Hello and welcome to FibroGen Third Quarter 2018 Financial Results Teleconference Call. My name is Michelle, and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session [Operator Instructions]. Please note that this conference is being recorded. I will now turn the call over to Ms. Karen Bergman. Ma'am, you may begin.
Thank you, Michelle. And thank you everyone for joining us this afternoon. Today, we are reporting financial results and corporate updates for the third quarter of 2018.
Joining me on the call today are Tom Neff; Chairman and Chief Executive Officer; Dr. Peony Yu, Chief Medical Officer; Ms. Christine Chung, Senior Vice President China Operations; Dr. Elias Kouchakji, Senior Vice President Clinical Development, Drug Safety and Pharmacovigilant; and Mr. Pat Cotroneo, Chief Financial Officer.
Following our prepared remarks, Tom will discuss upcoming milestones and will open the call to Q&A.
During this call, we may make forward-looking statements regarding our business, including our collaborations with AstraZeneca and Astellas; financial guidance; the initiation, enrollment, design, conduct and results of clinical trials; our regulatory strategies and potential regulatory results; our research and development activities and certain other business matters.
For risks and uncertainties regarding our business and statements made on the call today, as well as factors beyond our control that may cause differences between current expectations and actual results, we refer you to our Annual Report on Form 10-K for the fiscal year ended December 31, 2017, and our Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2018, filed with the Securities and Exchange Commission. Copies of these filings can be found in the Investors Section of our website. We undertake no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise. The format for today's call includes remarks from FibroGen's management team, and then we will open the lines to take your questions. The press release reporting our financial results and business updated and a webcast of today's conference call can be found on the investors section of FibroGen's website at www.fibrogen.com. The webcast will be available for two weeks from to date. And with that, it's my pleasure to turn the call over to our CEO, Tom Neff.
Good afternoon. Thank you for joining us.
Let's begin with the exciting progress in our roxadustat program. We now have 9 of the 15 Phase III studies data locked and completed two in China, five in Japan and two in Europe. One study in Japan is still ongoing. We're now in the process of carefully planning out the unblinding and release of five Phase III studies conducted by FibroGen and AstraZeneca representing the core of the U.S. NDA.
Our timeline includes collection of relevant data, completion of adjudication, unblinding, and finally the MACE pooling analysis for each of the dialysis and non-dialysis population's increasingly the focus of our project teams is to have a Mason analysis completed by March, April next year. In order to complete the March, April 2019 in order to complete the NDA filing by the end of June of 2019. Later on this call, Dr. Peony Yu, will discuss the process for reporting on these Phase III trials and the adjudication and pooled analysis. I would like to take a moment to highlight, patient populations that I am excited about that are coming to the point of reviewing results. The incident dialysis population that has never been systematically studied in CKD anemia as well as the placebo study in patients that have hard to treat anemia in stage 4 CKD anemia.
First, we'll report results in over a thousand patients and incident dialysis.
The first ever will control comparison anemia therapies in dialysis. Prior studies that relied on fully stabilized team or peritoneal dialysis, patients who had been treated with ESA to achieve stable hemoglobin and anemia correction for many months, if not years before entering a trial. Thus, these studies included the best responders to recombinant rhEPO which we believe is a narrow population, probably only addressing about half of the total dialysis initiation pool in the real world. The special responders to rhEPO are overrepresented in the control pool as a function of study design. We believe that a significant portion of the general dialysis population has to date not been studied.
Now we have the opportunity to properly compare to conceptually distinct approaches to anemia therapy as well as having the opportunity to demonstrate a treatment benefit for roxadustat in this broader population.
Second, our U.S. non-dialysis study versus placebo has been conducted in a population after broad ECUs in non-dialysis sittings had been restricted. And hemoglobin levels in entry are much lower than prior studies would have allowed.
