate Contract:Three Months Ended
March 31, 2022
Loss reclassified from accumulated other comprehensive income (loss) to foreign exchange gain (loss), net of tax$128 
Loss recognized in foreign exchange gain (loss)(2,646)
We also enter into foreign exchange forward contracts, with durations of up to 12 months, designed to limit the exposure to fluctuations in foreign exchange rates related to the translation of certain non-U.S. dollar denominated liabilities, including intercompany balances. Hedge accounting is not applied to these derivative instruments as gains and losses on these hedge transactions are designed to offset gains and losses on underlying balance sheet exposures. As of March 31, 20212022 and December 31, 2020,2021, the notional amount of foreign exchange contracts where hedge accounting is not applied was $425.1$610.1 million and $357.4$347.2 million, respectively.
The foreign exchange gain (loss) in our condensed consolidated statements of income (loss) included the following losses associated with foreign exchange contracts not designated as hedging instruments (in thousands):
Three Months Ended
March 31,
Three Months Ended
March 31,
Foreign Exchange Forward Contracts:Foreign Exchange Forward Contracts:20212020Foreign Exchange Forward Contracts:20222021
Loss recognized in foreign exchange gain (loss)Loss recognized in foreign exchange gain (loss)$(13,050)$(6,139)Loss recognized in foreign exchange gain (loss)$(21,025)$(13,050)
The cash flow effects of our derivative contracts for the three months ended March 31, 20212022 and 20202021 are included within net cash provided by operating activities in the condensed consolidated statements of cash flows.flows, except for the settlement of notional amounts of the cross-currency interest rate contract, which are included in net cash provided by (used in) financing activities.
To achieve a desired mix of floating and fixed interest rates on our variable rate debt, we entered into interest rate swap agreements in March 2017. In May 2021, we repaid the term loan to which these interest rate swap agreements related, at which point the interest rate swap contracts were de-designated as cash flow hedges. The interest rate swap agreements matured in July 2021.
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The impact on accumulated other comprehensive income (loss) and earnings from interest rate swap contracts for the three months ended March 31, 2021 was as follows (in thousands):
Interest Rate Contracts:Three Months Ended
March 31, 2021
Loss recognized in accumulated other comprehensive income (loss), net of tax$(16)
Loss reclassified from accumulated other comprehensive income (loss) to interest expense, net of tax1,160 
The following tables summarize the fair value of outstanding derivatives (in thousands):
March 31, 2021
Asset DerivativesLiability Derivatives
Balance Sheet LocationFair ValueBalance Sheet LocationFair Value
Derivatives designated as hedging instruments:
Interest rate contractsOther current assets$Accrued liabilities$1,527 
Derivatives not designated as hedging instruments:
Foreign exchange forward contractsOther current assets488 Accrued liabilities11,149 
Total fair value of derivative instruments$488 $12,676 
December 31, 2020ClassificationMarch 31,
2022
December 31,
2021
Asset DerivativesLiability Derivatives
Balance Sheet LocationFair ValueBalance Sheet LocationFair Value
Derivatives designated as hedging instruments:
Interest rate contractsOther current assets$Accrued liabilities$2,835 
AssetsAssets
Derivatives not designated as hedging instruments:Derivatives not designated as hedging instruments:Derivatives not designated as hedging instruments:
Foreign exchange forward contractsForeign exchange forward contractsOther current assets11,907 Accrued liabilities790 Foreign exchange forward contractsOther current assets$3,712 $580 
Total fair value of derivative instruments$11,907 $3,625 
LiabilitiesLiabilities
Derivatives not designated as hedging instruments:Derivatives not designated as hedging instruments:
Foreign exchange forward contractsForeign exchange forward contractsAccrued liabilities$8,418 $3,187 
Derivatives designated as hedging instruments:Derivatives designated as hedging instruments:
Cross-currency interest rate contractCross-currency interest rate contractAccrued liabilities— 15,232 
Total fair value of derivative liability instrumentsTotal fair value of derivative liability instruments$8,418 $18,419 
Although we do not offset derivative assets and liabilities within our condensed consolidated balance sheets, our International Swap and Derivatives Association agreements provide for net settlement of transactions that are due to or from the same counterparty upon early termination of the agreement due to an event of default or other termination event. The following tables summarize the potential effect on our condensed consolidated balance sheets of offsetting our cross-currency interest rate contracts and foreign exchange forward contracts subject to such provisions (in thousands):
March 31, 2021March 31, 2022
Gross Amounts of Recognized Assets/ LiabilitiesGross Amounts Offset in the Consolidated Balance SheetNet Amounts of Assets/ Liabilities Presented in the Consolidated Balance SheetGross Amounts Not Offset in the Consolidated Balance SheetGross Amounts of Recognized Assets/ LiabilitiesGross Amounts Offset in the Consolidated Balance SheetNet Amounts of Assets/ Liabilities Presented in the Consolidated Balance SheetGross Amounts Not Offset in the Consolidated Balance Sheet
DescriptionDescriptionDerivative Financial InstrumentsCash Collateral Received (Pledged)Net AmountDescriptionDerivative Financial InstrumentsCash Collateral Received (Pledged)Net Amount
Derivative assetsDerivative assets$488 $$488 $(488)$$Derivative assets$3,712 $— $3,712 $(3,100)$— $612 
Derivative liabilitiesDerivative liabilities(12,676)(12,676)488 (12,188)Derivative liabilities(8,418)— (8,418)3,100 — (5,318)
December 31, 2020December 31, 2021
Gross Amounts of Recognized Assets/ LiabilitiesGross Amounts Offset in the Consolidated Balance SheetNet Amounts of Assets/ Liabilities Presented in the Consolidated Balance SheetGross Amounts Not Offset in the Consolidated Balance SheetGross Amounts of Recognized Assets/ LiabilitiesGross Amounts Offset in the Consolidated Balance SheetNet Amounts of Assets/ Liabilities Presented in the Consolidated Balance SheetGross Amounts Not Offset in the Consolidated Balance Sheet
DescriptionDescriptionDerivative Financial InstrumentsCash Collateral Received (Pledged)Net AmountDescriptionDerivative Financial InstrumentsCash Collateral Received (Pledged)Net Amount
Derivative assetsDerivative assets$11,907 $$11,907 $(2,207)$$9,700 Derivative assets$580 $— $580 $(567)$— $13 
Derivative liabilitiesDerivative liabilities(3,625)(3,625)2,207 (1,418)Derivative liabilities(18,419)— (18,419)567 — (17,852)

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6.5. Inventories
Inventories consisted of the following (in thousands): 
March 31,
2021
December 31,
2020
March 31,
2022
December 31,
2021
Raw materialsRaw materials$23,415 $16,003 Raw materials$26,335 $21,550 
Work in processWork in process52,117 45,758 Work in process775,804 886,849 
Finished goodsFinished goods39,943 33,635 Finished goods183,315 164,322 
Total inventoriesTotal inventories$115,475 $95,396 Total inventories$985,454 $1,072,721 
As of March 31, 2022 and December 31, 2021 inventories included $727.4 million and $811.3 million, respectively, related to the purchase accounting inventory fair value step-up on inventory acquired in the GW Acquisition.

7.6. Goodwill and Intangible Assets
The gross carrying amount of goodwill was as follows (in thousands):
Balance at December 31, 20202021$958,3031,827,609 
Goodwill allocated to assets held for sale (1)
(12,927)
Foreign exchange(19,905)(32,238)
Balance at March 31, 20212022$938,3981,782,444 
________________________
(1) In March 2022, we entered into a definitive agreement to divest Sunosi to Axsome. See Note 15 for further information relating to this transaction.

The gross carrying amounts and net book values of our intangible assets were as follows (in thousands): 
March 31, 2021December 31, 2020 March 31, 2022December 31, 2021
Remaining
Weighted-
Average Useful
Life
(In years)
Gross
Carrying
Amount
Accumulated
Amortization
Net Book
Value
Gross
Carrying
Amount
Accumulated
Amortization
Net Book
Value
Remaining
Weighted-
Average Useful
Life
(In years)
Gross
Carrying
Amount
Accumulated
Amortization
Net Book
Value
Gross
Carrying
Amount
Accumulated
Amortization
Net Book
Value
Acquired developed technologiesAcquired developed technologies12.5$3,326,448 $(1,218,402)$2,108,046 $3,379,162 $(1,184,111)$2,195,051 Acquired developed technologies11.2$7,948,903 $(1,316,734)$6,632,169 $8,195,675 $(1,198,333)$6,997,342 
Manufacturing contractsManufacturing contracts12,551 (12,551)13,135 (13,135)Manufacturing contracts11,883 (11,883)— 12,124 (12,124)— 
TrademarksTrademarks2,903 (2,903)2,917 (2,917)Trademarks2,887 (2,887)— 2,893 (2,893)— 
Total finite-lived intangible assetsTotal finite-lived intangible assets7,963,673 (1,331,504)6,632,169 8,210,692 (1,213,350)6,997,342 
Acquired in-process research and development assetsAcquired in-process research and development assets150,888 — 150,888 154,986 — 154,986 
Total intangible assetsTotal intangible assets$3,341,902 $(1,233,856)$2,108,046 $3,395,214 $(1,200,163)$2,195,051 Total intangible assets$8,114,561 $(1,331,504)$6,783,057 $8,365,678 $(1,213,350)$7,152,328 
The decrease in the gross carrying amount of intangible assets as of March 31, 20212022 compared to December 31, 20202021 primarily reflects the reclassification of the Sunosi intangible asset to assets held for sale as a result of the execution of the definitive agreement to divest Sunosi to Axsome in March 2022, partially offset by the negative impact of foreign currency translation adjustments due to the weakening of thesterling and euro against the U.S. dollar.
The assumptions and estimates used to determine future cash flows and remaining useful lives of our intangible and other long-lived assets are complex and subjective. They can be affected by various factors, including external factors, such as industry and economic trends, and internal factors such as changes in our business strategy and our forecasts for specific product lines.
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Based on finite-lived intangible assets recorded as of March 31, 2021,2022, and assuming the underlying assets will not be impaired and that we will not change the expected lives of the assets, future amortization expenses were estimated as follows (in thousands): 
Year Ending December 31,Year Ending December 31,Estimated Amortization ExpenseYear Ending December 31,Estimated Amortization Expense
2021 (remainder)$152,570 
2022172,486 
2022 (remainder)2022 (remainder)$455,447 
20232023172,486 2023607,262 
20242024172,486 2024607,262 
20252025172,486 2025607,262 
20262026607,262 
ThereafterThereafter1,265,532 Thereafter3,747,674 
TotalTotal$2,108,046 Total$6,632,169 

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8.7. Certain Balance Sheet Items
Property, plant and equipment consisted of the following (in thousands):
March 31,
2021
December 31,
2020
March 31,
2022
December 31,
2021
Construction-in-progressConstruction-in-progress$88,111 $86,511 
Manufacturing equipment and machineryManufacturing equipment and machinery72,387 69,079 
Leasehold improvementsLeasehold improvements$54,155 $54,113 Leasehold improvements65,425 66,318 
Land and buildingsLand and buildings47,440 47,555 Land and buildings63,562 64,008 
Manufacturing equipment and machinery33,096 33,465 
Computer softwareComputer software24,479 22,781 Computer software29,604 25,646 
Computer equipmentComputer equipment16,785 18,749 Computer equipment20,937 16,234 
Furniture and fixturesFurniture and fixtures11,641 11,598 Furniture and fixtures10,302 14,412 
Construction-in-progress6,256 7,262 
SubtotalSubtotal193,852 195,523 Subtotal350,328 342,208 
Less accumulated depreciation and amortizationLess accumulated depreciation and amortization(69,989)(67,588)Less accumulated depreciation and amortization(92,696)(85,371)
Property, plant and equipment, netProperty, plant and equipment, net$123,863 $127,935 Property, plant and equipment, net$257,632 $256,837 
Other current assets consisted of the following (in thousands):
March 31,
2022
December 31,
2021
Deferred charge for income taxes on intercompany profit$205,233 $203,480 
Other38,655 48,912 
Total other current assets$243,888 $252,392 
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Accrued liabilities consisted of the following (in thousands):
March 31,
2021
December 31,
2020
March 31,
2022
December 31,
2021
Rebates and other sales deductionsRebates and other sales deductions$137,337 $127,534 Rebates and other sales deductions$258,649 $215,397 
Employee compensation and benefitsEmployee compensation and benefits81,155 102,601 Employee compensation and benefits126,479 158,870 
Sales returns reserve20,278 18,368 
Royalties17,824 15,230 
Consulting and professional services14,201 6,660 
Current portion of operating lease liabilities14,048 14,457 
Derivative instrument liabilities12,676 3,625 
Inventory-related accruals11,199 9,809 
Clinical trial accrualsClinical trial accruals10,722 9,108 Clinical trial accruals27,741 25,612 
Accrued interestAccrued interest7,539 5,722 Accrued interest21,228 48,640 
Accrued royaltiesAccrued royalties19,441 20,345 
Sales return reserveSales return reserve18,749 15,814 
Inventory-related accrualsInventory-related accruals18,708 16,166 
Consulting and professional servicesConsulting and professional services17,527 22,507 
Current portion of lease liabilitiesCurrent portion of lease liabilities16,155 15,763 
Selling and marketing accrualsSelling and marketing accruals7,304 6,742 Selling and marketing accruals14,666 21,566 
Accrued collaboration expenses4,918 444 
Derivative instrument liabilitiesDerivative instrument liabilities8,418 18,419 
Accrued construction-in-progressAccrued construction-in-progress835 1,119 Accrued construction-in-progress3,978 2,894 
Accrued milestonesAccrued milestones— 25,000 
OtherOther33,999 31,313 Other52,971 59,311 
Total accrued liabilitiesTotal accrued liabilities$374,035 $352,732 Total accrued liabilities$604,710 $666,304 

