EXHIBIT 99.1
Contact:
Paul V. Maier
Senior VP and CFO
858-550-7573
Abe Wischnia
Senior Director of Investor Relations
and Corporate Communications
858-550-7850
TARGRETIN(R) FAILS TO MEET PRIMARY OR SECONDARY ENDPOINTS IN PIVOTAL TRIALS FOR
FRONT-LINE NON-SMALL CELL LUNG CANCER
SAN DIEGO, Calif.--March 28, 2005--Ligand Pharmaceuticals Incorporated
(Nasdaq:LGND) announced today that its two pivotal Phase III studies of
Targretin(R) (bexarotene) capsules in front-line combination therapy with
standard chemotherapy to treat advanced non-small cell lung cancer (NSCLC) did
not meet their endpoints of improved overall survival and projected two-year
survival. The studies were designed to evaluate whether adding Targretin to
front-line cisplatin/vinorelbine or carboplatin/paclitaxel chemotherapy extends
the survival of patients with advanced (Stage IIIB with pleural effusion or
Stage IV) NSCLC.
In SPIRIT I, patients were randomized to two arms, receiving either
cisplatin/vinorelbine chemotherapy alone or in combination with Targretin
capsules. SPIRIT II enrolled patients to two arms receiving either
carboplatin/paclitaxel alone or in combination with Targretin capsules.
For both studies, the primary endpoint was overall survival and the
secondary endpoint was Kaplan-Meier projected two-year survival. No
statistically significant differences in primary or secondary endpoints in the
intent to treat population were seen in either trial. An initial trend analysis
of sizeable sub-groups in the treatment arms of both trials suggests a
relationship between Targretin dose intensity and biomarker response (i.e.,
triglyceride elevations) with survival, and is the subject of further
evaluations in parallel with other risk factor analysis to better identify the
determinants of benefit or risk to Targretin in a first-line setting.
Both studies recruited patients from both U.S. and international sites,
with SPIRIT I having the largest proportion of patients from outside of North
America and SPIRIT II having the largest proportion of patients from the U.S. A
well-balanced demographic distribution across the two arms was achieved in both
trials, consistent with what has been reported in other similar, large-scale
phase III trials conducted recently in a similar patient population.
The initial daily dose of Targretin in both trials was similar to that used
in prior phase II studies in which a positive trend in survival had been
observed. Doses of carboplatin and vinorelbine in SPIRIT I and carboplatin and
paclitaxel in SPIRIT II were also consistent with standard chemotherapy regimens
used in most recent large-scale trials.
Targretin is a selective retinoid X receptor (RXR) modulator with proven
efficacy as monotherapy in the treatment of cutaneous T-cell lymphoma (CTCL).
RXR levels in the tumor have been shown to be an independent predictor of
survival in NSCLC and in other solid tumors.
"We are very disappointed in the lack of survival advantage of
Targretin/dual chemotherapy triple therapy in first-line NSCLC patients,
particularly in view of the consistent positive trends seen in several phase
I/II studies and in the preclinical data that provided strong mechanistic
support for a potentially beneficial Targretin/chemotherapy combination," said
Andres Negro-Vilar, M.D. Ph.D., Ligand's executive vice president for research
and development and chief scientific officer. "We know that several other
targeted therapies combined with chemotherapy have also fallen short of a
survival advantage in a first-line setting while in some cases proving
efficacious in second- and third-line treatment. We believe SPIRIT I and II
provided robust data to evaluate the value of adding Targretin to combo
chemotherapy in the front-line setting and based upon those results now plan to
continue to evaluate the potential of Targretin to provide benefit for second-
and third-line patients."
In the SPIRIT trials, the addition of Targretin to both chemotherapy
regimens was generally well tolerated. Adverse events were similar to those
previously reported in studies with chemotherapy treatment and with Targretin.
Regarding serious adverse events with an incidence greater than 1%, there was an
increase in the incidence of
neutropenia in SPIRIT I in the Targretin arm principally attributed by the
investigators to combo chemotherapy. An increase in febrile neutropenia was seen
in the chemotherapy control arm of that study. No significant differences in the
incidence of serious adverse events between the arms were seen in SPIRIT II.
Adverse events - grade 3 and 4 - that occurred more frequently with Targretin
included hypertriglyceridemia in both trials, neutropenia, asthenia and
dehydration in SPIRIT II and dyspnea in SPIRIT I. These differences were
recorded for all AEs that reached a level of 5% frequency in any arm.