Our study is unique and that there are no well-controlled large CKD patients studies where large components of the patient population is in stage four and stage five, including large number of single-digit eGFR patients at baseline. In effect, this study measures the benefit of anemia therapy and what is now called the peri-dialysis population. With both of these study areas, I know there is a large audience of physicians, regulators, patients that are interested in seeing results from these study designs as the information will greatly increase the understanding of these patients with later stage renal disease. In October, we and our partners presented four studies at ASN kidney Week 2018 in San Diego. There were three posters and an oral presentation for fourth, all presented roxadustat Phase III data from China and Japan. It happened at our final meetings with our Chinese regulators, the CDE, we're scheduled on very short notice and face-to-face sessions in Beijing between travel, the briefing documents and the meetings in the Beijing and the core anemia team could not be at ASN.
As a result, there was not much time for the team to address the follow-up to the poster sessions.
As I assess the situation, I saw a lot of very smart people getting the wrong message on certain data. Normally I'd view this as a breaks of the game in the U.S., but in this situation, the real issue for investors and analyst as well as any data from China or Japan representing real safety signal relevant to the upcoming global program readouts. Thus I instructed our teams to provide clear and concise explanations to help investors and analysts to understand what the rationales based in fact are not going to support a safety signal in the global program. Dr. Peony Yu will address these assessments and explanations later on his call.
As you know, roxadustat is the most advanced candidate in the HIF-PHI class worldwide. And we expect approval for this first-in-class oral anemia therapeutic and dialysis with or without prior ECUs by year end in China.
We are completing final steps in a rigorous review process including multiple regulatory agencies and covering all of our clinical and non-clinical and manufacturing data.
We also expect NDD, or non-dialysis to be approved as part of the label.
However, the timing is pending from scheduling for clinical site inspections by the CFDI. Many of you may know CFDI is experiencing backup in their scheduling, so we're not quite sure at what point in the first half of the year will get inspected. Chris Chung, our Managing Director for FibroGen in China will provide updates on where we are in completing the final steps in the approval process for roxadustat in China. Equally exciting for the FibroGen anemia team, the roxadustat NDA was filed in Japan in September by our partner Astellas for the treatment of patients on dialysis who are suffering from anemia associated with CKD. Peony will speak more about the new data presented at ASN on two of the four Japan Phase III trials in dialysis-dependent patients. These studies were sponsored by Astellas. I would now like to turn the update to Pamrevlumab.
Our Pamrevlumab program which centers on the understanding of the biology of fibrosis and the role of CTGF and various diseases and systems is proprietary to FibroGen, our first-in-class anti-CTGF agent. Pamrevlumab targets mechanisms involved in fibrosis progression related diseases such as idiopathic pulmonary fibrosis, pancreatic cancer, and Duchenne muscular dystrophy. In each area we are seeing potential for unique therapeutic benefit for patients otherwise facing high mortality risks. We completed our Phase II meetings with the FDA where we reviewed and came to agreement on Phase III study designs for Pamrevlumab both in IPF and locally advanced unresectable pancreatic cancer or LAPC.
Our teams are planning on commencing enrollment in our Phase III LAPC study in the first quarter of 2019, followed shortly by our Phase III IPF study. Pamrevlumab has demonstrated anti-fibrotic activity by reversing or slowing fibrosis in IPF and improving the resectability and resection rates in LAPC, no safety signals have been identified in preclinical and clinical evaluation to-date. Both of these programs have been granted Fast Track designation by the FDA. I must also note our program and non-ambulatory Duchenne muscular dystrophy. We believe there may be an important and much needed role for Pamrevlumab and DMD, which is the most common and severe form of muscular dystrophy and where there is significant ongoing fibrosis causes impairment of cardiovascular and pulmonary systems as well as severe decline of muscle strength. All 21 patients in our Phase II pilot study will complete one-year of treatment in March and we will be able to announce data from that study at that time. Dr. Elias Kouchakji will talk about these two Phase III Pamrevlumab studies and our DMD program later on the call.