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9.8. Debt
The following table summarizes the carrying amount of our indebtedness (in thousands):
March 31,
2021
December 31,
2020
March 31,
2022
December 31,
2021
2021 Notes$218,812 $218,812 
Unamortized discount and debt issuance costs on 2021 Notes(3,592)(5,883)
2021 Notes, net215,220 212,929 
2024 Notes2024 Notes575,000 575,000 2024 Notes$575,000 $575,000 
Unamortized discount and debt issuance costs on 2024 Notes(89,519)(95,275)
Unamortized - debt issuance costsUnamortized - debt issuance costs(4,023)(4,401)
Unamortized discount - equity componentUnamortized discount - equity component— (66,836)
2024 Notes, net2024 Notes, net485,481 479,725 2024 Notes, net570,977 503,763 
2026 Notes2026 Notes1,000,000 1,000,000 2026 Notes1,000,000 1,000,000 
Unamortized discount and debt issuance costs on 2026 Notes(172,678)(179,518)
Unamortized - debt issuance costsUnamortized - debt issuance costs(10,879)(11,407)
Unamortized discount - equity componentUnamortized discount - equity component— (139,323)
2026 Notes, net2026 Notes, net827,322 820,482 2026 Notes, net989,121 849,270 
Term loan573,623 581,702 
Secured NotesSecured Notes1,474,346 1,473,810 
Term Loan (1)
Term Loan (1)
2,989,424 3,223,100 
Total debtTotal debt2,101,646 2,094,838 Total debt6,023,868 6,049,943 
Less current portionLess current portion248,613 246,322 Less current portion31,000 31,000 
Total long-term debtTotal long-term debt$1,853,033 $1,848,516 Total long-term debt$5,992,868 $6,018,943 
________________________
(1) In May 2021, we entered into a credit agreement that provided for (i) the Dollar Term Loan, (ii) a seven-year $625.0 million term loan B facility, or the Euro Term Loan, together with the Dollar Term Loan, collectively known as the Term Loan and (iii) a five-year $500.0 million revolving credit facility. In 2021 we made voluntary prepayments on the Euro Term Loan totaling €416.7 million, or $502.0 million, and in March 2022 we repaid the remaining outstanding principal of €208.3 million, or $251.0 million.
Exchangeable Senior Notes Due 2026
In 2020 we completed a private placement of $1.0 billion principal amount of the 2026 Notes. Interest on the 2026 Notes is payable semi-annually in cash in arrears on June 15 and December 15 of each year, beginning on December 15, 2020, at a rate of 2.00% per year. In certain circumstances, we may be required to pay additional amounts as a result of any applicable tax
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withholding or deductions required in respect of payments on the 2026 Notes. The 2026 Notes mature on June 15, 2026, unless earlier exchanged, repurchased or redeemed.
The holders of the 2026 Notes have the ability to require us to repurchase all or a portion of their 2026 Notes for cash in the event we undergo certain fundamental changes, such as specified change of control transactions, our liquidation or dissolution or the delisting of our ordinary shares from any of The New York Stock Exchange, The Nasdaq Global Market, The Nasdaq Global Select Market or The Nasdaq Capital Market (or any of their respective successors). Additionally, the terms and covenants in the indenture related to the 2026 Notes include certain events of default after which the 2026 Notes may be due and payable immediately. Prior to June 15, 2026, we may redeem the 2026 Notes, in whole but not in part, subject to compliance with certain conditions, if we have, or on the next interest payment date would, become obligated to pay to the holder of any 2026 Notes additional amounts as a result of certain tax-related events. We also may redeem the 2026 Notes on or after June 20, 2023 and prior to March 15, 2026, in whole or in part, if the last reported sale price per ordinary share has been at least 130% of the exchange price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which we provide the notice of redemption.
The 2026 Notes are exchangeable at an initial exchange rate of 6.4182 ordinary shares per $1,000 principal amount of 2026 Notes, which is equivalent to an initial exchange price of approximately $155.81 per ordinary share. Upon exchange, the 2026 Notes may be settled in cash, ordinary shares or a combination of cash and ordinary shares, at our election. Our intent and policy is to settle the principal amount of the 2026 Notes in cash upon exchange. The exchange rate will be subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest. In addition, following certain make-whole fundamental changes occurring prior to the maturity date of the 2026 Notes or upon our issuance of a notice of redemption, we will in certain circumstances increase the exchange rate for holders of the 2026 Notes who elect to exchange their 2026 Notes in connection with that make-whole fundamental change or during the related redemption period. Prior to March 15, 2026, the 2026 Notes will be exchangeable only upon satisfaction of certain conditions and during certain periods, and thereafter, at any time until the close of business on the second scheduled trading day immediately preceding the maturity date.
Following the adoption of ASU 2020-06, the 2026 Notes are accounted for as a single liability measured at its amortized cost. The total liability is reflected net of issuance costs of $15.3 million which will be amortized over the term of the 2026 Notes. The effective interest rate of the 2026 Notes is 2.26%. During the three months ended March 31, 2022, we recognized interest expense of $5.5 million, of which $5.0 million related to the contractual coupon rate and $0.5 million related to the amortization of debt issuance costs. Please see Note 1 for further information on the adoption of ASU 2020-06.
Exchangeable Senior Notes Due 2024
In 2017, we completed a private placement of $575.0 million principal amount of 2024 Notes. Interest on the 2024 Notes is payable semi-annually in cash in arrears on February 15 and August 15 of each year, beginning on February 15, 2018, at a rate of 1.50% per year. In certain circumstances, we may be required to pay additional amounts as a result of any applicable tax withholding or deductions required in respect of payments on the 2024 Notes. The 2024 Notes mature on August 15, 2024, unless earlier exchanged, repurchased or redeemed.
The holders of the 2024 Notes have the ability to require us to repurchase all or a portion of their 2024 Notes for cash in the event we undergo certain fundamental changes, such as specified change of control transactions, our liquidation or dissolution or the delisting of our ordinary shares from The Nasdaq Global Select Market. Prior to August 15, 2024, we may redeem the 2024 Notes, in whole but not in part, subject to compliance with certain conditions, if we have, or on the next interest payment date would, become obligated to pay to the holder of any 2024 Notes additional amounts as a result of certain tax-related events. We also may redeem the 2024 Notes on or after August 20, 2021, in whole or in part, if the last reported sale price per ordinary share has been at least 130% of the exchange price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which we provide the notice of redemption.
The 2024 Notes are exchangeable at an initial exchange rate of 4.5659 ordinary shares per $1,000 principal amount of 2024 Notes, which is equivalent to an initial exchange price of approximately $219.02 per ordinary share. Upon exchange, the 2024 Notes may be settled in cash, ordinary shares or a combination of cash and ordinary shares, at our election. Our intent and policy is to settle the principal amount of the 2024 Notes in cash upon exchange. The exchange rate will be subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest. In addition, following certain make-whole fundamental changes occurring prior to the maturity date of the 2024 Notes or upon our issuance of a notice of redemption, we will in certain circumstances increase the exchange rate for holders of the 2024 Notes who elect to exchange their 2024 Notes in connection with that make-whole fundamental change or during the related redemption period. Prior to May 15, 2024, the 2024 Notes will be exchangeable only upon satisfaction of certain conditions and during certain periods, and thereafter, at any time until the close of business on the second scheduled trading day immediately preceding the maturity date.
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Following adoption of ASU 2020-06, the 2024 Notes are accounted for as a single liability measured at its amortized cost. The total liability is reflected net of issuance costs of $11.4 million which will be amortized over the term of the 2024 Notes. The effective interest rate of the 2024 Notes is 1.79%. During the three months ended March 31, 2022, we recognized interest expense of $2.5 million, of which $2.1 million related to the contractual coupon rate and $0.4 million related to the amortization of debt issuance costs. Please see Note 1 for further information on the adoption of ASU 2020-06.
The Exchangeable Senior Notes were issued by Jazz Investments I Limited, or the Issuer, a 100%-owned finance subsidiary of Jazz Pharmaceuticals plc. The Exchangeable Senior Notes are senior unsecured obligations of the Issuer and are fully and unconditionally guaranteed on a senior unsecured basis by Jazz Pharmaceuticals plc. No subsidiary of Jazz Pharmaceuticals plc guaranteed the Exchangeable Senior Notes. Subject to certain local law restrictions on payment of dividends, among other things, and potential negative tax consequences, we are not aware of any significant restrictions on the ability of Jazz Pharmaceuticals plc to obtain funds from the Issuer or Jazz Pharmaceuticals plc’s other subsidiaries by dividend or loan, or any legal or economic restrictions on the ability of the Issuer or Jazz Pharmaceuticals plc’s other subsidiaries to transfer funds to Jazz Pharmaceuticals plc in the form of cash dividends, loans or advances. There is no assurance that in the future such restrictions will not be adopted.
As of March 31, 2021, the carrying values of the equity component of the 2021 Notes, 2024 Notes and the 2026 Notes, net of equity issuance costs, were $114.4 million, $149.8 million and $176.3 million, respectively.
Maturities
Scheduled maturities with respect to our long-term debt principal balances outstanding as of March 31, 20212022 were as follows (in thousands):
Year Ending December 31,Scheduled Long-Term Debt Maturities
2021 (remainder)$243,852 
202233,387 
2023517,494 
2024575,000 
2025
Thereafter1,000,000 
Total$2,369,733 

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10. Leases
The components of the lease expense for the three months ended March 31, 2021 and 2020 were as follows (in thousands):
Three Months Ended
March 31,
Lease Cost20212020
Operating lease cost$5,546 $5,290 
Short-term lease cost1,375 870 
Variable lease cost
Sublease income(157)
Net lease cost$6,922 $6,004 
Supplemental balance sheet information related to operating leases was as follows (in thousands):
LeasesClassificationMarch 31,
2021
December 31,
2020
Assets
Operating lease assetsOperating lease assets$125,738 $129,169 
Liabilities
Current
  Operating lease liabilitiesAccrued liabilities14,048 14,457 
Non-current
  Operating lease liabilitiesOperating lease liabilities, less current portion136,020 140,035 
Total operating lease liabilities$150,068 $154,492 
Lease Term and Discount RateMarch 31,
2021
December 31,
2020
Weighted-average remaining lease term - operating leases (years)8.68.7
Weighted-average discount rate - operating leases5.3 %5.3 %
Supplemental cash flow information related to operating leases was as follows (in thousands):
Three Months Ended
March 31,
20212020
Cash paid for amounts included in the measurement of lease liabilities:
Operating cash outflows from operating leases$6,293 $6,215 
Non-cash operating activities:
Operating lease assets obtained in exchange for new operating lease liabilities$375 $201 

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Maturities of operating lease liabilities were as follows (in thousands):
Year Ending December 31,Year Ending December 31,Operating LeasesYear Ending December 31,Scheduled Long-Term Debt Maturities
2021 (remainder)$16,009 
202222,265 
2022 (remainder)2022 (remainder)$23,250 
2023202322,352 202331,000 
2024202424,192 2024606,000 
2025202518,405 202531,000 
202620261,031,000 
ThereafterThereafter86,495 Thereafter4,429,500 
Total lease payments189,718 
Less imputed interest(39,650)
Present value of lease liabilities$150,068 
TotalTotal$6,151,750 

11.9. Commitments and Contingencies
Indemnification
In the normal course of business, we enter into agreements that contain a variety of representations and warranties and provide for general indemnification, including indemnification associated with product liability or infringement of intellectual property rights. Our exposure under these agreements is unknown because it involves future claims that may be made but have not yet been made against us. To date, we have not paid any claims or been required to defend any action related to these indemnification obligations.
We have agreed to indemnify our executive officers, directors and certain other employees for losses and costs incurred in connection with certain events or occurrences, including advancing money to cover certain costs, subject to certain limitations. The maximum potential amount of future payments we could be required to make under the indemnification obligations is unlimited; however, we maintain insurance policies that may limit our exposure and may enable us to recover a portion of any future amounts paid. Assuming the applicability of coverage, the willingness of the insurer to assume coverage, and subject to certain retention, loss limits and other policy provisions, we believe the fair value of these indemnification obligations is not significant. Accordingly, we did not recognize any liabilities relating to these obligations as of March 31, 20212022 and December 31, 2020.2021. No assurances can be given that the covering insurers will not attempt to dispute the validity, applicability, or amount of coverage without expensive litigation against these insurers, in which case we may incur substantial liabilities as a result of these indemnification obligations.
Other Commitments
As of March 31, 2021,2022, we had $88.8$74.4 million of noncancelable purchase commitments due within one year, primarily related to agreements with third party manufacturers and marketing campaigns.manufacturers.
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Legal Proceedings
We are involved in legal proceedings, including the following matters:
Xyrem Class Action
From June 2020 to March 2021,February 2022, a number of class action lawsuits were filed on behalf of purported direct and indirect Xyrem purchasers, alleging that the patent litigation settlement agreements we entered with Hikma and othergeneric drug manufacturers who had filed Abbreviated New Drug Applications, or ANDA, filers violate state and federal antitrust and consumer protection laws, as follows:
On June 17, 2020, a class action lawsuit was filed in the United States District Court for the Northern District of Illinois by Blue Cross and Blue Shield Association, or BCBS, against Jazz Pharmaceuticals plc, Jazz Pharmaceuticals, Inc., and Jazz Pharmaceuticals Ireland Limited, or, collectively, the Company Defendants (hereinafter referred to as the BCBS Lawsuit). The BCBS Lawsuit also names Roxane Laboratories, Inc., Hikma Pharmaceuticals USA Inc., Eurohealth (USA), Inc., Hikma Pharmaceuticals plc, Amneal Pharmaceuticals LLC, Par Pharmaceuticals, Inc., Lupin Ltd., Lupin Pharmaceuticals Inc., and Lupin Inc., or, collectively, the BCBS Defendants.
On June 18 and June 23, 2020, respectively, 2 additional class action lawsuits were filed against the Company Defendants and the BCBS Defendants: one by the New York State Teamsters Council Health and Hospital Fund in the United States District Court for the Northern District of California, and another by the Government Employees Health Association Inc. in the United States District Court for the Northern District of Illinois (hereinafter referred to as the GEHA Lawsuit).
On June 18, 2020, a class action lawsuit was filed in the United States District Court for the Northern District of California by the City of Providence, Rhode Island, on behalf of itself and all others similarly situated, against Jazz
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Pharmaceuticals plc, and Roxane Laboratories, Inc., West-Ward Pharmaceuticals Corp., Hikma Labs Inc., Hikma Pharmaceuticals USA Inc., and Hikma Pharmaceuticals plc, or, collectively, the City of Providence Defendants.
On June 30, 2020, a class action lawsuit was filed in the United States District Court for the Northern District of Illinois by UFCW Local 1500 Welfare Fund on behalf of itself and all others similarly situated, against Jazz Pharmaceuticals Ireland Ltd., Jazz Pharmaceuticals, Inc., Roxane Laboratories, Inc., Hikma Pharmaceuticals plc, Eurohealth (USA), Inc. and West-Ward Pharmaceuticals Corp., or collectively the UFCW Defendants (hereinafter referred to as the UFCW Lawsuit).
On July 13, 2020, the plaintiffs in the BCBS Lawsuit and the GEHA Lawsuit dismissed their complaints in the United States District Court for the Northern District of Illinois and refiled their respective lawsuits in the United States District Court for the Northern District of California. On July 14, 2020, the plaintiffs in the UFCW Lawsuit dismissed their complaint in the United States District Court for the Northern District of Illinois and on July 15, 2020, refiled their lawsuit in the United States District Court for the Northern District of California.
On July 31, 2020, a class action lawsuit was filed in the United States District Court for the Southern District of New York by the A.F. of L.-A.G.CL.-A.G.C. Building Trades Welfare Plan on behalf of itself and all others similarly situated, against Jazz Pharmaceuticals plc (hereinafter referred to as the AFL Plan Lawsuit). The AFL Plan Lawsuit also names Roxane Laboratories Inc., West-Ward Pharmaceuticals Corp., Hikma Labs Inc., Hikma Pharmaceuticals plc, Amneal Pharmaceuticals LLC, Par Pharmaceuticals Inc., Lupin Ltd., Lupin Pharmaceuticals, Inc., and Lupin Inc.
On August 14, 2020, an additional class action lawsuit was filed in the United States District Court for the Southern District of New York by the Self-Insured Schools of California on behalf of itself and all others similarly situated, against the Company Defendants, as well as Hikma Pharmaceuticals plc, Eurohealth (USA) Inc., Hikma Pharmaceuticals USA, Inc., West-Ward Pharmaceuticals Corp., Roxane Laboratories, Inc., Amneal Pharmaceuticals LLC, Endo International, plc, Endo Pharmaceuticals LLC, Par Pharmaceutical, Inc., Lupin Ltd., Lupin Pharmaceuticals Inc., Lupin Inc., Sun Pharmaceutical Industries Ltd., Sun Pharmaceutical Holdings USA, Inc., Sun Pharmaceutical Industries, Inc., Ranbaxy Laboratories Ltd., Teva Pharmaceutical Industries Ltd., Watson Laboratories, Inc., Wockhardt Ltd., Morton Grove Pharmaceuticals, Inc., Wockhardt USA LLC, Mallinckrodt plc, and Mallinckrodt LLC (hereinafter referred to as the Self-Insured Schools Lawsuit).
On September 16, 2020, an additional class action lawsuit was filed in the United States District Court for the Northern District of California, by Ruth Hollman on behalf of herself and all others similarly situated, against the same defendants named in the Self-Insured Schools Lawsuit.
In December 2020, the above cases were centralized and transferred to the United States District Court for the Northern District of California, where the multidistrict litigation will proceed for the purpose of discovery and pre-trial proceedings. In January 2021, the United States District Court for the Northern District of California issued a Case Management Order that schedules this case for trial in February 2023.
On March 18, 2021, United Healthcare Services, Inc. filed a lawsuit in the United States District Court for the District of Minnesota against the Company Defendants, Hikma Pharmaceuticals plc, Roxane Laboratories, Inc., Hikma Pharmaceuticals USA Inc., Eurohealth (USA) Inc., Amneal Pharmaceuticals LLC, Par Pharmaceutical Inc., Lupin Ltd., and Lupin
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Pharmaceuticals, Inc., raising similar allegations, or the UHS Lawsuit. On March 24, 2021, the U.S. Judicial Panel on Multidistrict Litigation conditionally transferred the UHS Lawsuit to the United States District Court for the Northern District of California, where it was consolidated for discovery and pre-trial proceedings with the other cases.
On August 13, 2021, the United States District Court for the Northern District of California granted in part and denied in part the Company Defendants motion to dismiss the complaints in the cases referenced above.
On October 8, 2021, Humana Inc. filed a lawsuit in the United States District Court for the Northern District of California against the Company Defendants, Hikma Pharmaceuticals plc, Hikma Pharmaceuticals USA Inc., Hikma Labs, Inc., Eurohealth (USA), Inc., Amneal Pharmaceuticals LLC, Par Pharmaceutical, Inc., Lupin Ltd., Lupin Pharmaceuticals, Inc., and Lupin Inc, raising similar allegations.
On October 8, 2021, Molina Healthcare Inc. filed a lawsuit in the United States District Court for the Northern District of California against the Company Defendants, Hikma Pharmaceuticals plc, Hikma Pharmaceuticals USA Inc., Hikma Labs, Inc., Eurohealth (USA), Inc., Amneal Pharmaceuticals LLC, Par Pharmaceutical, Inc., Lupin Ltd., Lupin Pharmaceuticals, Inc., and Lupin Inc, raising similar allegations.
On February 17, 2022, Health Care Service Corporation filed a lawsuit in the United States District Court for the Northern District of California against the Company Defendants, Hikma Pharmaceuticals plc, Hikma Pharmaceuticals USA Inc., Hikma Labs, Inc., Eurohealth (USA), Inc., Amneal Pharmaceuticals LLC, Par Pharmaceutical, Inc., Lupin Ltd., Lupin Pharmaceuticals, Inc., and Lupin Inc, raising similar allegations.
A hearing on class certification is scheduled for November 2022. A trial date will be set following a ruling on class certification.
The plaintiffs in certain of these lawsuits are seeking to represent a class of direct purchasers of Xyrem, and the plaintiffs in the remaining lawsuits are seeking to represent a class of indirect purchasers of Xyrem. Each of the lawsuits generally alleges violations of U.S. federal and state antitrust, consumer protection, and unfair competition laws in connection with the Company Defendants’ conduct related to Xyrem, including actions leading up to, and entering into, patent litigation settlement agreements with each of the other named defendants. Each of the lawsuits seeks monetary damages, exemplary damages, equitable relief against the alleged unlawful conduct, including disgorgement of profits and restitution, and injunctive relief. It is possible that additional lawsuits will be filed against the Company Defendants making similar or related allegations. If the plaintiffs were to be successful in their claims, they may be entitled to injunctive relief or we may be required to pay significant monetary damages, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.
In December 2020, these cases were centralized and transferred to the United States District Court for the Northern District of California, where the multidistrict litigation will proceed for the purpose of discovery and pre-trial proceedings. In January 2021, the Court issued a Case Management Order that schedules this case for trial in February 2023.
On March 18, 2021, United Healthcare Services, Inc. filed a lawsuit in the United States District Court for the District of Minnesota against the Company Defendants, Hikma Pharmaceuticals plc, Roxane Laboratories, Inc., Hikma Pharmaceuticals USA Inc., Eurohealth (USA) Inc., Amneal Pharmaceuticals LLC, Par Pharmaceutical Inc., Lupin Ltd., and Lupin Pharmaceuticals, Inc., raising similar allegations, or the UHS Lawsuit. On March 24, 2021, the U.S. Judicial Panel on MultidistrictGW Acquisition Litigation conditionally transferred the UHS Lawsuit to the United States District Court for the Northern District of California, where it was consolidated for discovery and pre-trial proceedings with the other cases.
On March 15, 2021, GW filed a definitive proxy statement, or Proxy Statement, with the Securities and Exchange Commission in connection with the GW Acquisition.
Since the filing of the Proxy Statement, Jazz Pharmaceuticals plc has been named in 2 lawsuits filed in state and federal courts in New York on March 17, 2021 by purported GW shareholders in connection with the GW Acquisition, theAcquisition. The first was filed in the United States District Court for the Southern District of New York by James Farrell (hereinafter referred to as the Farrell Lawsuit,Lawsuit) and an additional suit was filed in New York state court by Brian Levy or(hereinafter referred to as the Levy Lawsuit.Lawsuit). In addition to Jazz Pharmaceuticals plc, Jazz Pharmaceuticals UKU.K. Holdings Ltd., GW Pharmaceuticals plc, and the GW Board of Directors are named as defendants in the Farrell Lawsuit. In the Levy Lawsuit, GW Pharmaceuticals plc, the GW Board of Directors,
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Centerview Partners LLC, and Goldman Sachs & Co. LLC are named as defendants. In addition to the Farrell Lawsuit and the Levy Lawsuit, 10 additional suits have been filed in New York, California, and Pennsylvania federal courts by purported GW shareholders against GW Pharmaceuticals plc and its Board of Directors, but which do not name any Jazz Pharmaceuticals parties (hereinafter referred to as the GW Litigation, and collectively with the Farrell Lawsuit and the Levy Lawsuit, as the Transaction Litigation.Litigation). In the Transaction Litigation, the plaintiffs allege that the Proxy Statement omitted material information and contained misrepresentations, and that the individual members of the GW Board of Directors breached their fiduciary duties, in violation of state and federal laws, including the Securities Exchange Act of 1934. The plaintiffs in the Transaction Litigation sought various remedies, including injunctive relief to prevent the consummation of the GW Acquisition unless certain allegedly material information was disclosed, or in the alternative, rescission or damages.
On April 14, 2021, GW filed a Form8-K containing supplemental disclosures related to the GW Acquisition. Pursuant to a memorandum of understanding between the parties, the Levy Lawsuit was dismissed on April 14, 2021.
JazzOn May 27, 2021, a class action lawsuit was filed in the United States District Court for the Southern District of California by plaintiff Kurt Ziegler against GW and its former Directors asserting claims under Sections 14(a) and 20(a) of the Securities Exchange Act of 1934, referred to as the Ziegler Lawsuit. The allegations in the Ziegler Lawsuit are similar to those in the previously dismissed Transaction Litigation.
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Patent Infringement Litigation
Avadel Patent Litigation
On May 13, 2021, we filed a patent infringement suit against Avadel Pharmaceuticals plc, or Avadel, and several of its corporate affiliates in the United States District Court for the District of Delaware. The suit alleges that Avadel’s product candidate FT-218 will infringe 5 of our patents related to controlled release formulations of oxybate and the safe and effective distribution of oxybate. The suit seeks an injunction to prevent Avadel from launching a product that would infringe these patents, and an award of monetary damages if Avadel does not believe any of GW’s supplemental disclosures were material or required by law,launch an infringing product. Avadel filed an answer to the complaint and further believescounterclaims asserting that the claimspatents are invalid or not enforceable, and that its product, if approved, will not infringe our patents.
On August 4, 2021, we filed an additional patent infringement suit against Avadel in the Transaction LitigationUnited States District Court for the District of Delaware. The second suit alleges that Avadel’s product candidate FT-218 will infringe a newly-issued patent related to sustained-release formulations of oxybate. The suit seeks an injunction to prevent Avadel from launching a product that would infringe this patent, and an award of monetary damages if Avadel does launch an infringing product. Avadel filed an answer to the complaint and counterclaims asserting that the patents are meritless. Jazzinvalid or not enforceable, and that its product, if approved, will continue to defend itselfnot infringe our patents.
On November 10, 2021, we filed an additional patent infringement suit against Avadel in the remaining Transaction Litigation.United States District Court for the District of Delaware. The third suit alleges that Avadel’s product candidate FT-218 will infringe a newly-issued patent related to sustained-release formulations of oxybate. The suit seeks an injunction to prevent Avadel from launching a product that would infringe this patent, and an award of monetary damages if Avadel does launch an infringing product. Avadel filed an answer to the complaint and counterclaims asserting that the patents are invalid or not enforceable, and that its product, if approved, will not infringe our patents.
On April 14, 2022, Avadel sued us in the United States District Court for the District of Delaware. Avadel’s new suit alleges that we misappropriated trade secrets related to Avadel’s once-nightly sodium oxybate development program and breached certain contracts between the parties. Avadel seeks monetary damages, an injunction preventing us from using Avadel’s confidential information, and an order directing the United States Patent and Trademark Office to modify the inventorship of one of our oxybate patents.
Canopy Patent Litigation
In December 2020, Canopy Growth Corporation filed a complaint against our subsidiary, GW, in the United States District Court for the Western District of Texas, alleging infringement of its patent, U.S. Patent No. 10,870,632. Canopy claims that our extraction process used to produce material used to produce Epidiolex infringes its patent. Canopy seeks a judgment that we have infringed their patent and an award of monetary damages. In July 2021, we filed an answer to the amended complaint, and counterclaims seeking judgment that the ‘632 patent is invalid and that we have not infringed the patent. In October 2021, the United States District Court for the Western District of Texas held a claim construction hearing regarding the disputed term of the ‘632 patent. In November 2021, the Court issued a claim construction order. On February 23, 2022, the parties filed a Joint Motion and Stipulation to Enter Final Judgment in favor of GW. On February 25, 2022, the Court granted the parties’ motion and entered final judgment in favor of GW. Pursuant to the stipulation, Canopy filed a notice of appeal of the Court’s ruling on the disputed term in March 2022.
Lupin Patent Litigation
In June 2021, we received notice from Lupin Inc., or Lupin, that it has filed with FDA an ANDA, for a generic version of Xywav. The notice from Lupin included a “paragraph IV certification” with respect to ten of our patents listed in FDA’s Orange Book for Xywav on the date of our receipt of the notice. The asserted patents relate generally to the composition and method of use of Xywav, and methods of treatment when Xywav is administered concomitantly with certain other medications. A paragraph IV certification is a certification by a generic applicant that alleges that patents covering the branded product are invalid, unenforceable, and/or will not be infringed by the manufacture, use or sale of the generic product.
In July 2021, we filed a patent infringement suit against Lupin in the United States District Court for the District of New Jersey. The complaint alleges that by filing its ANDA, Lupin has infringed 10 of our Orange Book listed patents. We are seeking a permanent injunction to prevent Lupin from introducing a generic version of Xywav that would infringe our patents. As a result of this lawsuit, we expect that a stay of approval of up to 30 months will be imposed by FDA on Lupin's ANDA. In June 2021, FDA recognized seven years of Orphan Drug Exclusivity for Xywav through July 21, 2027. On October4,2021, Lupinfiled an answer to the complaint and counterclaims asserting that the patents are invalid or not enforceable, and that its product, if approved, will not infringe our patents.
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Otsuka Patent Litigation
In October 2021, Otsuka Pharmaceutical Co., Ltd., or Otsuka, filed claims against GW Pharma Limited and GW Pharmaceuticals Limited, or collectively, the GW Parties, in the English High Court, Patents Court. Otsuka alleges that under a now-expired Research Collaboration and License Agreement between Otsuka and the GW Parties, Otsuka and the GW Parties jointly own certain patents and other intellectual property, that Epidiolex is covered by that intellectual property, and that Otsuka is therefore due a royalty on net sales of Epidiolex.
In January 2022, we filed a lawsuit against Otsuka in the Supreme Court of the State of New York, County of New York, seeking a declaration that Otsuka is not entitled to any royalties on sales of Epidiolex under the Research Collaboration and License Agreement.
The Company vigorously enforces its intellectual property rights, but cannot predict the outcome of these matters.
From time to time we are involved in legal proceedings arising in the ordinary course of business. We believe there is no other litigation pending that could have, individually or in the aggregate, a material adverse effect on our results of operations or financial condition.