Ligand will continue to analyze the data and plans to make a detailed
scientific presentation at the upcoming ASCO or other near-term scientific
conferences.
"While this is disappointing news for all stakeholders, we expect to
continue to analyze the data from SPIRIT I and II and apply it to the continued
development of Targretin in NSCLC," said David E. Robinson, Ligand's chairman,
president and CEO. "As a company, we will also remain focused on the near-term
priority of accelerating the commercial development of Avinza(R) and ONTAK(R) as
principal drivers of the company's growth as we await the approval of near-term
corporate partner products."
COMPREHENSIVE CLINICAL TRIAL PROGRAM
Several additional trials are being conducted to further assess the role of
Targretin in combination with different chemotherapy regimens in the first-line
setting. A recently-completed phase II trial evaluated Targretin in combination
with gemcitabine plus carboplatin. A phase I/II trial is evaluating a
dose-escalation schedule of Targretin in combination with weekly carboplatin
plus paclitaxel. A multicenter randomized phase II trial is evaluating Targretin
capsules given either concomitantly to or sequentially after the administration
of weekly carboplatin plus paclitaxel. A phase II study is evaluating Targretin
in combination with taxotere given every three weeks. Two multicenter trials are
evaluating the combination of Targretin plus taxotere as second-line treatment
for relapsed NSCLC.
Three additional trials are being conducted in patients with NSCLC who have
failed at least two prior treatments for their cancer. One multicenter trial is
evaluating Targretin monotherapy in 150 patients with relapsed disease and a
second trial is evaluating the combination of Targretin plus erlonitib
(Tarceva(R)).
Several of the above studies are scheduled for presentation at the
forthcoming ASCO meeting.
ABOUT TARGRETIN
In December 1999, the FDA approved Targretin capsules for the treatment of
cutaneous manifestations of cutaneous t-cell lymphoma in patients who are
refractory to at least one prior systemic therapy. The European Commission
granted marketing authorization for Targretin capsules in March 2001, and the
product is currently marketed in many major European countries, including
Germany, the United Kingdom, France, and Italy.
WEB CAST CONFERENCE CALL
Ligand will host a live web cast, open to all interested parties, of a
conference call during which Ligand management will discuss this news release.
The web cast will be available at http://www.ligand.com (investor relations
page) and at http://www.streetevents.com on March 28, 2005, at 8:30 a.m. Eastern
time (5:30 a.m. Pacific), and will be archived for 15 days.
ABOUT LIGAND
Ligand discovers, develops and markets new drugs that address critical
unmet medical needs of patients in the areas of cancer, pain, skin diseases,
men's and women's hormone-related diseases, osteoporosis, metabolic disorders,
and cardiovascular and inflammatory diseases. Ligand's proprietary drug
discovery and development programs are based on its leadership position in gene
transcription technology, primarily related to Intracellular Receptors. For more
information, go to www.ligand.com.
CAUTION REGARDING FORWARD-LOOKING STATEMENTS
This news release contains forward-looking statements within the meaning of
section 21E of the Securities Exchange Act of 1934, as amended, that involve
risks and uncertainties and reflect Ligand's judgment as of the date of this
release. These include statements regarding data analysis and evaluation of
Targretin, presentations at conferences, continued development and other studies
of Targretin, commercial development of other products such as Avinza and ONTAK,
company growth and approval of corporate partner products. Actual events or
results may differ from our expectations. For example, there can be no assurance
that other studies or evaluations of
Targretin will be favorable or that they will confirm results of previous
trials, that data evaluation will be completed or demonstrate any hypothesis or
endpoint, that any presentations will be made or favorably received, that
Targretin will be useful in new indications alone or in combination with other
drugs, that marketing applications will be filed or, if filed, approved, either
by Ligand or its corporate partners, that further clinical or commercial
development of Targretin, Avinza or ONTAK will be completed or successful, that
the company will be successful in accelerating the commercial development of
Avinza or Ontak or be able to grow its business, nor that any corporate partner
products will be approved. Our stock price may suffer as result of the failure
of these trials to meet their endpoints or if any actual events differ from our
expectations. Additional information concerning these and other risk factors
affecting Ligand can be found in prior press releases as well as in public
periodic filings with the Securities and Exchange Commission, available via
www.ligand.com. Ligand disclaims any intent or obligation to update these
forward-looking statements beyond the date of this release.