Let me finish here by addressing finance, as of September 30, 2018 FibroGen had $722 million in cash. NDA for roxadustat was submitted in Japan by our partner Astellas for anemia associated with dialysis-dependent CKD in September, triggering a $15 million milestone payment to FibroGen from Astellas.
For accounting purposes, this is largely recognized as revenue last quarter based on current GAAP rules.
In addition, we have additional cash on hand being reported as a result of sales in roxadustat study EPI to Astellas for commercial use in the Japanese market. That will provide more details on this development as well as our cash position and our year-end projections later on this call. I would now like to turn the mic over to Dr. Peony Yu, for updates on the anemia program. Peony, please go ahead.
Thank you, Tom.
As Tom said, it's a busy and exciting time for the roxadustat program and I'd like to first talk about progress in China and Japan, highlighting the four Phase III studies recently presented at the ASN Kidney Week, then our progress in the U.S. and EU program.
As you know, we are pursuing for parallel regulatory pathways. China NDA review by CDE has been going very well as Chris Chung will discuss further. And the Japan NDA was filed with the PMDA in September. At the ASN Kidney Week in October, there were four roxadustat Phase III studies presented. Two from the China Phase III studies designed to meet China domestic approval requirements and two from the four Phase III studies, which are part of the Japan and NDA package.
For clarity, these studies are not part of the MACE analysis for the U.S. and EU packages and would not design nor power to draw conclusions about cardiovascular outcomes.
We have come across a few questions around these presentations, particularly whether certain data from the China or Japan might be a safety signal for the global program. I would like to provide clarification in three areas, and then I shall discuss key takeaways from these four positive Phase III trials.
First was, as to mortality rates being in the two studies to provide context, patients with end-stage renal disease requiring dialysis unknown to have significant comorbidities and high mortality risk. The considerable data available on dialysis patients from government sponsor registries and academic publications provide helpful background rates. Dialysis registries in Japan and China have shown the annual mortality rate in dialysis patients to be 9% to 10% and 6.8% to 8.2% respectively. And in the U.S. it is approximately 17%, according to USRDS. It was 10.3% annually in the [Montese] Phase III study. The annualized mortality rates in our China and Japan dialysis studies was only 2%, which is much lower than the reported rate in these publications. The extremely low rate of 2% reported in these small studies should not be seen as a signal as it is much lower than the historical rates with ESA in the similar patient population, nor is it predictive for the much larger U.S./EU outcome trials in which many hundreds of events are require for statistical powering.
Second, in the China studies, while there was an apparent imbalance in adverse event reporting by investigators have hyperkalemia and metabolic acidosis.
As we reported at ASN, no imbalance of potassium or bicarb abnormality between treatment arms was found in the central lab data for these studies. Rather, these lab values for the study are consistent with an characteristic of the chronic kidney disease patient population where the diseased kidneys were no longer able to properly regulate potassium levels and acid base balance even before study participation. These data have been review with the Phase III lead investigators, CFDA inspectors and CDE as part of the NDA review. Based on our analysis of the data, we conclude there was no causal relationship between roxadustat use and these - abnormal laboratory values in potassium or bicarbonate level. More over a similar imbalance of these events have not been reported in the other completed studies. We therefore believe there is no basis to view this as a signal or to expect this to be an issue in the global program.
Finally, I would like to explain the higher rate of early study discontinuation in roxadustat arm compared to EPO in the open label China dialysis study. We believe this result largely from the inherent bias against an experimental agent when compare with standard of care in an open label study design. This often leads to a symmetric dropout rates in the experimental arm where investigators have more experience and patients are more familiar with the standard of care. In contrast, neither is the Japan dialysis study, not a China non-dialysis study, both of which are double-blind it showed this kind of differential dropout rate.
In addition, in this study, patients in the comparator arm were provided with a premium Killen Amgen, EPO, which costs three times the price of the usual knockoff EPO that they typically receive understand that reimbursement for dialysis patients. And this factor with perceived value in the higher value in the study comparator drug could have further contributed to the difference in discontinuation rates between the treatment arms. We hope this information is helpful.