12.10. Shareholders’ Equity
Share Repurchase Program
In November 2016, our board of directors authorized a share repurchase program and as of March 31, 2021 had authorized the repurchase of ordinary shares having an aggregate purchase price of up to $1.5 billion, exclusive of any brokerage commissions. Under this program, which has no expiration date, we may repurchase ordinary shares from time to time on the open market.  The timing and amount of repurchases will depend on a variety of factors, including the price of our ordinary shares, alternative investment opportunities, restrictions under the amended credit agreement, corporate and regulatory requirements and market conditions. The share repurchase program may be modified, suspended or discontinued at any time without prior notice. During the three months ended March 31, 2021, we did 0t repurchase any of our ordinary shares. As of March 31, 2021, the remaining amount authorized under the share repurchase program was $431.2 million.
Accumulated Other Comprehensive Income (Loss)
The components of accumulated other comprehensive income (loss) as of March 31, 20212022 and December 31, 20202021 were as follows (in thousands): 
Net Unrealized
Loss From
Hedging Activities
Foreign
Currency
Translation
Adjustments
Total
Accumulated
Other
Comprehensive
Loss
Balance at December 31, 2020$(2,467)$(131,885)$(134,352)
Other comprehensive loss before reclassifications(16)(46,220)(46,236)
Amounts reclassified from accumulated other comprehensive loss1,160 1,160 
Other comprehensive income (loss), net1,144 (46,220)(45,076)
Balance at March 31, 2021$(1,323)$(178,105)$(179,428)
Net Unrealized
Loss From
Hedging Activities
Foreign
Currency
Translation
Adjustments
Total
Accumulated
Other
Comprehensive
Loss
Balance at December 31, 2021$(128)$(400,232)$(400,360)
Other comprehensive loss before reclassifications— (190,488)(190,488)
Amounts reclassified from accumulated other comprehensive income (loss)128 — 128 
Other comprehensive income (loss), net128 (190,488)(190,360)
Balance at March 31, 2022$— $(590,720)$(590,720)
During the three months ended March 31, 2021,2022, other comprehensive loss primarily reflects foreign currency translation adjustments, primarily due to the weakening of the sterling and the euro against the U.S. dollar.

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13.11. Net Income (Loss) per Ordinary Share
Basic net income (loss) per ordinary share is based on the weighted-average number of ordinary shares outstanding. Diluted net income (loss) per ordinary share is based on the weighted-average number of ordinary shares outstanding and potentially dilutive ordinary shares outstanding.
Basic and diluted net income (loss) per ordinary share were computed as follows (in thousands, except per share amounts): 
Three Months Ended
March 31,
Three Months Ended
March 31,
2021202020222021
Numerator:Numerator:Numerator:
Net income (loss)$121,832 $(157,833)
Net incomeNet income$1,647 $121,832 
Denominator:Denominator:Denominator:
Weighted-average ordinary shares used in per share calculations - basicWeighted-average ordinary shares used in per share calculations - basic56,468 55,956 Weighted-average ordinary shares used in per share calculations - basic61,865 56,468 
Dilutive effect of employee equity incentive and purchase plansDilutive effect of employee equity incentive and purchase plans1,584 Dilutive effect of employee equity incentive and purchase plans1,042 1,584 
Dilutive effect of Exchangeable Senior NotesDilutive effect of Exchangeable Senior Notes341 Dilutive effect of Exchangeable Senior Notes— 341 
Weighted-average ordinary shares used in per share calculations - dilutedWeighted-average ordinary shares used in per share calculations - diluted58,393 55,956 Weighted-average ordinary shares used in per share calculations - diluted62,907 58,393 
Net income (loss) per ordinary share:
Net income per ordinary share:Net income per ordinary share:
BasicBasic$2.16 $(2.82)Basic$0.03 $2.16 
DilutedDiluted$2.09 $(2.82)Diluted$0.03 $2.09 
Potentially dilutive ordinary shares from our employee equity incentive and purchase plans and the Exchangeable Senior Notes are determined by applying the treasury stock method to the assumed exercise of share options, the assumed vesting of outstanding Restricted Stock Units, or RSUs, and Performance-based restricted stock units, or RSUs,PRSUs, and the assumed issuance of ordinary shares under our employee stock purchase plan, or ESPP, andESPP. Potentially dilutive ordinary shares from the Exchangeable Senior Notes are determined by applying the if-converted method to the assumed issuance of ordinary shares upon exchange of the Exchangeable Senior Notes. The potential issue of ordinary shares issuable upon exchange of the Exchangeable Senior Notes was anti-dilutive and had no effectimpact on diluted net income (loss) per ordinary share for the three months ended March 31, 2020 because the average price of our ordinary shares for the three months ended March 31, 2020 did not exceed the effective exchange prices per ordinary share of the Exchangeable Senior Notes.2022.
The following table represents the weighted-average ordinary shares that were excluded from the calculation of diluted net income (loss) per ordinary share for the periods presented because including them would have an anti-dilutive effect (in thousands): 
Three Months Ended
March 31,
Three Months Ended
March 31,
20212020 20222021
Exchangeable Senior NotesExchangeable Senior Notes9,798 5,504 Exchangeable Senior Notes9,044 9,798 
Options, RSUs and ESPP1,671 5,611 
Employee equity incentive and purchase plansEmployee equity incentive and purchase plans2,509 1,671 

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14.12. Revenues
The following table presents a summary of total revenues (in thousands): 
Three Months Ended
March 31,
Three Months Ended
March 31,
2021202020222021
XyremXyrem$335,550 $407,875 Xyrem$247,497 $335,550 
XywavXywav75,416 Xywav186,080 75,416 
Total OxybateTotal Oxybate410,966 407,875  Total Oxybate433,577 410,966 
Epidiolex/EpidyolexEpidiolex/Epidyolex157,893 — 
SunosiSunosi11,606 1,924 Sunosi15,878 11,606 
SativexSativex4,742 — 
Total NeuroscienceTotal Neuroscience422,572 409,799 Total Neuroscience612,090 422,572 
ZepzelcaZepzelca54,334 Zepzelca59,338 54,334 
RylazeRylaze54,220 — 
VyxeosVyxeos33,155 32,720 Vyxeos33,757 33,155 
Defitelio/defibrotideDefitelio/defibrotide49,619 47,432 Defitelio/defibrotide49,489 49,619 
Erwinaze/ErwinaseErwinaze/Erwinase41,068 37,732 Erwinaze/Erwinase— 41,068 
Total OncologyTotal Oncology178,176 117,884 Total Oncology196,804 178,176 
OtherOther2,783 2,522 Other943 2,783 
Product sales, netProduct sales, net603,531 530,205 Product sales, net809,837 603,531 
Royalties and contract revenuesRoyalties and contract revenues4,050 4,521 Royalties and contract revenues3,884 4,050 
Total revenuesTotal revenues$607,581 $534,726 Total revenues$813,721 $607,581 
The following table presents a summary of total revenues attributed to geographic sources (in thousands): 
Three Months Ended
March 31,
Three Months Ended
March 31,
2021202020222021
United StatesUnited States$548,292 $477,789 United States$740,583 $548,292 
EuropeEurope47,233 41,556 Europe61,028 47,233 
All otherAll other12,056 15,381 All other12,110 12,056 
Total revenuesTotal revenues$607,581 $534,726 Total revenues$813,721 $607,581 
The following table presents a summary of the percentage of total revenues from customers that represented more than 10% of our total revenues: 
Three Months Ended
March 31,
Three Months Ended
March 31,
2021202020222021
ESSDSESSDS67 %76 %ESSDS55 %67 %
McKessonMcKesson14 %13 %McKesson12 %14 %
Financing and payment
Our payment terms vary by the type and location of our customer but payment is generally required in a term ranging from 30 to 45 days.
Contract Liabilities - Deferred Revenue
The deferred revenue balance as of March 31, 20212022 primarily related to deferred upfront fees received from Nippon Shinyaku Co., Ltd., or Nippon Shinyaku, in connection with 2 license, development and commercialization agreements granting Nippon Shinyaku exclusive rights to develop and commercialize each of Defitelio and Vyxeos in Japan. We recognized contract revenues of $0.6$0.5 million during the three months ended March 31, 2021,2022, relating to these upfront payments.
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The deferred revenue balances are being recognized over an average of four years representing the period over which we expect to perform our research and developments obligations under each agreement.
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The following table presents a reconciliation of our beginning and ending balances in contract liabilities from contracts with customers for the three months ended March 31, 20212022 (in thousands): 
Contract Liabilities
Balance as of December 31, 20202021$4,8612,556 
Amount recognized within royalties and contract revenues(636)(523)
Balance as of March 31, 20212022$4,2252,033 

15.13. Share-Based Compensation
Share-based compensation expense related to share options, RSUs, PRSUs and grants under our ESPP was as follows (in thousands): 
Three Months Ended
March 31,
Three Months Ended
March 31,
2021202020222021
Selling, general and administrativeSelling, general and administrative$23,846 $20,596 Selling, general and administrative$34,785 $23,846 
Research and developmentResearch and development8,643 6,385 Research and development12,436 8,643 
Cost of product salesCost of product sales1,996 1,673 Cost of product sales2,849 1,996 
Total share-based compensation expense, pre-taxTotal share-based compensation expense, pre-tax34,485 28,654 Total share-based compensation expense, pre-tax50,070 34,485 
Income tax benefit from share-based compensation expenseIncome tax benefit from share-based compensation expense(6,587)(3,121)Income tax benefit from share-based compensation expense(8,823)(6,753)
Total share-based compensation expense, net of taxTotal share-based compensation expense, net of tax$27,898 $25,533 Total share-based compensation expense, net of tax$41,247 $27,732 
Share Options
There were no share options granted in the three months ended March 31, 2022. The table below shows the number of shares underlying options granted to purchase our ordinary shares, the weighted-average assumptions used in the Black-Scholes option pricing model and the resulting weighted-average grant date fair value of share options granted:granted for the three months ended March 31, 2021: 
Three Months Ended
March 31,
20212020
Shares underlying options granted (in thousands)95 565 
Grant date fair value$51.33 $33.65 
Black-Scholes option pricing model assumption information:
Volatility37 %32 %
Expected term (years)4.54.6
Range of risk-free rates0.4-0.8%0.8-1.6%
Expected dividend yield%%
Three Months Ended
March 31, 2021
Shares underlying options granted (in thousands)95 
Grant date fair value$51.33 
Black-Scholes option pricing model assumption information:
Volatility37 %
Expected term (years)4.5
Range of risk-free rates0.4%-0.8%
Expected dividend yield— %
Restricted Stock Units
The table below shows the number of RSUs granted covering an equal number of our ordinary shares and the weighted-average grant date fair value of RSUs granted:
Three Months Ended
March 31,
Three Months Ended
March 31,
2021202020222021
RSUs granted (in thousands)RSUs granted (in thousands)1,201 959 RSUs granted (in thousands)1,888 1,201 
Grant date fair valueGrant date fair value$169.87 $114.19 Grant date fair value$152.38 $169.87 
The fair value of RSUs is determined on the date of grant based on the market price of our ordinary shares on that date. The fair value of RSUs is expensed ratably over the vesting period, generally over four years.
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Performance-Based Restricted Stock Units
In March 2022, the Compensation & Management Development Committee of our board of directors approved awards of PRSUs to certain employees of the Company, subject to vesting on the achievement of certain commercial and pipeline performance criteria to be assessed over a performance period from the date of the grant to December 31, 2024. Following the determination of the Company’s achievement with respect to the performance criteria, the amount of shares awarded will be subject to adjustment based on the application of a relative total shareholder return, or TSR modifier. The number of shares that may be earned ranges between 0% and 200% of the target number of PRSUs granted based on the degree of achievement of the applicable performance metric and the application of the relative TSR modifier.
The table below shows the number of PRSUs granted covering an equal number of our ordinary shares and the weighted-average grant date fair value of PRSUs granted:
Three Months Ended
March 31, 2022
PRSUs granted (in thousands)281 
Grant date fair value$179.19 
As the PRSUs granted in March 2022 are subject to a market condition, the grant date fair value for such PRSUs was based on a Monte Carlo simulation model. The Company evaluated the performance targets in the context of its current long-range financial plan and its product candidate development pipeline and recognized expense based on the probable number of awards that will ultimately vest. There were no PRSUs granted in the three months ended March 31, 2021.
As of March 31, 2021,2022, compensation cost not yet recognized related to unvested share options, RSUs and RSUsPRSUs was $52.0$29.7 million, $418.8 million and $275.1$56.6 million, respectively, which is expected to be recognized over a weighted-average period of 2.21.6 years, 3.2 years and 3.22.3 years, respectively.
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16.14. Income Taxes
Our income tax provisionexpense was $18.0$0.5 million in the three months ended March 31, 2021, compared to an income tax benefit of $51.3 million for the same period in 2020. The effective tax rate was 13.3% in the three months ended March 31, 2021 compared to 24.5% for the same period in 2020. The decrease in the effective tax rate for the three months ended March 31, 20212022, compared to $18.0 million for the same period in 2020 was2021. The decrease in the income tax expense resulted primarily due tofrom the impactmix of the defibrotide acquired in-process researchpre-tax income and development, or IPR&D, asset impairment charge and the acquired IPR&D expense relating to the $200.0 million upfront payment to Pharma Mar, S.A., or PharmaMar, for the exclusive U.S. commercialization and development rights to Zepzelca in 2020, and changes in income mix among the various jurisdictions in which we operate. The effectivelosses incurred across tax rate for the three months ended March 31, 2021 was higher than the Irish statutory rate of 12.5% primarily due to the impact of various expenses not deductible for tax purposes, income taxable at a rate higher than the Irish statutory rate and uncertain tax positions, partially offset by deductions available in respect of subsidiary equity and originating tax credits.jurisdictions. We do not provide for Irish income taxes on undistributed earnings of our foreign operations that are intended to be indefinitely reinvested in our foreign subsidiaries.
Our net deferred tax assetliability is comprised primarily related to acquired intangible assets, and is net of deferred tax assets related to U.S. federal and state tax credits, U.S. federal and state and foreign net operating loss carryforwards and other temporary differences, and is net of deferred tax liabilities related to acquired intangible assets.differences. We maintain a valuation allowance against certain foreign and U.S. deferred tax assets. Each reporting period, we evaluate the need for a valuation allowance on our deferred tax assets by jurisdiction and adjust our estimates as more information becomes available.
We are required to recognize the financial statement effects of a tax position when it is more likely than not, based on the technical merits, that the position will be sustained upon examination. As a result, we have recorded an unrecognized tax benefit for certain tax benefits which we judge may not be sustained upon examination. Our most significant tax jurisdictions are Ireland, and the U.S. (both at the federal level and in various state jurisdictions). For and the U.K. In Ireland we are no longer subject to income tax audits by taxing authorities for the years prior to 2016.2017. The U.S. jurisdictions generally have statute of limitations three to four years from the later of the return due date or the date when the return was filed. However, in the U.S. (at the federal level and in most states), carryforwards that were generated in 20162017 and earlier may still be adjusted upon examination by the tax authorities. DuringIn the three months ended March 31, 2021, certain of our subsidiaries were under examinationU.K. we are no longer subject to income tax audits by the French taxtaxing authorities for the years ended December31,2012, 2013 and 2015 through 2019. Dueprior to the subjective nature of the transfer pricing issues involved, the Company reached an agreement with the French tax authorities to settle the audits for all open years. The settlement agreement in respect of 2012 and 2013 has been finalized and the Company paid incremental taxes, interest and penalties of $18.6 million during the three months ended March 31, 2021 to close the audit of those periods. Settlements in respect of 2015 through 2019 are also expected to be finalized and paid in 2021, and $1.1 million has been accrued in this respect.2018. Certain of our Italian subsidiaries are currently under examination by the Italian taxtaxing authorities for the year ended December31,2017. Certain of our Luxembourg subsidiaries are currently under examination by the Luxembourg taxtaxing authorities for the years ended December31,2017 and 2018. OurCertain of our German subsidiary issubsidiaries are currently under examination by the German taxtaxing authorities for the years ended December 31, 2017, 2018 and 2019.

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17. Subsequent Event15. Assets Held for Sale
Pending GW AcquisitionOn March 25, 2022, we entered into a definitive agreement to divest Sunosi to Axsome. Under the terms of the agreement, Axsome will acquire the rights to Sunosi in all of the existing territories available to us. We will receive a upfront payment of $53 million, a high single-digit royalty on Axsome’s U.S. net sales of Sunosi in current indications and a mid-single-digit royalty on Axsome’s U.S. net sales of Sunosi in future indications.
The respective obligations of GWJazz and usAxsome to consummate the GW Acquisitiontransactions contemplated by the definitive agreement are subject to the satisfaction or waiver of a number of customary conditions, including obtaining certain regulatory approvalsconditions.
The transaction is structured to be completed in sequential closings for the U.S. and obtaining sanction of the Scheme of Arrangement by the High Court of Justice of England and Wales. Certain conditions have been satisfied, including expiration of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 and the approval by GW’s shareholders of the Scheme of Arrangement. The GW Acquisition is not subject to approval by our shareholders, nor is the GW Acquisition subject to a financing contingency. The GW Acquisition is expected to close in the first half of May 2021, subjectex-U.S. territories. Subject to the satisfaction or waiver of the closing conditions, set forththe companies expect the U.S. transaction to close in the GW Transaction Agreement.
On February 3, 2021, in connection withsecond quarter of 2022 and the executionex-U.S. transaction close to occur within 60 days following the close of the GW Transaction Agreement,U.S. transaction.
The assets to be divested met the assets held for sale criteria and were reclassified to assets held for sale as of March 31, 2022. We determined this is the disposal of a business and have allocated goodwill to these assets using the relative fair value method.
We have determined that the expected disposition of these assets does not qualify for reporting as a discontinued operation since the expected sale does not represent a strategic shift that has or will have a major effect on our operations and financial results.
The following assets were segregated and classified as assets held for sale in the condensed consolidated balance sheet (in thousands):

March 31, 2022
Intangible assets, net$56,680 
Inventories21,163 
Goodwill12,927 
Other118 
Total assets held for sale$90,888 
We will account for the contingent consideration in the form of the future royalty as earned. As a result, we expect to record a loss on disposal of approximately $40.0 million when the transaction closes as the determination of the initial gain or loss will include the upfront consideration only and not include an amount for the contingent consideration.

16. Subsequent Events
In the second quarter of 2022, we acquired development and commercialization rights to 2 preclinical compounds, consistent with our objective to expand our pipeline.
In April 2022, we announced that we had entered into a commitment letterlicensing agreement with BofA Securities,Werewolf Therapeutics, Inc., Bankor Werewolf, to acquire exclusive global development and commercialization rights to Werewolf's investigational WTX-613, now referred to as JZP898. JZP898 is a differentiated, conditionally-activated interferon alpha (IFNα) INDUKINE™ molecule. Under the terms of America, N.A.the agreement, we made an upfront payment of $15.0 million to Werewolf, and JPMorgan Chase Bank, N.A. pursuantWerewolf is eligible to which these commitment parties have committed to provide us with a senior secured revolving credit facility in an aggregate principal amountreceive development, regulatory and commercial milestone payments of up to $500.0$1.26 billion. Pending approval, Werewolf is eligible to receive a tiered, mid-single-digit percentage royalty on net sales of JZP898. The upfront payment totaling $15.0 million will be expensed to Acquired in-process research and development, or IPR&D, in the second quarter of 2022.
In May 2022, we announced that we had entered into a senior secured term loan B facilitylicensing agreement with Sumitomo Pharma Co., Ltd, or Sumitomo, to acquire exclusive development and commercialization rights in the United States, Europe and other territories for DSP-0187, which we have designated JZP441. JZP441 is a potent, highly selective oral orexin-2 receptor agonist with potential application for the treatment of narcolepsy, IH and other sleep disorders. Under the terms of the agreement, we will make an aggregate principal amountupfront payment of $50.0 million to Sumitomo, and Sumitomo is eligible to receive development, regulatory and commercial milestone payments of up to $3.15 billion and$1.09 billion. Pending approval, Sumitomo is eligible to receive a senior secured bridge loan facility in an aggregate principal amounttiered, low double-digit royalty on Jazz's net sales of up to $2.2 billion to, among other things, finance our obligations in respect of the GW Acquisition.JZP441. The effectiveness of such credit facilities is subject to the occurrence of customary closing conditions, including the consummation of the GW Acquisition.
On April 20, 2021, we and certain of our wholly-owned subsidiaries, entered into Amendment No. 3 to our Credit Agreement, dated as of June 18, 2015, or the Existing Credit Agreement, with the lenders party thereto and Bank of America, N.A., as administrative agent, collateral agent, letter of credit issuer and swing line lender. The Amendment No. 3 amended the Existing Credit Agreement to permit the issuance of senior secured notes and made certain related changes as set forth therein.
On April 29, 2021, our wholly-owned subsidiary, Jazz Securities Designated Activity Company, issued $1.5 billion in aggregate principal amount of 4.375% senior secured notes due 2029.
Concurrently with the closing of the GW Acquisition, we expect to enter into new senior secured credit facilities, which is expected to consist of a $500.0upfront payment totaling $50.0 million revolving credit facility and a term loan B facility in an aggregate amount of approximately $3.85 billion. We expect to use term loan B borrowings under new senior secured credit facilities and the net proceeds from the senior secured notes, together with cash on hand to fund the cash consideration payable in connection with the GW Acquisition. The senior secured notes have a mandatory redemption clause that will be triggered under certain circumstances, including failureexpensed to complete the GW Acquisition within the time period outlinedAcquired IPR&D in the GW Transaction Agreement or the terminationsecond quarter of the GW Acquisition.2022.

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Item 2.Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion of our financial condition and results of operations should be read in conjunction with the condensed consolidated financial statements and the notes to condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q.10‑Q. This discussion contains forward-looking statements that involve risks and uncertainties. When reviewing the discussion below, you should keep in mind the substantial risks and uncertainties that could impact our business. In particular, we encourage you to review the risks and uncertainties summarized under “Cautionary Note Regarding Forward-Looking Statements” that appears at the end of this discussion and as discusseddescribed in more detail under “Risk Factors” in Part I, Item 1A of our Annual Report on Form 10-K for the year ended December 31, 2020.2021. These risks and uncertainties could cause actual results to differ materially from those projected in forward-looking statements contained in this report or implied by past results and trends. Forward-looking statements are statements that attempt to forecast or anticipate future developments in our business, financial condition or results of operations. See the “Cautionary Note Regarding Forward-Looking Statements” that appears at the end of this discussion. These statements, like all statements in this report, speak only as of the date of this Quarterly Report on Form 10-Q10‑Q (unless another date is indicated), and we undertake no obligation to update or revise these statements in light of future developments.
Overview
Jazz Pharmaceuticals plc is an innovativea global biopharmaceutical company dedicatedwhose purpose is to developing and commercializing life-changing medicines thatinnovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases - often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, infrom early- to late-stage development, across key therapeutic areas. Our focus is in neuroscience including sleep and movement disorders, and in oncology, including hematologic malignancies and solid tumors. We actively exploreoncology. Within these therapeutic areas, we strive to identify new options for patients including novel compounds,by actively exploring small molecules and biologics, and through innovative delivery technologies.technologies and cannabinoid science.
Our continuedstrategy for growth is rooted in executing commercial launches;launches and ongoing commercialization initiatives; advancing robust research and development, or R&D, programs and delivering positiveimpactful clinical results; effectively deploying capital to strengthen the prospects of achieving our short- and long-term goals through strategic and capital-efficient corporate development; and delivering strong financial performance.
In our core therapeutic areas, we follow a similar approach to bring new medicines to patients and to create sustainable shareholder value. Most critically, we We focus on patient populations with high unmet needs. We identify and develop differentiated therapies for these patients that we expect will be long-lived assets and that we can support with an efficient sales force and that we expect will be long-lived, durable assets.commercialization model. In addition, we leverage our efficient, scalable operating model and integrated capabilities andacross our global infrastructure to effectively reach patients around the world.
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TableAt the 40th Annual J.P. Morgan Healthcare Conference in January 2022, we announced our Vision 2025, which aims to deliver sustainable growth and enhanced value, driving our continued transformation to an innovative, high-growth global pharmaceutical leader. The three core components of Contents
our Vision 2025 focus on commercial execution, pipeline productivity and operational excellence.
Commercial Achievements
Our marketed products are approved in countries around the world to improve patient care.
ProductIndicationsInitial U.S. Approval DateMarkets
NEUROSCIENCE
Xywav™Xywav® (calcium, magnesium, potassium, and sodium oxybates)
Treatment of cataplexy or excessive daytime sleepiness, or EDS, in patients seven years of age and older with narcolepsy.


Treatment of idiopathic hypersomnia, or IH, in adults.
July 2020




August 2021

U.S.




U.S.
Xyrem® (sodium oxybate)
Treatment of cataplexy or EDS in patients seven years of age and older with narcolepsy.

For the treatment of cataplexy in patients with narcolepsy.

Treatment of narcolepsy with cataplexy in adult patients, adolescents and children from age of 7 years.

July 2002


August 2005




October 2005
July 2002
U.S.


Canada



EU, Great Britain, other markets (through licensing agreement)
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Epidiolex® (cannabidiol)






Epidyolex® (cannabidiol)
Treatment of seizures associated with Lennox-Gastaut syndrome, or LGS, Dravet syndrome, or DS, or tuberous sclerosis complex, or TSC, in patients 1 year of age and older.

For adjunctive therapy of seizures associated with LGS or DS, in conjunction with clobazam, for patients 2 years of age and older.*

For adjunctive therapy of seizures associated with TSC for patients 2 years of age and older.**


June 2018





September 2019



April 2021

U.S., Other Markets





EU, Great Britain, other markets


EU, Great Britain, other markets
Sunosi® (solriamfetol)***
Improve wakefulness in adult patients with EDS associated with narcolepsy or obstructive sleep apnea, or OSA.

Improve wakefulness and reduce EDS in adult patients with narcolepsy (with or without cataplexy) or adult patients with OSA whose EDS has not been satisfactorily treated by primary OSA therapy, such as continuous positive airway pressure, or CPAP.

Treatment of EDS in adult patients with narcolepsy or OSA.
March 2019





January 2020





May 2021

U.S., Europe, United Kingdom (UK)





EU, Great Britain, other markets




Canada
Sativex® (nabiximols)
Treatment for adult patients with moderate to severe spasticity due to multiple sclerosis, or MS, who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy.June 2010U.K. (other markets through licensing agreements with partners)
ONCOLOGY
Zepzelca™Zepzelca® (lurbinectedin)
Treatment of adult patients with metastatic small cell lung cancer, or SCLC, with disease progression on or after platinum-based chemotherapy.

Treatment of adults with Stage III or metastatic SCLC who have progressed on or after platinum-containing therapy.
June 2020



September 2021
U.S. (licensed from Pharma Mar, S.A.,PharmaMar)


Canada (licensed from PharmaMar)
Rylaze® (asparaginase erwinia chrysanthemi (recombinant)-
rywn)
A component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia, or PharmaMar)ALL, and lymphoblastic lymphoma, or LBL, in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.
June 2021U.S.
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Vyxeos® (daunorubicin and cytarabine) liposome for injection (U.S.)




Vyxeos® liposomal 44 mg/100 mg powder for concentrate for solution for infusion (Europe)

Vyxeos® Daunorubicin and cytarabine liposome for injection Powder, 44 mg daunorubicin and 100 mg cytarabine per vial, intravenous infusion
Newly-diagnosed
Treatment of newly-diagnosed therapy-related therapy-related acute myeloid leukemia, (t-AML)or t-AML or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients one year and older.

Adults
Treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML)t-AML or AML with myelodysplasia-related changes (AML-MRC).
August 2017U.S.




Europe, UK
Defitelio® (defibrotide sodium) (U.S.)AML-MRC.



Treatment of adults with newly diagnosed therapy-related t-AML or AML with AML-MRC.


August 2017




August 2018





April 2021


U.S.




EU, Great Britain, other markets




Canada
Defitelio® (defibrotide sodium)





Defitelio® (defibrotide)


Defitelio® (defibrotide) (Europe)
Treatment of adult and pediatric patients with hepatic veno-occlusive disease, or VOD, also known as sinusoidal obstruction syndrome, or SOS, with renal or pulmonary dysfunction following hematopoietic stem-cellstem cell transplantation, or HSCT.

Treatment of severe hepatic VOD, also known as SOS, infollowing HSCT therapy.