Now, let me turn to the major results. Overall, we have had several positive findings in the China and Japan studies. Primary efficacy endpoints were met with acceptable safety profile and the results are part of China NDA as well as Japan NDA.
We are excited about the progress in China NDA review on which Chris will provide more details in a few minutes. Of note, it is exciting to see roxadustat superior efficacy over EPO in the subset of inflamed patients in the China dialysis study. Without incremental dose requirement in the subgroup of patients with elevated CRP. This differentiation some ESA in overcoming EPO hypo responsiveness, which is at ESA's Achilles' heel is expected to be translated into safety benefit over EPO in larger studies, powerful cardiovascular outcome evaluation.
We are eager to see U.S./EU data for this thesis. In Japan, Astellas has submitted NDA for CKD anemia in dialysis patients that included the four positive Phase III dialysis studies and has announced completion of one of the two Phase III CKD non-dialysis studies with plans to submit supplemental NDA upon completion of the second non-dialysis Phase III study in Japan.
Turning to the much larger U.S./EU roxadustat program, which is designed and powered for cardiovascular safety evaluation. There are over 9,000 patients of whom over 6,000 had already been on the study for over a year. These studies have been undergoing periodic safety review by treatments by the independent DSMB for over four years. The most recent DSMB review was on August 1, 2019 with recommendation of continuing per protocol just like their assessments in all prior reviews. We and our partners have completed patient treatment in the seven Phase II roxadustat CKD anemia study supporting U.S. NDA and European MAA.
Astellas has reported positive topline result on the first global Phase III placebo-controlled study in CKD patients not on dialysis, and has also completed currently a Phase III dialysis study in Europe. I like to take a moment to outline that data readout and submission timeline of the U.S./EU roxadustat program.
We are currently planning to report the rest of the individual Phase III topline study results in CKD anemia in the fourth quarter of this year. This is for both dialysis and non-dialysis dependent patients.
We are on track to reporting adjudicator pool results and submission of U.S. NDA in the first half of 2019 in collaboration with AstraZeneca, our U.S. Working with Astellas, we are also preparing to work together on the MAA submission in Europe in 2019. I'd like to now turn the call back to Tom.
Thank you, Peony. Chris Chung, our Head of China Operations will now share updates on our current activities and regulatory progress. Chris, please go ahead.
Thank you, Tom.
We are progressing towards market approval in China. In the last quarter, we successfully completed an expert review meeting, which is a critical step in the approval process. Efficacy and safety data, the label and post-approval commitments for both dialysis and non-dialysis were addressed with the Center for Drug Evaluation or the CDE, the technical review arm of the NMPA in a presence of external experts. We successfully completed pre-approval manufacturing inspections by the China Food and Drug Inspections, CFDI of both API and drug product. We successfully completed analytical testing of samples produced by FibroGen China at the national testing agency, the National Institute of Food and Drug Control, also known as the NIFDC. We believe we're very close to roxadustat approval by the NMPA in the treatment of anemia and chronic kidney disease in both dialysis and non-dialysis.
For dialysis dependent patients, we completed the clinical site inspections in the second quarter of this year.
While there is no equivalent of a PDUFA action date in China, we anticipate approval for dialysis by year end. The dialysis label will cover both hemodialysis and peritoneal dialysis and regardless of whether they have been ESA-treated or ESA-naïve.
For non-dialysis, we are waiting in queue for clinical site inspections to be completed.
We expect to be able to expand the label to include non-dialysis in the first half of 2019. Thank you again for your time. Tom?
Thank you, Chris.
Turning to Pamrevlumab, in our IPF Phase III study, we are targeting a significant untreated population of patients who are currently on non-standard of care. I would like to ask Dr. Elias Kouchakji to discuss our three Pamrevlumab programs in IPF, Pancreatic Cancer and DMD. Elias, please go ahead.