March 2016




October 2013


U.S., Europe, UK, Japan, and




EU, Great Britain, other markets
Erwinaze® (asparaginase Erwinia chrysanthemi)
Treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase.November 2011U.S., Europe, Other Markets
*Clobazam restriction limited to EU and Great Britain
**TSC approval pending in certain markets
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***In March 2022, we announced that we had entered into a definitive agreement to divest Sunosi to Axsome Therapeutics, or Axsome
Neuroscience
We are the global leader in the development and commercialization of oxybate therapy for patients with sleep disorders. We introduced Xyrem was approved by the U.S. Food and Drug Administration, or FDA, in 2002, whichand has become a standard of care for treating EDS and cataplexy in narcolepsy. In 2020, we received U.S. Food and Drug Administration, or FDA approval for Xywav for the treatment of cataplexy or EDS, in patients seven years of age and older with narcolepsy. In August 2021, Xywav became the first and only therapy approved by FDA for the treatment of IH in adults. Xywav is an oxybate therapy that contains 92% less sodium than Xyrem.
Since there is no cure for narcolepsy and long-term disease management is needed, we believe that Xywav represents an important new therapeutic option for patients.patients with this sleep disorder. Our commercial efforts are focused on educating patients and physicians about the lifelong impact of high sodium intake, and how the use of Xywav enables them to address what is a modifiable risk factor.
In June 2021, FDA recognized seven years of Orphan Drug Exclusivity (ODE) for Xywav in narcolepsy. ODE extends through July 2027. In connection with granting ODE, FDA stated that "Xywav is clinically superior to Xyrem by means of greater safety because Xywav provides a greatly reduced chronic sodium burden compared to Xyrem." FDA's summary also stated that "the differences in the sodium content of the two products at the recommended doses will be clinically meaningful in reducing cardiovascular morbidity in a substantial proportion of patients for whom the drug is indicated."
We have seen strongview the adoption of Xywav since its launch in November 2020. In the first quarter of 2021, there were 15,700 average active oxybate patients; exiting the quarter, there were 3,900 active Xywav patients. This increased from 1,900 active Xywav patients exiting the fourth quarter of 2020. We view thisnarcolepsy as a positive indication that physicians and patients appreciate the benefits of a lower-sodiumlower sodium oxybate option. We are seeing strongcontinue to see Xywav adoption among both existing and new-to-oxybate narcolepsy patients.
Coupled with strong adoption, we have met our goal to obtain broad payer coverage for Xywav within six months of launch. We now have agreements in place for Xywav with all three major pharmacy benefit managers, (PBMs)or PBMs, in the U.S. Commercial payerTo date, we have entered into agreements with various entities and have achieved benefit coverage overallfor Xywav for approximately 90% of commercial lives.
On August 12, 2021, FDA approved Xywav for the treatment of IH in adults. Xywav is currently atthe first and only FDA-approved therapy to treat IH. We initiated the U.S. commercial launch of Xywav for the treatment of IH in adults on November 1, 2021. IH is a debilitating neurologic sleep disorder characterized by chronic EDS, the inability to stay awake and alert during the day resulting in the irrepressible need to sleep or unplanned lapses into sleep or drowsiness. An estimated 37,000 people in the U.S. have been diagnosed with IH and are actively seeking healthcare.
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We have seen strong adoption of Xywav in narcolepsy since its launch in November 2020. Exiting the first quarter of 2022, there were approximately 80%7,800 patients taking Xywav, including approximately 7,050 patients with narcolepsy and approximately 750 patients with IH. With respect to Xywav and Xyrem in the aggregate, the average number of covered lives, and our team is working with payers to further expand coverage.active oxybate patients on therapy was approximately 16,650 in the first quarter of 2022.
Sunosi was launched in the United StatesU.S. in 2019 as a therapy to improve wakefulness in adult patients with EDS associated with narcolepsy or OSA, and we remain focused on driving the next phase of its growth. We have established broad commercial payer coverage and have invested in an expanded and dedicated sales force and direct-to-consumer initiatives to raise awareness of EDS due to narcolepsy or OSA. Sunosi was approved in Europe and the United Kingdom in 2020, and the rolling launch is ongoing. Sunosi was approved in Canada in 2021. In March 2022, we announced that we had entered into a definitive agreement to divest Sunosi to Axsome. Under the terms of the agreement, Axsome will receive the rights to Sunosi in all of the existing territories available to us and we will receive an upfront payment of $53 million, a high single-digit royalty on Axsome’s U.S. net sales of Sunosi in current indications and a mid-single-digit royalty on Axsome’s U.S. net sales of Sunosi in future indications. The divestiture of Sunosi to Axsome is intended to enable us to sharpen our focus on our highest strategic priorities designed to deliver sustainable growth and enhanced shareholder value. In assessing the positioning of Sunosi in the overall treatment landscape, we believe that Axsome is well positioned to deliver access to this important medicine and to maximize the value of Sunosi to us through future growth. The respective obligations of the companies to consummate the transactions contemplated by the definitive agreement are pleasedsubject to the satisfaction or waiver of a number of customary conditions. The transaction is structured to be completed in sequential closings for the U.S. and ex-U.S. territories. Subject to the satisfaction or waiver of the closing conditions, the companies expect the U.S. transaction to close in the second quarter of 2022 and the ex-U.S. transaction close to occur within 60 days following the close of the U.S. transaction.
We acquired Epidiolex (Epidyolex outside the U.S.) in May 2021 as part of the acquisition of GW Pharmaceuticals plc, or GW, which we refer to as the GW Acquisition, which expands our growing neuroscience business with a global, high-growth childhood-onset epilepsy franchise. Epidiolex was approved in the progressionU.S. in June 2018 for the treatment of ourseizures associated with two rare and severe forms of epilepsy, LGS and DS, in patients two years of age and older, and subsequently approved in July 2020 for the treatment of seizures associated with TSC in patients one year of age and older. FDA also approved the expansion of all existing indications, LGS and DS, to patients one year of age and older. The rolling launch.European launch of Epidyolex is also underway following European Commission approval in September 2019 for use as adjunctive therapy of seizures associated with LGS or DS, in conjunction with clobazam, for patients two years of age and older. The clobazam restriction is limited to EU and Great Britain. Outside the U.S. and Europe, Epidiolex/Epidyolex is approved in Israel and Australia.
Sativex (nabiximols) is approved in more than 25 countries outside the U.S. for the treatment of adult patients with moderate to severe spasticity due to MS who have not responded adequately to other anti-spasticity medication. We market Sativex directly in the U.K. and through licensing agreements with partners across other countries. We are working toward potential approval of nabiximols in the U.S. with multiple Phase 3 clinical trials in progress.
Oncology
We acquired U.S. development and commercialization rights to Zepzelca in early 2020, and launched six months thereafter with an indication for treatment of patients with SCLC with disease progression on or after platinum-based chemotherapy. Our education and promotional efforts are focused on SCLC-treating physicians. We are seeing increasedcontinuing to raise awareness of Zepzelca across academic and community cancer centers and see continued opportunities for growth in the second-line setting in both platinum-sensitiveshare and platinum-resistant patients,overall demand, reflecting the significant unmet need and favorable Zepzelca product profile. In collaboration with F. Hoffmann-La Roche Ltd (Roche), we have initiated a Phase 3 pivotal clinical trial in first-line extensive stage SCLC of Zepzelca in combination with Tecentriq® (atezolizumab). We are also developing Zepzelca in additional indications.
Rylaze was approved by FDA in June 2021 under the Real-Time Oncology Review (RTOR) program, and was launched in the U.S. in July 2021 for use as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with ALL or LBL in pediatric and adult patients one month and older who have developed hypersensitivity to E. coli-derived asparaginase. Rylaze is the only recombinant erwinia asparaginase manufactured product that maintains a clinically meaningful level of asparaginase activity throughout the entire duration of treatment. We developed Rylaze to address the needs of patients and health care providers for an innovative, high-quality erwinia asparaginase with reliable supply. The current indication is for an intramuscular (IM) dosing regimen of 25 mg/m2 every 48 hours. We submitted a supplemental Biologics License Application (sBLA) with additional data in support of a Monday/Wednesday/Friday (M/W/F) IM dosing schedule in January 2022 and submitted a separate sBLA for intravenous administration in April 2022, both which have been granted review under the RTOR program. We anticipate that data from the current development program will support regulatory filings in Europe in mid-2022, with potential for approval in 2023. The Company is also working with a partner for potential submission, approval and launch in Japan, as well as planning additional submissions in other markets.
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Vyxeos is a treatment for adults with newly-diagnosed therapy-related AML,t-AML, or AML with myelodysplasia-related changes.AML-MRC. In March 2021, FDA approved a revised label to include a new indication to treat newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes in pediatric patients aged one year and older. We have a number of ongoing development activities and continue to expand into new markets internationally. Despite an ongoing trend in the U.S.towards lower-intensity treatments and away from Vyxeos that accelerated due to COVID-19 pandemic, we continue to see recovery in demand for Vyxeos and expect future demand for appropriate secondary AML patients to remain steady. In Europe, we continue to expect a negative impact on demand for and utilization of Vyxeos compared to historical periods due to COVID-19.
Defitelio provides an importantis the first and only approved treatment option for patients with VOD following HSCT. There was a significant decline in the number of patients receiving HSCT due to the effects of the COVID-19 pandemic. We anticipate the use of Defitelio will increase asto the extent that hospital systems globally are able to movecontinue moving forward with more HSCT procedures.
Erwinaze, which is approved to treat a limited population of patients with ALL who have developed hypersensitivity to E. coli-derived asparaginase, is licensed from and manufactured by a single source, Porton Biopharma Limited, or PBL. Our license and supply agreement with PBL expired on December 31, 2020. We expect to distribute Erwinaze through the first half of 2021. In the past, a significant challenge to maintaining sales of Erwinaze and a barrier to increasing sales was PBL’s inability to consistently supply product that meets specifications in quantities that are adequate to meet market demand. Given the urgent need for a reliable and high-quality recombinant asparaginase, we are focused on bringing JZP458 to market as quickly as possible. Our commercial team is currently preparing for its anticipated U.S. launch, targeted for mid-year 2021, subject to FDA approval.    
Research and Development Progress
Our development activities encompass all stages of development and currently include clinical testing of new product candidates and activities related to clinical improvements of, or additional indications or new clinical data for, our existing marketed products. We also have also expanded intoactive preclinical exploration ofprograms for novel therapies, including precision medicines in hematology and oncology.oncology and the GW cannabinoid platform. We are increasingly leveraging our growing internal research and development function, and we have also entered into collaborations with third parties for the research and development of innovative early-stage product candidates and have supported additional investigator-sponsored trials, or ISTs, that willare anticipated to generate additional data related to our products. We also seek out investment opportunities in support of development of early- and mid-stage technologies in our
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therapeutic areas and adjacencies. We have a number of licensing and collaboration agreements with third parties, including biotechnology companies, academic institutions and research-based companies and institutions, related to preclinical and clinical research and development activities in hematology and in precision oncology, as well as in neuroscience.
We remain on trackWith the approvals and launches of Rylaze for the treatment ALL or LBL in pediatric and adult patients one month and older who have developed hypersensitivity to E. coli-derived asparaginase and Xywav for IH in 2021, we accomplished our goal to deliver two important therapies to patients in 2021: Xywav in idiopathic hypersomnia, or IH,five product launches through 2020 and JZP458 in ALL.2021. We have taken both productsRylaze and Xywav from concept to commercial readiness, underscoringcommercialization.
Our neuroscience R&D efforts include the strengthplanned initiation of our portfolio and development capabilities.
At the American Academy of Neurology (AAN) Annual Meeting in April 2021, we presented positive results from thea pivotal Phase 3 clinical trial evaluating Xywavof Epidiolex for the treatment of Epilepsy with Myoclonic-Atonic Seizures, or EMAS, also known as Doose syndrome, in adultthe first half of 2022. This trial is expected to evaluate Epidiolex in a fourth childhood-onset epileptic encephalopathy with high unmet need. EMAS is characterized by generalized myoclonic-atonic seizures, and this trial is designed to provide the first randomized, controlled clinical data with Epidiolex in this syndrome type. Seizure types including atonic, tonic, clonic, tonic-clonic and partial onset seizures are seen in LGS, DS, and TSC.
For nabiximols, we have three ongoing Phase 3 clinical trials in MS-related spasticity. Spasticity occurs in up to 84% of MS patients, and approximately one-third of those who experience spasticity live with IH. IHuncontrolled symptoms. The first trial is a chronic neurological disorder thatsmaller, shorter trial relative to the other two. If results from this first trial are supportive, there is primarily characterized by EDS and that currently has no approved therapiesthe potential for a New Drug Application, or NDA, submission in the U.S. FDA granted Fast Track designation for Xywavby the end of 2022.
Additionally, in IH in September 2020, and we completed the rolling submission of a supplemental new drug application, or sNDA, in February 2021. Subsequently, FDA granted Priority Review and a PDUFA action date of August 12, 2021. We are planning for a potential commercial launch in the fourth quarter of 2021.
For JZP458,December 2021 we initiated a rolling biologics licensing application, or BLA, submission to FDA under Real-Time Oncology Review. We are working closely with FDA to complete the BLA submission and remain focused on bringing JZP458 to patients as quickly as possible. We are targeting a mid-2021 launch in the U.S., subject to FDA approval.
Additionally, we remain on track to begin planned Phase 2 clinical trials for JZP385 and JZP150 this yearsuvecaltamide (JZP385) for essential tremor, or ET, and for JZP150 for post-traumatic stress disorder, respectively.or PTSD. These are both patient populations whothat suffer significant impacts to their quality of life and for whom there are limited current treatment options. We are also pursuing early-stage activities related to the development of JZP324, an extended-release low sodium, oxybate formulation that we believe could provide a clinically meaningful option for narcolepsy patients.
Within our oncology R&D program, there is a robust development plan being executed for Zepzelca.We are collaborating with Roche on a pivotal Phase 3 clinical trial evaluating Zepzelca in combination with Tecentriq in first-line extensive stage SCLC. In December 2021, our licensor PharmaMar initiated a confirmatory trial in second-line SCLC. This is a three-arm trial comparing Zepzelca as either monotherapy or in combination with irinotecan to investigator's choice of irinotecan or topotecan. Data from this trial could confirm the benefit of Zepzelca in the treatment of SCLC when patients progress following first-line treatment with a platinum-based regimen.
In 2022 we initiated a Phase 2 basket trial to explore Zepzelca monotherapy in patients with select advanced or metastatic solid tumors. Cohorts will include advanced urothelial cancer, large cell neuroendocrine tumor of the lung, and homologous recombination deficient (HRD) cancers. In addition, we have initiated a Phase 4 observational study to collect real world safety and outcome data in adult Zepzelca monotherapy patients with SCLC who progress on or after prior platinum-containing chemotherapy.
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For Rylaze, in January 2022 we submitted an sBLA with data in support of a M/W/F IM dosing schedule and submitted a separate sBLA for intravenous administration in April 2022, both of which have been granted review under the RTOR program. We are planning regulatory submissions in Europe in mid-2022.
In the second quarter of 2022, we acquired development and commercialization rights to two preclinical compounds, consistent with our objective to expand our pipeline. In April 2022, we announced that we had entered into a licensing agreement with Werewolf Therapeutics, Inc., or Werewolf, to acquire exclusive global development and commercialization rights to Werewolf's investigational WTX-613, now referred to as JZP898. JZP898 is a differentiated, conditionally-activated interferon alpha (IFNα) INDUKINE™ molecule. Under the terms of the agreement, we made an upfront payment of $15 million to Werewolf, and Werewolf is eligible to receive development, regulatory and commercial milestone payments of up to $1.26 billion. Pending approval, Werewolf is eligible to receive a tiered, mid-single-digit percentage royalty on net sales of JZP898. This transaction underscores our commitment to enhancing our pipeline to deliver novel oncology therapies to patients, and also provides us with an opportunity to expand into immuno-oncology.
In May 2022, we announced that we had entered into a licensing agreement with Sumitomo Pharma Co., Ltd, or Sumitomo, to acquire exclusive development and commercialization rights in the United States, Europe and other territories for DSP-0187, which we have designated JZP441, a potent, highly selective oral orexin-2 receptor agonist with potential application for the treatment of narcolepsy, IH and other sleep disorders. Under the terms of the agreement, we will make an upfront payment of $50 million to Sumitomo, and Sumitomo is eligible to receive development, regulatory and commercial milestone payments of up to $1.09 billion. Pending approval, Sumitomo is eligible to receive a tiered, low double-digit royalty on Jazz's net sales of JZP441.
Below is a summary of our key ongoing and planned development projects related to our products and pipeline and their corresponding current stages of development:
Product CandidatesDescription
NEUROSCIENCE
Regulatory Review
XywavIH
Phase 3
ZepzelcaEpidiolexSmall cell lung cancerEMAS, also known as Doose syndrome (planned study)
NabiximolsMS Spasticity (multiple studies ongoing)
Spinal cord injury spasticity
(planned study)
Phase 2b
JZP385Suvecaltamide (JZP385)Essential tremor (plannedET (ongoing study)
Phase 2
JZP150Post-traumatic stress disorder (plannedPTSD (ongoing study)
Additional cannabinoidsAutism spectrum disorders (ongoing study)
Phase 1
JZP324Oxybate extended-release formulation (planned study)
Additional cannabinoidsNeonatal hypoxic-ischemic encephalopathy (ongoing study)
Neuropsychiatry targets (ongoing study)
Preclinical
JZP441 (DSP-0187)Potent, highly selective oral orexin-2 receptor agonist
Undisclosed targetsNeuroscience
Cannabinoids
ONCOLOGY
Regulatory Review
JZP458RylazeALL/lymphoblastic lymphoma, or LBL
FDA approval in June 2021; submitted sBLA in January 2022 seeking approval for Monday/Wednesday/Friday intramuscular dosing schedule; submitted separate sBLA seeking approval for intravenous administration; regulatory submission planned for Europe in mid-2022
Phase 3
ZepzelcaFirst-line extensive stage SCLC in combination with Tecentriq (collaboration with Roche) (ongoing study)
Confirmatory Study (PharmaMar study) (ongoing study)
VyxeosAML or high-risk Myelodysplastic Syndrome, or MDS (AML18 and AML19)(AML18) (cooperative group studies)

(ongoing study) Newly diagnosed adults with standard- and high-risk AML (AML Study Group cooperative group study)

(ongoing study) Newly diagnosed pediatric patients with AML (Children’s Oncology Group cooperative group study) (ongoing study)
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Product CandidatesDescription
Phase 2
ZepzelcaBasket trial including urothelial cancer, large cell neuroendocrine tumor of the lung, and HRD (homologous recombination deficient) cancers (ongoing study)
VyxeosHigh-risk MDS (European Myelodysplastic Syndromes Cooperative Group cooperative(cooperative group study) (ongoing study)

Newly diagnosed older adults with high-risk AML (cooperative group study) (planned cooperative group study)
Vyxeos + venetoclaxDe novo or relapsed/refractory, or R/R, AML (MD Anderson collaboration study) (ongoing study)
Phase 1
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Product CandidatesDescription
VyxeosLow intensity dosing for higher risk MDS (MD Anderson collaboration study) (ongoing study)
Vyxeos + other approved therapiesR/R AML or hypomethylating agent failure MDS (MD Anderson collaboration study) (ongoing study)

First-line, fit AML (Phase 1b study) (ongoing study)