Thank you, Tom. Starting with IPF, we have presented clinical and preclinical data this quarter at the European Respiratory Society International Congress, ERS and 20 International Colloquium on Lung and Airway Fibrosis, ICLAF. The data highlights, the positive safety and efficacy results from our Phase IIb study PRAISE. Pamrevlumab demonstrated statistically significant attenuation of fibrosis as measured by FVC and quantitative HRCT, and they're statistically significant advantage in disease progression defined as a decline in FVC percent predicted of 10% or death.
Following our end of Phase II meeting with the FDA, we are planning a placebo-controlled double-blind Phase III study similar in design to our PRAISE Phase IIb study.
We have planned to enroll approximately 500 patients who are currently not on standard of care. The primary endpoint for this trial will be changed in FVC from baseline.
Moving onto LAPC, in the first quarter of 2019, we will initiate a randomized double-blind placebo-controlled Phase III study, evaluating Pamrevlumab therapy in combination with gemcitabine and nab-paclitaxel as a neoadjuvant treatment. We planned to enroll approximately 260 patients in this study. This study is a similar design to our Phase II trial in which will assess resectability and resection was a primary endpoint of overall survival. At the end of the treatment period, we will evaluate the resectability and resection rate and should the resection rates favor the Pamrevlumab combination arm, we will request a meeting with the FDA to discuss a marketing application under the provision of accelerated approval. In this study, we will also continue to follow patient for overall survival.
Now, I'd like to move to that DMD program. This is another important program for Pamrevlumab.
Our Phase II study in Duchenne muscular dystrophy is progressing very well. In September during the World Muscle Society in Mendoza, Argentina, there was considerable interest in Pamrevlumab from the scientific and clinical community, and from the patient advocacy groups.
Our Phase II study is evaluating 21 nonambulatory young patients over a three year timeframe.
As I mentioned, old patient will have completed one full-year of Pamrevlumab treatment by the end of the first quarter of 2019. We plan to update on the progress of this study in the second quarter. And I would like to say in summary, we are excited to be advancing Pamrevlumab into late stage clinical development and to be working on the first-in-class therapeutic candidate was potential to help patients with these serious in life threatening conditions. Thank you for your time today. And Tom, I will turn the call to you.
Thank you, Elias. Pat Cotroneo, our Chief Financial Officer will now discuss financial highlights for the third quarter of 2018. Pat, could you go ahead please.
Thank you, Tom.
As announced today, total revenue for the quarter ended September 30, 2018 was $29 million as compared to $40.6 million for the third quarter of 2017.
For the same period, operating expenses were $71.8 million and net loss was $42.6 million or $0.50 per basic and diluted share.
As compared to operating expenses of $63.3 million, a net loss of $24.5 million or $0.32 per basic and diluted share for the same period in the prior year. Included in operating expenses for the quarter ended September 30, 2018 was an aggregate non-cash portion totaling $16 million of which $14.3 million was a result of stock-based compensation expense as compared to an aggregate non-cash portion totaling $11.5 million of which $9.6 was a result of stock-based compensation expense for the same period in the prior year.
As of September 30, 2018, we had $722.6 million in cash as compared to $733.7 million at the end of Q2, 2018.
For these purposes, total cash refers to cash, as well as cash equivalents, receivables, investments, consisting primarily of investment grade corporate debt and restricted time deposits related to our building lease.
We are currently projecting a year-end cash balance in the range of $720 million to $730 million. This has increased from our previously disclosed range of [$650 to $670] due primarily to an anticipated shipment to Astellas of drug supply totaling approximately $42 million in support of anticipated 2019 pre-launch activities in Japan. Thank you. And I would now like to turn the call back over to Tom.
Thank you, Pat. It has been an incredibly busy and an exciting year FibroGen people year-to-date.
We have had 15 Phase III studies employee and we're launching two major Phase III programs. I'd like to run through important upcoming developments and milestones for the Company. Try to keep it simple as much as possible. Starting with roxadustat we plan to report Phase III topline study results for roxadustat. Q4 and we're really focusing on trying to get the MACE reported out by March, April time period in 2019.
We are expecting to submit U.S. NDA for roxadustat for the treatment of anemia and dialysis dependent non-dialysis dependent CKD in the first half of 2019. And we will also be supporting the filing of the MAA by Astellas in Europe in the same time periods. In China, we anticipate a market approval decision for roxadustat and dialysis this is dialysis without a restriction on prior EPO use and we expect the second part of the label NDD to be approvable upon completion of inspections, which would be probably Q2 of 2019.
So the first half we're looking right at year-end dialysis and NDD a few months into 2019. In Japan, for the dialysis filing, we expect to regulatory review within a year. We're entering into a period of significant upscaling for Pamrevlumab program related in part to the Phase IIIs and part to the scaling production technology for commercial activity. And locally advanced pancreatic cancer we will be commencing enrollment in our Phase III study in the first quarter of 2019.
Sometime very close to that we will also be initiating our Phase III IPF study. These were on parallel tracks with different teams. And DMD, which I think will become a very important narratives time goes on. We're looking forward to completing one-year full-year - one full-year treatment at the end of first quarter 2019. With that, I'd like to turn this call back over to Karen for Q&A. Karen please.
Thank you, Tom. And Michelle, if you could kindly open up the line for questions. Thank you.
We will now begin the question-and-answer session. [Operator Instructions] The first question, the cue comes from Difei Yang with Mizuho Securities.
Your line is open. Please proceed.
Hi. Good afternoon and thanks for taking my questions and congratulations on the lot of progress over the year.
So just a couple, first one on MACE.
Just trying to help us to frame what we should be expecting on the upcoming data? We looked at the Japanese patient population, the mortality rate was roughly about 1.3 sounded like per literature and per previous clinical trials, mortality rate especially for the Astellas patients for the EU and the U.S., that we should be expecting a number that is much bigger than 1.3.
Just wanted to confirm if that's the right way to think?
Difei, hello. Nice to hear from you.
Let me try to clarify this a little bit. In Japan, we filed four studies for the NDA. I don't know if you're counting all other than the 1.3 number or not, but nevertheless the 1.3 is very similar to what we've seen for combined Japan, China.
So what we know from the Japan dialysis society website that tracks mortality, is the annual mortality rate which is a rate of mortality per 100 patient exposure. That's how they express it is between 9% and 10% annually for many years going back in time.
And so I think that that's a very useful data point.
Second, it is true the USRDS is much higher 16% or 17%.
I think you may have mentioned this in your recent research report in some way.
You have also provided some other citations in this area. We look at the China, there's a few different surveys and we've also had our sites provide real world data and the range is low of 6.5% and up to 11% or 12% depending on which study you're looking at. The Beijing dialysis registry is 8% and 6.5% for up to the first six years in dialysis that's what I recall. The way we looked at this issue is that our responsibility and accountability right now is to clarify if the data in China or Japan, which is proving to be acceptable in China and we hope this is acceptable in Japan, whether it reach out on the global program for safety signal.
And so I think it's very clear that we don't have a basis to say that at 1.3 or in the totality right around 2% this rate over 100-year PEY exposure denominator.
So that's one answer. And then the second part is that because we have a low rate, we don't quite know what that means in the longer run. It might mean as we enroll more patients and gain more power and look at the U.S./EU data that we have an outstanding rate, but we don't know that right now.
So we're not able to use it as a predictive tool at 2%. We can just simply say we've had 600 patients in studies and we're looking at mortality rates at 2%. This goes directly to investor concern whether East Asia data would read it as a signal on our MACE safety endpoints because death is 70% of the MACE composite.
So it is right on the money in terms of being relevant.