Low intensity therapy for first-line, unfit AML (Phase 1b study) (ongoing study)
Preclinical
CombiPlex®
Hematology/oncology exploratory activities
JZP341 (long-acting Erwinia asparaginase)
ALL and other hematological malignancies (collaboration with Ligand Pharmaceuticals Incorporated, or Ligand)
JZP815/Pan-Raf inhibitor programRaf and Ras mutant tumors (acquired from Redx, Pharma, or Redx, which is continuing development)
JZP898Conditionally-activated interferon alpha (IFNα) INDUKINE™ molecule
Undisclosed targetsRas/Raf/MAP kinase pathway (collaboration with Redx)
Oncology
Exosome targets (NRAS and 3 others)(up to 4)Hematological malignancies/solid tumors (collaboration with Codiak BioSciences, Inc., or Codiak)
DefibrotideUndisclosed targetsExploratory activitiesOncology
Acquisition of GW Pharmaceuticals Plc Creates Innovative High-Growth, Global Biopharma Leader
In February 2021, we entered into an agreement to acquire GW Pharmaceuticals plc, or GW, with the objectives of broadening our neuroscience portfolio, further diversifying our revenue and driving sustainable, long-term value creation opportunities. Under the agreement, the total consideration to be paid by us for the entire issued share capital of GW is approximately $7.2 billion. The acquisition, which we refer to as the GW Acquisition, is expected to close in early May 2021.
GW specializes in discovering, developing, manufacturing and commercializing therapeutics from its proprietary cannabinoid product platform to address a broad range of diseases. GW's lead product, Epidiolex® (cannabidiol) oral solution, is approved in patients one-year and older for the treatment of seizures associated with Lennox-Gastaut Syndrome, Dravet Syndrome and Tuberous Sclerosis Complex, all of which are rare diseases characterized by severe early-onset epilepsy. Epidiolex was the first plant-derived cannabinoid medicine ever approved by FDA, and has also been approved in Europe under the trade name Epidyolex. In addition to the approved indications for Epidiolex, we believe there are considerable opportunities to pursue other indications within the epilepsy field, including other treatment-resistant epilepsies where significant unmet needs of patients exist.
GW is leveraging its scientific platform and specialized manufacturing expertise to develop additional cannabinoid-based therapies. This pipeline includes nabiximols, for which GW is in Phase 3 clinical trials for the treatment of spasticity associated with multiple sclerosis and spinal cord injury, as well as earlier-stage cannabinoid product candidates.
We view the transaction as consistent with our overall business and capital allocation strategy to expand our neuroscience portfolio and drive substantial value for our shareholders. We expect that product sales, operating expenses and interest expense will be significantly higher in 2021 than in 2020 due to the impact of the inclusion of the results of operations from GW commencing on closing the GW Acquisition, the higher debt balance in connection with the GW Acquisition and the continued growth of the organization.
Operational Excellence
We remain focused on continuing to build excellence in areas that we believe will give us a competitive advantage, including building an increasingly agile and adaptable commercialization engine and strengthening our customer-focused market expertise across patients, providers and payers.payors. We are refining our approach to engaging our customers by strengthening alignment and integration across functions and across regions.  This includes a more integrated approach to brand planning, a heightened focus on launch and operational excellence and multichannel customer engagement. We have fully adapted to virtual scientific congresses designed to ensure we can continue to provide promotional and non-promotional interactions and have supported our field-based teams with virtual customer interaction tools, training and content. These initiatives mark a significant operational evolution that is directly linked to our corporate strategy and are designed to better enable our teams to work collaboratively on an aligned and shared agenda through both virtual and in-person interactions.
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in-person interactions as medical congresses and healthcare practices begin to resume in-person activities, taking into account applicable public health authority and local government guidelines which are designed to ensure community and employee safety.
COVID-19 Business Update
We have implemented a comprehensive response strategy designed to effectively manage the impact of the COVID-19 pandemic on our employees, patients and our business. We have experienced limited financial and other impactsThe prolonged nature of the pandemic is negatively impacting our business in a varied manner due to the pandemic.emergence of the Delta and Omicron variants and other variants with increased transmissibility, even in some cases in vaccinated people, including limited access to health care provider offices and institutions and the willingness of patients or parents of patients to seek treatment or change existing treatments. We expect that our business, financial condition, results of operations and growth prospects may continue to be negatively impacted by the pandemic on a limited basis bythat may vary depending on the pandemic, albeitcontext. However we have begun to observe, and expect to continue to observe, a lesser extentgradual normalization in patient and health care provider practices, as providers and patients have adapted their behaviors and procedures to the evolving circumstances and as COVID-19 vaccines continue to be administered.
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Workplace and treatments reduce the global impact of COVID-19 and enable a resumption to more normal business practices and initiatives.Employees
We support broad public health strategies designed to prevent the spread of COVID-19 and are focused on the health and welfare of our employees. Our global organization has mobilized to enable our employees to accomplish our most critical goals through a combination of remote work and in-person initiatives. In addition to rolling out new technologies and collaboration tools, we have implemented processes and resources to support our employees in the event an employee receives a positive COVID-19 diagnosis. We have developed plans regarding the openingbegun reopening some of our sites to enable our employees to return to work in our global offices, the field and our manufacturing facilities, which take into account applicable public health authority and local government guidelines and which are designed to ensure community and employee safety. We plan to permanently moveare moving to a more flexible mix of virtual and in-person working to advance our culture, drive innovation and agility and enable greater balance and well-being for our workforce. This will also enable us to reconfigure our physical workspaces to optimize the footprint of our company-owned or leased office spaces.
Commercialization
While thereThere continues to be some negative impact on demand, new patient starts and treatments for our products arising from the pandemic, we have seen improvements asprimarily due to the inherent limitations of telemedicine and a reprioritization of healthcare resources toward COVID-19. As healthcare systems have adapted to cope with the ongoing situation.situation, we have seen improvements. We are utilizing technology to continue to engage healthcare professionals and other customers virtually to support patient care. As more clinics and institutions begin to allow in-person interactions pursuant to local health authority and government guidelines, our field teams continue to resume in-person interactions with healthcare professionals and clinics combined with virtual engagement. The level of renewed in-person engagement varies by account, region and country.country and may be adversely impacted in the future as a result of the continuing impact of the COVID-19 pandemic. The lack of access to healthcarehealth care providers has caused, and may continue to cause, delays in appropriate diagnosis, treatment and ongoing care for some patients, which has negatively impacted, and could subsequentlycontinue to impact, prescribing and use of our products.
Supply Chain
Our manufacturing facilities in Athlone, Ireland, which produces XyremXywav and Xywav, andXyrem, Villa Guardia, Italy, which produces defibrotide, and Kent Science Park, U.K., which produces Epidiolex/Epidyolex and Sativex, are operational with essential staff onsite and office-based staff working remotely.onsite and remotely as business needs require. We currently expect to have adequate global supply of Xyrem, Xywav, Sunosi, Zepzelca, Vyxeos, and Defitelio in 2021.all of our products for 2022.
Research and Development
With respect to our clinical trial activities, we have taken measures to implement remote and virtual approaches, including remote data monitoring where possible, to maintain patient safety and trial continuity and to preserve study integrity. We have seen limited COVID-19-related impact to our mid- and late-stage clinical trial activity, despite delays in initiating trial sites. We rely on contract research organizations or other third parties to assist us with clinical trials, and we cannot guarantee that they will continue to perform their contractual duties in a timely and satisfactory manner as a result of the evolving effects of the COVID-19 pandemic. Similarly, our ability to recruit and retain patients and principal investigators and site staff who, as healthcarehealth care providers, may have heightened exposure to COVID-19, may adversely impact our clinical trial operations.
Corporate Development and Other Financial Impacts
With our strong cash balance and positive cash flow, we anticipate having sufficient liquidity Supply chain disruptions related to continue to make planned investments in our business in support of our long-term growth strategy. However, the COVID-19 pandemic continues to rapidly evolve and has resulted in significant volatility in the global financial markets. If the disruption persists and deepens, we could experience an inability to access additional capital, which could in the future negatively affect our capacity for certain corporate development transactions or our ability to make other important, opportunistic investments. The effects of the pandemic couldmay also impact our ability to do in-person due diligence, negotiations, and other interactions to identify new opportunities.initiate clinical trials in a timely manner.
Corporate Response
The COVID-19 pandemic has caused a significant burden on health systems globally and has highlighted the need for companies to evaluate existing therapies to assess if they can be utilized beyond their current indications to treat COVID-19 as well as consider developing new therapies. To this end, we have granted requests for several ISTs to evaluate the use of defibrotide in COVID-19 patients experiencing respiratory distress.
In addition, we are supporting our local communities and patient-focused organizations in COVID-19 relief efforts including through corporate donations to charitable organizations providing food and medical relief to our communities in
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which we operate, in Italy, Philadelphia and the San Francisco Bay Area, and other localities where the needs related to the impact of COVID-19 are greatest. We are engaging with patient advocacy organizations to better understand the impact of COVID-19 and working to ensure thatenable patients living with sleep disorders, and hematologyepilepsies and oncology conditions continue to havewith access to treatments and that their other needs are addressed given the impact of COVID-19 on the healthcare system. We are committed to enabling our employees to give back, including allowing licensed healthcare practitioners employed by us to support local response efforts.
Other Challenges, Risks and Trends Related to Our Business
Our business has been substantially dependent on Xyrem. Our future plans assume that our newly launched oxybate product Xywav, with 92% lower sodium compared to Xyrem, depending on the dose, absence of a sodium warning and dosing titration option, will become the treatment of choice for patients who can benefit from oxybate treatment, including current Xyrem patients and patients who previously were not prescribed Xyrem including those patients for whom sodium content is a concern. In June 2021, FDA recognized seven years of
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ODE for Xywav in narcolepsy through July 21, 2027 stating that Xywav is clinically superior to Xyrem by means of greater safety due to reduced chronic sodium burden. While we expect that our business will continue to be substantially dependent on oxybate product sales from both XyremXywav and Xywav,Xyrem, there is no guarantee that we can maintain oxybate sales at or near historical levels, or that oxybate sales will continue to grow.
Our ability to successfully commercialize Xywav will depend on, among other things, our ability to obtain and maintain adequate coverage and reimbursement for Xywav and acceptance of Xywav by payers,payors, physicians and patients.patients, including of Xywav for the treatment of idiopathic hypersomnia in adults. In an effort to support strong adoption of Xywav, we are focused on providing robust patient accesscopay and savings programs and facilitating payerpayor coverage for Xywav. Moreover, we have increasingly experienced pressure from third party payerspayors to agree to discounts, rebates or restrictive pricing terms, for our products, and we cannot guarantee we will be able to agree to commercially reasonable terms with pharmacy benefit managers, or PBMs and other third party payers,payors, or that we will be able to ensure patient access to our existing and future products and acceptance of our products on institutional formularies. Entering into agreements with PBMs and payerspayors to ensure patient access has and will likely continue to result in higher gross to net deductions for these products.deductions. In addition to the COVID-19 related impacts described above, in the future, we expect our oxybate products to face competition from generic and authorized generic versions of sodium oxybate pursuant to the settlement agreements we have entered into with multiple abbreviated new drug application, or ANDA, filers. Generic competition can decrease the prices at which XyremXywav and XywavXyrem are sold and the number of prescriptions written for XyremXywav and Xywav.Xyrem. Xywav and Xyrem and Xywav may also face increased competition from new branded products for treatment of cataplexy and/or EDS in narcolepsy in the U.S. market.
As for other products in our neuroscience therapeutic area, if we are unable to successfully commercialize Sunosi in the U.S. and Europe, or if sales of Sunosi do not reach the levels we expect, our anticipated revenue from Sunosi will be negatively affected, which would have a material adverse effect on our business,Our financial condition, results of operations and growth prospects.prospects are also dependent on our ability to maintain or increase sales of Epidiolex/Epidyolex in the U.S. and Europe, which is subject to many risks and there is no guarantee that we will be able to continue to successfully commercialize Epidiolex for its approved indications. The commercial success of Epidiolex depends on the extent to which patients and physicians accept and adopt Epidiolex as a treatment for seizures associated with LGS, DS and TSC, and we do not know whether our or others’ estimates in this regard will be accurate. Physicians may not prescribe Epidiolex and patients may be unwilling to use Epidiolex if coverage is not provided or reimbursement is inadequate to cover a significant portion of the cost. Additionally, any negative development for Epidiolex in the market after launch, in clinical development for additional indications, or in regulatory processes in other jurisdictions, may adversely impact the commercial results and potential of Epidiolex. Thus, significant uncertainty remains regarding the commercial potential of Epidiolex.
In addition to our neuroscience products and product candidates, we are commercializing a portfolio of oncology products, including Defitelio, Erwinaze, Vyxeos, Rylaze and Zepzelca. An inability to effectively commercialize Defitelio, Vyxeos, Rylaze and Zepzelca and to maximize their potential where possible through successful research and development activities could have a material adverse effect on our business, financial condition, results of operations and growth prospects.
Our license and supply agreement with PBL, a limited liability company wholly owned by the UK Secretary of State for Health which includes an exclusive right to market, sell or distribute Erwinaze, an exclusive license to Erwinaze trademarks, and a non-exclusive license to PBL’s manufacturing know-how, expired on December 31, 2020. Under our agreement with PBL, we have the right to sell certain Erwinaze inventory for a post-termination sales period of 12 months and retain ownership of certain data, know-how and other property interests, including the BLA for Erwinaze in the U.S. and marketing authorizations for Erwinase in several other countries. We expect to distribute available Erwinaze supply during the first half of 2021. In addition, if we are unable to replace the future product sales we will lose from Erwinaze with our existing or future products, our business, financial condition, results of operations and growth prospects would be materially adversely affected.
A key aspect of our growth strategy is our continued investment in our evolving and expanding research and development activities. If we are not successful in the clinical development of these or other product candidates, if we are unable to obtain regulatory approval for our product candidates in a timely manner, or at all, or if sales of an approved product do not reach the levels we expect, our anticipated revenue from our product candidates would be negatively affected, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.
In addition to continued investment in our research and developmentR&D pipeline, we intend to continue to grow our business by acquiring or in-licensing, and developing, including with collaboration partners, additional products and product candidates that we believe are highly differentiated and have significant commercial potential. Failure to identify and acquire, in-license or develop additional products or product candidates, successfully manage the risks associated with integrating any products or product candidates into our portfolio or the risks arising from anticipated and unanticipated problems in connection with an acquisition or in-licensing, such as the pending GW Acquisition, could have a material adverse effect on our business, results of
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operations and financial condition. In particular, the
The success of the GW Acquisition will depend, in part, on our ability to realize the anticipated benefits from successfully combining our and GW’s businesses and we plan to continue to devote substantial management attention and resources to integrating our business practices and operations with GW’s so that we canin an effort to fully realize the anticipated benefits of the pending acquisition.GW Acquisition. Nonetheless, Epidiolex and the other products and technologies acquired may not be successful or continue to grow at the same rate as whenif our companies operated independently or they may require significantly greater resources and investments than originally anticipated. The acquisition could also resultConversely, the liabilities assumed in the assumption of unknown or contingent liabilities.GW Acquisition may be greater than originally anticipated. In addition, difficulties may arise during the process of combining the operations of our companies that could result in the failure to achieve the synergies or free cash flow that we anticipate, the failure to integrate operations and internal systems, programs and controls, the loss of key employees that may be difficult to replace in the very competitive pharmaceutical field, the failure to harmonize both companies’ corporate cultures, and the disruption of each company’s ongoing businesses or inconsistencies in standards, controls, procedures and policies that adversely affect our ability to maintain relationships with customers, suppliers, distributors, collaboration partners, clinical trial investigators or managers of our clinical trials. As a result, the anticipated benefits of the pending acquisitionGW Acquisition may not be realized fully within the expected
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timeframe or at all or may take longer to realize or cost more than expected, which could materially and adversely affect our business, financial condition, results of operations and growth prospects.
Our industry has been, and is expected to continue to be, subject to healthcare cost containment and drug pricing scrutiny by regulatory agencies in the U.S. and internationally. If healthcare policies or reforms intended to curb healthcare costs are adopted or if we experience negative publicity with respect to pricing of our products or the pricing of pharmaceutical drugs generally, the prices that we charge for our products may be affected, our commercial opportunity may be limited and/or our revenues from sales of our products may be negatively impacted. We are also subject to increasing pricing pressure and restrictions on reimbursement imposed by payers.payors. If we fail to obtain and maintain adequate formulary positions and institutional access for newly-launchedour products such as Sunosi, Xywav, Zepzelca and future approved products, we will not be able to achieve a return on our investment and our business, financial condition, results of operations and growth prospects would be materially adversely affected.
While certain preparations of cannabis remain Schedule I controlled substances, if such products are approved by FDA for medical use in the U.S. they are rescheduled to Schedules II-V, since approval by FDA satisfies the “accepted medical use” requirement; or may be removed from control under the Controlled Substances Act entirely. If any of our product candidates receive FDA approval, the U.S. Drug Enforcement Administration, or DEA, will make a scheduling determination. If any foreign regulatory authority determines that Epidyolex may have potential for abuse, or if DEA makes a similar determination for nabiximols, it may require us to generate more clinical or other data than we currently anticipate to establish whether or to what extent the substance has an abuse potential, which could increase the cost, delay the approval and/or delay the launch of that product. In addition, there are non-FDA approved cannabidiol preparations being made available from companies through the state-enabled medical marijuana industry, which might attempt to compete with Epidiolex and, if approved by FDA, nabiximols. If we are unable to compete successfully, our commercial opportunities will be reduced and our business, results of operations and financial conditions may be materially harmed.
Finally, business practices by pharmaceutical companies, including product formulation improvements, patent litigation settlements, and risk evaluation and mitigation strategy, or REMS, programs, have increasingly drawn public scrutiny from legislators and regulatory agencies, with allegations that such programs are used as a means of improperly blocking or delaying competition. If we become the subject of any future government investigation with respect to our business practices, including as they relate to the Xywav and Xyrem REMS, the launch of Xywav, our Xyrem patent litigation settlement agreements or otherwise, we could incur significant expense and could be distracted from operation of our business and execution of our strategy. From June 2020 to September 2020,February 2022, a number of class action lawsuits were filed on behalf of purported direct and indirect Xyrem purchasers, alleging that the patent litigation settlement agreements we entered with certain generic companies violate state and federal antitrust and consumer protection laws. For additional information on these class action complaints,lawsuits, see Note 11,9, Commitments and Contingencies-Legal Proceedings of the Notes to Condensed Consolidated Financial Statements, included in Part I Item 1 of this Quarterly Report on Form10-Q.  10‑Q. It is possible that additional lawsuits will be filed against us making similar or related allegations. We cannot predict the outcome of these or potential additional lawsuits or government action; however, if the plaintiffs were to be successful in their claims, they may be entitled to injunctive relief or we may be required to pay significant monetary damages. Any of the foregoing risks and uncertainties could have a material adverse effect on our business, financial condition, results of operations and growth prospects. In addition, to the extent the COVID-19 pandemic continues to adversely affect our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties described above. All of these risks and uncertainties are discussed in greater detail, along with other risks and uncertainties, in “Risk Factors” in in Part I, Item 1A of the annual report on Form 10-K for the year ended December 31, 20202021., filed with the Securities and Exchange Commission on February 23, 2021, or the 2020 Form 10-K.

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Results of Operations
The following table presents our revenues and expenses (in thousands, except percentages): 
Three Months Ended
March 31,
Increase/ Three Months Ended
March 31,
Increase/
20212020(Decrease) 2022
2021(1)
(Decrease)
Product sales, netProduct sales, net$603,531 $530,205 14 %Product sales, net$809,837 $603,531 34 %
Royalties and contract revenuesRoyalties and contract revenues4,050 4,521 (10)%Royalties and contract revenues3,884 4,050 (4)%
Cost of product sales (excluding amortization of acquired developed technologies)Cost of product sales (excluding amortization of acquired developed technologies)40,189 28,657 40 %Cost of product sales (excluding amortization of acquired developed technologies)115,284 40,189 N/A(2)
Selling, general and administrativeSelling, general and administrative260,508 208,400 25 %Selling, general and administrative308,813 260,508 19 %
Research and developmentResearch and development76,573 86,107 (11)%Research and development129,981 76,573 70 %
Intangible asset amortizationIntangible asset amortization68,192 62,847 %Intangible asset amortization172,094 68,192 N/A(2)
Impairment charge— 136,139 N/A(1)
Acquired in-process research and development— 202,250 N/A(1)
Interest expense, netInterest expense, net27,376 18,496 48 %Interest expense, net70,684 27,376 N/A(2)
Foreign exchange (gain) loss(943)1,132 (183)%
Foreign exchange loss (gain)Foreign exchange loss (gain)10,540 (943)N/A(2)
Income tax provision (benefit)18,019 (51,287)(135)%
Equity in gain of investees(4,165)(182)2,188 %
Income tax expenseIncome tax expense536 18,019 N/A(2)
Equity in loss (gain) of investeesEquity in loss (gain) of investees4,142 (4,165)N/A(2)
_________________________________________________________
(1)The results of operations of the GW business have been included from the closing of the acquisition of GW on May 5, 2021.
(2)Comparison to prior period not meaningful.
Revenues
The following table presents our net product sales, royalties and contract revenues, and total revenues (in thousands, except percentages):
Three Months Ended
March 31,
Increase/ Three Months Ended
March 31,
Increase/
20212020(Decrease) 2022
2021(1)
(Decrease)
XyremXyrem$335,550 $407,875 (18)%Xyrem$247,497 $335,550 (26)%
XywavXywav75,416 — N/A(1)Xywav186,080 75,416 147 %
Total OxybateTotal Oxybate410,966 407,875 % Total Oxybate433,577 410,966 %
Epidiolex/EpidyolexEpidiolex/Epidyolex157,893 — N/A(2)
SunosiSunosi11,606 1,924 503 %Sunosi15,878 11,606 37 %
SativexSativex4,742 — N/A(2)
Total NeuroscienceTotal Neuroscience422,572 409,799 %Total Neuroscience612,090 422,572 45 %
ZepzelcaZepzelca54,334 — N/A(1)Zepzelca59,338 54,334 %
RylazeRylaze54,220 — N/A(2)
VyxeosVyxeos33,155 32,720 %Vyxeos33,757 33,155 %
Defitelio/defibrotideDefitelio/defibrotide49,619 47,432 %Defitelio/defibrotide49,489 49,619 — %
Erwinaze/ErwinaseErwinaze/Erwinase41,068 37,732 %Erwinaze/Erwinase— 41,068 N/A(2)
Total OncologyTotal Oncology178,176 117,884 51 %Total Oncology196,804 178,176 10 %
OtherOther2,783 2,522 10 %Other943 2,783 (66)%
Product sales, netProduct sales, net603,531 530,205 14 %Product sales, net809,837 603,531 34 %
Royalties and contract revenuesRoyalties and contract revenues4,050 4,521 (10)%Royalties and contract revenues3,884 4,050 (4)%
Total revenuesTotal revenues$607,581 $534,726 14 %Total revenues$813,721 $607,581 34 %
_____________________________
(1)The results of operations of the GW business have been included from the closing of the acquisition of GW on May 5, 2021.
(2)Comparison to prior period not meaningful.

Product Sales, Net
Total oxybate product sales increased by $22.6 million in the three months ended March 31, 20212022 compared to the same period in 2020 primarily due to a higher average selling price, partially offset by a decrease in commercial sales volumes2021. . Total oxybate revenue bottle volume decreasedincreased by 3% in the three months ended March 31, 20212022 compared to
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the same period in 20202021 reflecting our continued investment in patient access programs during the launch of Xywav. Average active oxybate patients on therapy were approximately 15,70016,650 in the first quarter of 2021,2022, an increase of approximately 4%approximately 6% compared to the same period in 2020.2021. Xyrem product sales decreased in the three months ended March 31, 20212022 compared to the same period in 20202021 primarily due
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to a decrease in sales volume, reflecting the continued adoption of Xywav by existing Xyrem patients, and to a lesser extent higher gross to net deductions, partially offset by a higher average net selling price. Price increases were instituted in January 20202021 and January 2021. Xyrem product sales volume decreased in the three months ended March 31, 2021, compared to the same period in 2020 driven by the strong adoption of2022. Xywav by existing Xyrem patients. Xywav product sales in the three months ended March 31, 2021 were $75.4 million, following its U.S. launch in November 2020. Sunosi product sales increased in the three months ended March 31, 2021,2022 compared to the same period in 20202021 primarily due to an increase inhigher sales volume.Sunosi launched in the U.S. in July 2019 and the European rolling launch commenced in May 2020.
Zepzelcavolumes, with bottle volume increasing by 148%. Epidiolex/Epidyolex product sales were $54.3 million in the three months ended March 31, 2021 following its U.S. launch in July 2020. Vyxeos2022 were $157.9 million. On a pro forma basis, Epidiolex/Epidyolex product sales forincreased by 6% in the three months ended March 31, 2021 were in line with2022 compared to the same period in 2020. Defitelio/defibrotide2021, primarily due to an increase in commercial sales volumes and higher average net selling price. Price increases were instituted in January 2021 and January 2022. Sunosi product sales increased in the three months ended March 31, 20212022, compared to the same period in 20202021 primarily due to the positive impact of foreign exchange rates. Erwinaze/Erwinasean increase in sales volume.
Zepzelca product sales increased in the three months ended March 31, 20212022 compared to the same period in 20202021 primarily due to a higher average net selling price. Price increases were instituted in July 2021 and January 2022. Rylaze product sales were $54.2 million in the timing of availability of supply of inventory from the manufacturer.
Royaltiesthree months ended March 31, 2022, following its U.S. launch in July2021. Vyxeos and Contract Revenues
Royalties and contract revenues decreased inDefitelio/defibrotide product sales for the three months ended March 31, 2021 compared to2022 were in line with the same period in 20202021. We distributed our final Erwinaze inventory in June 2021 following expiration of our license and supply agreement.
We expect total product sales, net will increase in 2022 over 2021, primarily due to lower revenues from out-licensing agreements.an increase in sales of Xywav partially offset by a decrease in Xyrem as patients continue to transition to Xywav, expected growth in, and the inclusion of a full year sales of, Epidiolex and Rylaze and expected growth in Zepzelca, partially offset by an expected reduction in Sunosi upon completion of the sale to Axsome.
Cost of Product Sales
Cost of product sales increased in the three months ended March 31, 20212022 compared to the same period in 20202021 primarily due to changesthe cost of product sales acquired in product mix.the acquisition of GW, including the acquisition accounting inventory fair value step-up expense, or fair value step-up expense of $63.9 million. Gross margin as a percentage of net product sales was 93.3%85.8% for the three months ended March 31, 20212022 compared to 94.6%93.3% for the same period in 2020.2021. The decrease in our gross margin percentage was primarily due to the impact of the fair value step-up expense. We expect our cost of product sales to increase in 2022 compared to 2021 primarily driven by the inclusion of a full year of fair value step-up expense.
Selling, General and Administrative Expenses
Selling, general and administrative expenses increased in the three months ended March 31, 20212022 compared to the same period in 20202021, primarily due to increased investmentan increase in sales, marketingcompensation-related expenses driven by higher headcount due to the acquisition of GW. We expect selling, general and launch activitiesadministrative expenses in 2022 to decrease compared to 2021, primarily due to a reduction in transaction and integration-related expenses and a reduction in costs associated with Sunosi upon completion of the sale to Axsome, together with synergies expected to be realized in connection with the commencementacquisition of GW, partially offset by the Sunosi direct-to-consumer marketing campaign in the U.S. and the continuationinclusion of the launchesa full year of Zepzelca and Xywav in the U.S., transaction expensesexpense related to the proposedacquired GW Acquisition as well as an increase in other expenses related to the expansion of our business.
Research and Development Expenses
Research and development expenses consist primarily of costs related to clinical studies and outside services, personnel expenses, and other research and development costs. Clinical study and outside services costs relate primarily to services performed by clinical research organizations, materials and supplies, and other third party fees. Personnel expenses relate primarily to salaries, benefits and share-based compensation. Other research and development expenses primarily include overhead allocations consisting of various support and facilities-related costs. We do not track fully-burdened research and development expenses on a project-by-project basis. We manage our research and development expenses by identifying the research and development activities that we anticipate will be performed during a given period and then prioritizing efforts based on our assessment of which development activities are important to our business and have a reasonable probability of success, and by dynamically allocating resources accordingly. We also continually review our development pipeline projects and the status of their development and, as necessary, reallocate resources among our development pipeline projects that we believe will best support the future growth of our business.
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The following table provides a breakout of our research and development expenses by major categories of expense (in thousands):
Three Months Ended
March 31,
Three Months Ended
March 31,
2021202020222021
Clinical studies and outside servicesClinical studies and outside services$31,046 $47,749 Clinical studies and outside services$56,429 $31,046 
Personnel expensesPersonnel expenses36,226 25,902 Personnel expenses55,301 36,226 
OtherOther9,301 12,456 Other18,251 9,301 
TotalTotal$76,573 $86,107 Total$129,981 $76,573 
Research and development expenses decreasedincreased by $9.5$53.4 million in the three months ended March 31, 2021,2022, compared to the same period in 2020.2021. Clinical studies and outside services costs decreased by $16.7 millionincreased in the three months ended
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March 31, 2021,2022 compared to the same period in 20202021 primarily due to a decrease in expensesthe addition of costs related to our clinical programs including JZP458.for Epidiolex, nabiximols, cannabinoids and an increase in costs related to JZP150 and suvecaltamide (JZP385). Personnel expenses increased by $10.3$19.1 million in the three months ended March 31, 2021,2022, compared to the same period in 2020 primarily2021 due to increased headcount in supportprimarily driven by the acquisition of GW.
For 2022, we expect that our research and development programs.expenses will continue to increase from previous levels due to the inclusion of a full year of expense with respect to the acquired GW business and as we prepare for anticipated data read-outs from clinical trials, initiate and undertake additional clinical trials and related development work and potentially acquire rights to additional product candidates.
Intangible Asset Amortization
Intangible asset amortization increased by $5.3$103.9 million in the three months ended March 31, 20212022, compared to the same period in 20202021 primarily due to the impactinclusion of changes in foreign exchange rates on euro-denominated intangible assets and the commencement of amortization of the Zepzelca intangible asset upon FDA approval in June 2020.
Impairment Charge
Inassets arising from the three months ended March 31, 2020, we recorded an acquired in-process research and development, or IPR&D, asset impairment chargeacquisition of $136.1 million following the decision to stop enrollment in our Phase 3 clinical study of defibrotide for the prevention of VOD due to a determination that the study is highly unlikely to reach one of its primary endpoints.
Acquired In-Process Research and Development
Acquired IPR&D expense in the three months ended March 31, 2020GW, primarily related to an upfront paymentEpidiolex. Intangible asset amortization is expected to increase in 2022 compared to 2021 primarily as a result of $200.0 million to PharmaMarthe inclusion of a full years amortization on the intangible assets acquired in connection with our license agreement.the acquisition of GW.
Interest Expense, Net
Interest expense, net increased by $8.9$43.3 million in the three months ended March 31, 20212022, compared to the same period in 2020,2021, primarily due to higher non-cash interest expense followingfrom (i) a seven-year $3.1 billion term loan B facility, or the issuance of our 2.00% exchangeableDollar Term Loan and (ii) a seven-year $625.0 million term loan B facility, or the Euro Term Loan, together with the Dollar Term Loan, collectively known as the Term Loan and 4.375% senior secured notes, due 2026,2029, or the 2026 Notes,Secured Notes. We expect interest expense, net for 2022 to be broadly in June 2020 and lower interest income.line with 2021.
Foreign Exchange Loss (Gain) Loss
The foreign exchange loss (gain) loss is primarily related to the translation of sterling and euro-denominated net monetary liabilities, primarily intercompany balances, held by subsidiaries with a U.S. dollar functional currency and related foreign exchange forward contracts not designated as hedging instruments.
Income Tax Provision (Benefit)Expense
Our income tax provisionexpense was $18.0$0.5 million in the three months ended March 31, 2021, compared to an income tax benefit of $51.3 million for the same period in 2020. The effective tax rate was 13.3% in the three months ended March 31, 2021 compared to 24.5% for the same period in 2020. The decrease in the effective tax rate for the three months ended March 31, 20212022, compared to $18.0 million for the same period in 2020 was2021. The decrease in the income tax expense resulted primarily due tofrom the impactmix of the defibrotide acquired IPR&D asset impairment chargepre-tax income and the acquired IPR&D expense relating to the $200.0 million upfront payment to PharmaMar for the exclusive U.S. commercialization and development rights to Zepzelca in 2020, and changes in income mix among the various jurisdictions in which we operate. The effectivelosses incurred across tax rate for the three months ended March 31, 2021 was higher than the Irish statutory rate of 12.5% primarily due to the impact of various expenses not deductible for tax purposes, income taxable at a rate higher than the Irish statutory rate and uncertain tax positions, partially offset by deductions available in respect of subsidiary equity and originating tax credits.jurisdictions. We do not provide for Irish income taxes on undistributed earnings of our foreign operations that are intended to be indefinitely reinvested in our foreign subsidiaries.
Equity in Earnings of Investees
Equity in earnings of investees relates to our share in the net gain of companies in which we have made investments accounted for under the equity method of accounting.

Liquidity and Capital Resources
As of March 31, 2021,2022, we had cash and cash equivalents and investments of $2.4 billion,$490.8 million, borrowing availability under our revolving credit facility of $1.6 billion$500.0 million and long-term debt principal balance of $2.4$6.2 billion. Our long-term debt included $575.9 million$3.1 billion in aggregate principal amount term loan, $218.8 millionof the Dollar Term Loan, $1.5 billion in aggregate principal amount of our 1.875%the Secured Notes, $1.0 billion principal amount of the 2.00% exchangeable senior notes due 2021,2026, or the 20212026 Notes and $575.0 million principal amount of ourthe 1.50% exchangeable senior notes due 2024, or the 2024 Notes, and $1.0 billion principal amount of our 2026 Notes. We generated cash flows from operations of $285.0$209.0 million during the three months ended March 31, 2021,2022, and we expect to continue to generate positive cash flows from operations during 2021.which will enable us to operate our business and de-lever our balance sheet over time.
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On April 20, 2021,In the first quarter of 2022, we and certain of our wholly-owned subsidiaries, entered into Amendment No. 3 to our Credit Agreement, dated as of June 18, 2015,repaid €208.3 million, or $251.0 million which represents the Existing Credit Agreement, with the lenders party thereto and Bank of America, N.A., as administrative agent, collateral agent, letter of credit issuer and swing line lender. The Amendment No. 3 amended the Existing Credit Agreement to permit the issuance of senior secured notes and made certain related changes as set forth therein.
On April 29, 2021, our wholly-owned subsidiary, Jazz Securities Designated Activity Company, issued $1.5 billion in aggregateremaining principal amount of 4.375% senior secured notes due 2029.
Concurrently withthe Euro Term Loan. We have made voluntary repayments of €625.0 million, or $753.0 million, relating to Euro Term Loan and mandatory repayments of $23.3 million relating to the Dollar Term Loan since the closing of the acquisition of GW Acquisition, we expect to enter into new senior secured credit facilities, which is expected to consist ofin  May 2021.
We have a $500.0 million revolving credit facility and a term loan B facility in an aggregatesignificant amount of approximately $3.85 billion. We expectdebt outstanding on a consolidated basis. For a more detailed description of our debt arrangements, including information relating to use term loan B borrowings under new senior secured credit facilities and the net proceeds from the senior secured notes, togetherour scheduled maturities with cash on handrespect to fund the cash consideration payable in connection with the GW Acquisition. The senior secured notes have a mandatory redemption clause that will be triggered under certain circumstances, including failure to complete the acquisition within the time period outlined in the GW Transaction Agreement or the terminationour long-term debt, see Note 8, Debt, of the GW Acquisition.notes to the condensed consolidated financial statements, included in Part I, Item 1 of this Quarterly Report on Form 10‑Q. This substantial level of debt could have important consequences to our business, including, but not limited to the factors set forth in “Risk Factors” in Part I, Item 1A in our Annual Report on Form 10-K for the year ended December 31, 2021 under the heading "We have incurred substantial debt, which could impair our flexibility and access to capital and adversely affect our financial position, and our business would be adversely affected if we are unable to service our debt obligations.”
We believe that our existing cash and cash equivalents, and investments balances, cash we expect to generate from operations and funds available under our revolving credit facilityRevolving Credit Facility will be sufficient to fund our operations and to meet our existing obligations for the foreseeable future. The adequacy of our cash resources depends on many assumptions, including primarily our assumptions with respect to product sales and expenses, as well as the other factors set forth in “Risk Factors” in Part I, Item 1A in our Annual Report on Form 10-K for the year ended December 31, 20202021 under the headings “Risks Related to our Lead Products and Product Candidates” and “To continue to grow our business, we will need to commit substantial resources, which could result in future losses or otherwise limit our opportunities or affect our ability to operate and grow our business.” Our assumptions may prove to be wrong or other factors may adversely affect our business, and as a result we could exhaust or significantly decrease our available cash resources, and we may not be able to generate sufficient cash to service our debt obligations which could, among other things, force us to raise additional funds and/or force us to reduce our expenses, either of which could have a material adverse effect on our business.
To continue to grow our business over the longer term, we plan to commit substantial resources to product acquisition and in-licensing, product development, clinical trials of product candidates and expansion of our commercial, development, manufacturing and other operations. In this regard, we have evaluated and expect to continue to evaluate a wide array of strategic transactions as part of our strategy to acquire or in-license and develop additional products and product candidates. Acquisition opportunities that we pursue could materially affect our liquidity and capital resources and may require us to incur additional indebtedness, seek equity capital or both. We regularly evaluate the performance of our products and product candidates to ensure fit within our portfolio and support efficient allocation of capital. In addition, we may pursue new operations or continue the expansion of our existing operations. Accordingly, we expect to continue to opportunistically seek access to additional capital to license or acquire additional products, product candidates or companies to expand our operations or for general corporate purposes. Raising additionaladditional capital could be accomplished through one or more public or private debt or equity financings, collaborations or partnering arrangements. However, as a result of the COVID-19 pandemic continues to rapidly evolve and has resulted in significant volatility in the global financial markets. markets have experienced significant volatility. If the disruptionthis volatility persists and deepens, we could experience an inability to access additional capital or an impact onour liquidity could otherwise be impacted, which could in the future negatively affect our capacity for certain corporate development transactions or our ability to make other important, opportunistic investments. In addition, as a matter of Irish law, when an Irish public limited company issues ordinary shares to new shareholders for cash, the company must first offer those shares on the same or more favorable terms to existing shareholders on a pro rata basis, unless this statutory pre-emption obligation is dis-applied, or opted-out of, by approval of its shareholders. At our extraordinary general meeting of shareholders in September 2021, our shareholders voted to approve our proposal to dis-apply the statutory pre-emption obligation on terms that are substantially more limited than our general preemption opt-out authority that had been in effect prior to August 4, 2021, which could adversely affect our ability to effectively use our unissued share capital to fund in-licensing or acquisition opportunities, or to otherwise raise additional capital for our business. In any event, an inability to borrow or raise additional capital in a timely manner and on attractive terms could prevent us from expanding our business or taking advantage of acquisition opportunities, and could otherwise have a material adverse effect on our business and growth prospects. In addition, if we use a substantial amount of our funds to acquire or in-license products or product candidates, we may not have sufficient additional funds to conduct all of our operations in the manner we would otherwise choose. Furthermore, any equity financing would be dilutive to our shareholders, and could require the consent of the lenders under the amended credit agreement could be requiredCredit Agreement and the indenture for the Secured Notes for certain financings.
In November 2016, our board of directors authorized a share repurchase program and as of March 31, 2021 had authorized the repurchase of ordinary shares having an aggregate purchase price of up to $1.5 billion, exclusive of any brokerage commissions. Under this program, which has no expiration date, we may repurchase ordinary shares from time to time on the open market.  The timing and amount of repurchases will depend on a variety of factors, including the price of our ordinary shares, alternative investment opportunities, restrictions under the amended credit agreement, corporate and regulatory requirements and market conditions. The share repurchase program may be modified, suspended or discontinued at any time without prior notice. During the three months ended March 31, 2021, we did not repurchase any of our ordinary shares. As of March 31, 2021, the remaining amount authorized under the share repurchase program was $431.2 million.
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The following table presents a summary of our cash flows for the periods indicated (in thousands):
 Three Months Ended
March 31,
 20212020
Net cash provided by operating activities$284,997 $272,969 
Net cash provided by (used in) investing activities737,132 (60,080)
Net cash provided by (used in) financing activities18,276 (147,683)
Effect of exchange rates on cash and cash equivalents(641)(948)
Net increase in cash and cash equivalents$1,039,764 $64,258 
 Three Months Ended
March 31,
 20222021
Net cash provided by operating activities$208,979 $284,997 
Net cash (used in) provided by investing activities(37,292)737,132 
Net cash (used in) provided by financing activities(270,811)18,276 
Effect of exchange rates on cash and cash equivalents(1,489)(641)
Net (decrease) increase in cash and cash equivalents$(100,613)$1,039,764 
Operating activities
Net cash provided by operating activities increaseddecreased by $12.0$76.0 million in the three months ended March 31, 20212022 compared to the same period in 2020,2021, primarily due to:
An increaseto a decrease in net cash inflow related to changes in operating assets and liabilities primarily driven by the timing of payments to suppliers, partially offset by the timing of receipts from customers.liabilities.
Investing activities
Net cash (used in) provided by (used in) investing activities increaseddecreased by $797.2$774.4 million in the three months ended March 31, 20212022 compared to the same period in 2020,2021, primarily due to the following:
$579.3739.3 million increase in net proceeds from maturity of investments, primarily time deposits;
$202.3 million decrease in upfront payments for acquired IPR&D primarily driven by the $200.0 million payment under our license agreement with PharmaMardeposits, in the three months ended March 31, 2020.2021; and
$25.0 million milestone payment to PharmaMar in relation to our first sales-based milestone for Zepzelca in the three months ended March 31, 2022.
Financing activities
Net cash (used in) provided by (used in) financing activities increaseddecreased by $166.0$289.1 million in the three months ended March 31, 20212022 compared to the same period in 2020,2021, primarily due to:
The impactRepayment of share repurchaseslong-term debt of $139.1$258.8 million in the three months ended March 31, 2020;2022, compared to $8.3 million in the three months ended March 31, 2021;
An increaseA decrease of $37.1$28.7 million in proceeds from employee equity incentive and purchase plans; partially offset byand
An increase of $10.2$10.0 million in payment of employee withholding taxes related to share-based awards.

Debt
The summary of our outstanding indebtedness under our financing arrangements is included in Note 9,8, Debt, of the Notes to Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10-Q. During the three months ended March 31, 2021,2022, there were no material changes to the amended credit agreement, as set forth in Note 11,12, Debt, of the Notes to Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 2020.
On April 29, 2021, our wholly-owned subsidiary, Jazz Securities Designated Activity Company, issued $1.5 billion in aggregate principal amount of 4.375% senior secured notes due 2029.2021.

Contractual Obligations
During the three months ended March 31, 2021,2022, there were no material changes to our contractual obligations as set forth in Part II, Item 7 “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the year ended December 31, 2020.2021.

Critical Accounting Estimates
To understand our financial statements, it is important to understand our critical accounting estimates. The preparation of our financial statements in conformity with U.S. generally accepted accounting principles requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the
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date of the financial statements and the reported amounts of revenues and expenses during the reporting period. Significant estimates and assumptions are required in determining the amounts to be deducted from gross revenues in particular estimatesand also with respect to the acquisition and valuation of government rebates, which include Medicaid and TRICARE rebates, commercial contracting and estimated product returns. Significant estimates and assumptions are also required to determine whether to capitalize intangible assets, the amortization periods for identifiable intangible assets, the potential impairment of goodwill and other intangible assetsintangibles and income taxes. Some of these judgments can be subjective and complex, and,
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consequently, actual results may differ from these estimates. For any given individual estimate or assumption we make, there may also be other estimates or assumptions that are reasonable. Although we believe our estimates and assumptions are reasonable, they are based upon information available at the time the estimates and assumptions were made.
Our critical accounting policies and significant estimates are detailed in our Annual Report on Form 10-K10‑K for the year ended December 31, 2020.2021. Our critical accounting policies and significant estimates have not changed substantially from those previously disclosed in our Annual Report on Form 10-K10‑K for the year ended December 31, 2020.

Off-Balance Sheet Arrangements
We do not have any off-balance sheet arrangements.2021.

Cautionary Note Regarding Forward-Looking Statements
This Quarterly Report on Form 10-Q10‑Q contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. Forward-looking statements are based on our management’s current plans, objectives, estimates, expectations and intentions and on information currently available to our management. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “could,” “would,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “predict,” “propose,” “intend,” “continue,” “potential,” “possible,” “foreseeable,” “likely,” “unforeseen” and similar expressions intended to identify forward-looking statements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance, time frames or achievements to be materially different from any future results, performance, time frames or achievements expressed or implied by the forward-looking statements. These known and unknownWe discuss many of these risks, uncertainties and other risk factors include, without limitation:
We may not realize the anticipated benefits and synergies from our pending GW Acquisition.
The GW Acquisition may not be completed on the currently contemplated timeline or terms, or at all.
Failure to complete the GW Acquisition could have a material and adverse effect on us.
The indebtedness of the combined company following the consummation of the GW Acquisition will be substantiallyin greater than our indebtedness on a standalone basis and greater than the combined indebtedness of Jazz and GW prior to the announcement of the acquisition. This increased level of indebtedness could adversely affect the combined company’s business flexibility and increase its borrowing costs.
Our inability to maintain or increase sales from our neuroscience therapeutic area would have a material adverse effect on our business, financial condition, results of operations and growth prospects.
The introduction of new products in the U.S. market that compete with, or otherwise disrupt the market for, our oxybate products and product candidates would adversely affect sales of our oxybate products and product candidates.
The distribution and sale of our oxybate products are subject to significant regulatory restrictions, including the requirements of a REMS and these regulatory requirements subject us to risks and uncertainties, any of which could negatively impact sales of Xyrem and Xywav.
While we expect our oxybate products, Xyrem and Xywav, to remain the largest part of our business, our success also depends on our ability to effectively commercialize products in our oncology therapeutic area. An inability to effectively commercialize Defitelio, Vyxeos and Zepzelca and to maximize their potential where possible through successful research and development activities and an inability to replace the future product sales we will lose from Erwinaze, would have a material adverse effect on our business, financial condition, results of operations and growth prospects.
We face substantial competition from other companies, including companies with larger sales organizations and more experience working with large and diverse product portfolios, and the commercial potential of our current products and any future products may be reduced or eliminated if our competitors develop or acquire and commercialize
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generic or branded products that are safer or more effective, are more convenient or are less expensive than our products.
Adequate coverage and reimbursement from third party payers may not be available for our products and we may be unable to successfully contract for coverage from pharmacy benefit managers and group purchasing organizations, which could diminish our sales or affect our ability to sell our products profitably; conversely, to secure coverage from these organizations, we may be required to pay rebates or other discounts or other restrictions to reimbursement that could diminish our sales.
The pricing of pharmaceutical products has come under increasing scrutiny as part of a global trend toward healthcare cost containment and resulting changes in healthcare law and policy may impact our business in ways that we cannot currently predict, which could have a material adverse effect on our business and financial condition.
In addition to access, coverage and reimbursement, the commercial success of our products depends upon their market acceptance by physicians, patients, third party payers and the medical community.
Delays or problems in the supply of our products for sale or for use in clinical trials, loss of our single source suppliers or failure to comply with manufacturing regulations could materially and adversely affect our business, financial condition, results of operations and growth prospects.
Our future success depends on our ability to successfully develop and obtain and maintain regulatory approvals for our late-stage product candidates and, if approved, to successfully launch and commercialize those product candidates.
We may not be able to successfully identify and acquire or in-license additional products or product candidates to grow our business, and, even if we are able to do so, we may otherwise fail to realize the anticipated benefits of these transactions.
Conducting clinical trials is costly and time-consuming, and the outcomes are uncertain. A failure to prove that our product candidates are safe and effective in clinical trials, or to generate data in clinical trials to support expansion of the therapeutic uses for our existing products, could materially and adversely affect our business, financial condition, results of operations and growth prospects.
We have incurred and may in the future incur substantial costs as a result of litigation or other proceedings relating to patents, other intellectual property rights and related matters, and we may be unable to protect our rights to, or commercialize, our products.
Our business is currently adversely affected and could be materially and adversely affected in the future by the evolving effects of the COVID‑19 pandemic and related global economic slowdown as a result of the current and potential future impacts on our commercialization efforts, clinical trial activity, research and development activities, supply chain and corporate development activities and other business operations, in addition to the impact of a global economic slowdown.
Significant disruptions of information technology systems or data security breaches could adversely affect our business.
We are subject to significant ongoing regulatory obligations and oversight, which may result in significant additional expense and limit our ability to commercialize our products.
If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.
We have incurred substantial debt, and expect to incur additional debt in connection with the GW Acquisition, which could impair our flexibility and access to capital and adversely affect our financial position, and our business would be adversely affected if we are unable to service our debt obligations.
To continue to grow our business, we will need to commit substantial resources, which could result in future losses or otherwise limit our opportunities or affect our ability to operate and grow our business.
Additional discussion of the risks, uncertainties and other factors described above, as well as other risks material to our business, can be found under “Risk Factors”detail in Part I, Item 1A of the 2020our Annual Report on Form 10-K.10-K for the year ended December 31, 2021. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements. Also, these forward-looking statements represent our plans, objectives, estimates, expectations and intentions only as of the date of this filing. You should read this Quarterly Report on Form 10-Q10‑Q completely and with the understanding that our actual future results and the
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timing of events may be materially different from what we expect. We hereby qualify our forward-looking statements by our cautionary statements. Except as required by law, we undertake no obligation to update or supplement any forward-looking statements publicly, or to update or supplement the reasons that actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.

Item 3.Quantitative and Qualitative Disclosures About Market Risk

During the three months ended March 31, 2021,2022, there were no material changes to our market risk disclosures as set forth in Part II, Item 7A “Quantitative7A“Quantitative and Qualitative Disclosures About Market Risk” in our Annual Report on Form 10-K for the year ended December 31, 2020.2021.

Item 4.Controls and Procedures
Evaluation of Disclosure Controls and Procedures. We have carried out an evaluation under the supervision and with the participation of management, including our principal executive officer and principal financial officer, of our disclosure controls and procedures (as defined in Rule 13a-15(e) of the Securities Exchange Act of 1934, as amended) as of the end of the period covered by this Quarterly Report on Form 10-Q.10‑Q. Based on their evaluation, our principal executive officer and principal financial officer concluded that our disclosure controls and procedures were effective as of March 31, 2021.2022.
Limitations on the Effectiveness of Controls.Controls.  A control system, no matter how well conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are met. Because of inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that all control issues, if any, within an organization have been detected. Accordingly, our disclosure controls and procedures are designed to provide reasonable, not absolute, assurance that the objectives of our disclosure control system are met and, as set forth above, our principal executive officer and principal financial officer have concluded, based on their evaluation as of the end of the period covered by this report, that our disclosure controls and procedures were effective to provide reasonable assurance that the objectives of our disclosure control system were met.
Changes in Internal Control over Financial Reporting.Reporting.  During the quarter ended March 31, 2021,2022, other than continuing changes to our internal control process resulting from the acquisition of GW, there have been no changes to our internal control over financial reporting that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

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PART II – OTHER INFORMATION

Item 1.Legal Proceedings
The information required to be set forth under this Item 1 is incorporated by reference to Note 11,9, Commitments and Contingencies—Legal Proceedings of the Notes to Condensed Consolidated Financial Statements included in Part I, Item 1 of this Quarterly Report on Form 10-Q.10‑Q.

Item 1A.Risk Factors
There have been no material changes to the risk factors as previously disclosed in Part I, Item 1A in our Annual Report on Form 10-K for the year ended December 31, 2020.2021.
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Item 2.Unregistered Sales of Equity Securities and Use of Proceeds
Issuer Purchases of Equity Securities
In November 2016, our board of directors authorized a share repurchase program and as of March 31, 20212022 had authorized the repurchase of ordinary shares having an aggregate purchase price of up to $1.5 billion, exclusive of any brokerage commissions. Under this program, which has no expiration date, we may repurchase ordinary shares from time to time on the open market. During the three months ended March 31, 2021,2022, we did not repurchase any of our ordinary shares. As of March 31, 2021,2022, the remaining amount authorized under the share repurchase program was $431.2 million.
Under our share repurchase program, we are authorized to repurchase shares from time to time through open market repurchases. Such repurchases may be pursuant to Rule 10b-18 or Rule 10b5-1 agreements as determined by our management and in accordance with the requirements of the Securities and Exchange Commission.

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Item 6.Exhibits
Exhibit
Number
Description of Document
2.1
2.2
2.3
2.4
2.5
2.6†
2.7†
2.8
2.9
2.10‡
3.1
4.1
4.2A
4.2B
4.3A
4.3B
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4.4A
4.4B
4.5A
4.5B4.2B
4.2C
10.1#
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31.1
31.2
32.1*
101.INSXBRL Instance Document - The instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document
101.SCHInline XBRL Taxonomy Extension Schema Document
101.CALInline XBRL Taxonomy Extension Calculation Linkbase Document
101.DEFInline XBRL Taxonomy Extension Definition Linkbase Document
101.LABInline XBRL Taxonomy Extension Labels Linkbase Document
101.PREInline XBRL Taxonomy Extension Presentation Linkbase Document
104Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101)
__________________

+    Indicates management contract or compensatory plan.
†    Confidential treatment has been granted for portions of this exhibit.exhibit (indicated by “[*]”). Omitted portions have been filed separately with the SEC.
#    Portions of this document (indicated by “[***]”) have been omitted because they are not material and are the type that the Company treats as private and confidential.
‡    Certain portions of this exhibit have been omitted pursuant to Item 601(b)(2) of Regulation S-K.
*    The certification attached as Exhibit 32.1 accompanies this Quarterly Report on Form 10-Q10‑Q pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, and shall not be deemed “filed” by the Registrant for purposes of Section 18 of the Securities Exchange Act of 1934, as amended.
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
Date: May 4, 20212022
 
JAZZ PHARMACEUTICALS PUBLIC LIMITED COMPANY
(Registrant)
/s/ Bruce C. Cozadd
Bruce C. Cozadd
Chairman and Chief Executive Officer and Director
(Principal Executive Officer)
/s/ Renée Galá
Renée Galá
Executive Vice President and Chief Financial Officer
(Principal Financial Officer)
/s/ Patricia Carr
Patricia Carr
Senior Vice President, FinanceChief Accounting Officer
(Principal Accounting Officer)
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