Okay. Thank you Tom for that additional color. And then just turning to Pamrevlumab, so the IPF study and Pancreatic Cancer study were both start early next year, would you guide us roughly what's the timeframe? What's the readouts?
Your question is when we think we get to Phase III readouts?
I think it's a little bit early right now for us to do that.
We will have a better sense of this next year. We do not expect it's one or two years. It'll be longer than that from the time of enrollment. But how much longer remains to be calibrated carefully.
Okay. Thank you.
Okay, good. Thank you.
Thank you. The next question in the queue comes from Terence Flynn with Goldman Sachs. Please proceed.
Hi. This is Gavin on for Terence. I just had a quick question regarding MACE. When the readout comes, should we expect both the DD and NDD populations to readout and will you provide any clarity on secondary endpoints? If so, which secondary endpoints are you guys focused on? Thank you.
So, let's do this in step-by-step. We first have to unblind studies.
So there's five between ourselves and AstraZeneca that we're hoping can get done in December. And then after that we have certain procedures to work through to get the MACE data from these studies properly looked into the software to evaluate comparison. One comparison is versus placebo and non-dialysis, and the other ones versus ESAs in dialysis. We do not know now whether we will be trying to pronounce any of these results. The unblind five studies or the two MACE pools on a tight, same day type of disclosure. Right now we are assuming that's going to probably too difficult to do, and so we may day-on-day rather than all at once.
However, the planning for this is in scheduled in meetings later this month and early next month with AstraZeneca.
So that will probably have more information, more color on exactly how we do the underlines and the pool reporting. There is considerable other data that's being generated. On this point, I would like to ask Peony to assess what she expects in terms of when anything would read out. Peony, could you address that please?
Tom, thank you. Gavin, you asked an excellent question, other than the primary efficacy endpoint of change in hemoglobin from baseline in non-dialysis has compared to placebo and in dialysis is in comparison, what active control using report on Alpha.
Now you're aware of our pool cardiovascular analyses that we expect to read out for MACE. And additional or secondary endpoints, which are also very important would be a MACE plus and with the rubber hits the road will be for hospitalization rate in both pools of patients. I am particularly excited about the opportunity to make a big difference and be able to show such difference in a placebo controlled setting in non-dialysis. And when we are combining the study, we will have a quite a bit of power and by hope for the Holy Grail will be to slowdown being a progression by measuring eGFR changes. And we would also like to demonstrate an improvement in patient's quality of life.
And so there are a number of others, but I'm not going to go through the entire list, but these are the ones that are most important in these patient populations.
So Tom, you want me to state whether the readout on the secondary endpoint will be the same time with individual study or MACE data.
We are still coordinating the data analysis with our partners because it is from these results will be coming from a studies conducted by us, by Astellas and AstraZeneca.
So in our next call, we will be able to provide a more granularity on timeline of announcing these exciting results.
Gavin, do you have any other questions please?
Thank you. That was very helpful. Maybe one more on a Pamrevlumab, just the IPS trial design, when should we expect additional details for that in terms of maybe exclusion inclusion criteria? Thank you.
So let me turn this question over to Elias. Dr. Kouchakji, could you explain status here?
We are in currently and finalizing the protocol and we will be submitting this set to the agency to get their final blessing very soon. When as soon after we will be putting this into the clintrial.gov where all these additional inclusion and exclusion criteria, but I just want to repeat this study will be closely similar to our PRAISE study.
So there is will be not major differences between our inclusion and exclusion criteria than what we have enrolled in our O67 Study PRAISE.
Thank you very much.
Thank you. And the next question in the queue comes from Geoffrey Porges from Leerink Partners.
Your line is open.
Thank you very much. Two quick questions.
First, Peony, it sounds like you have some effective unblinding in the placebo controlled study in China. I am wondering if you could tell us what procedures you have in place to ensure that you won't have any such unblinding in the U.S. study that's going to read out shortly? And then secondly, on Pamrevlumab, the total study size that you're discussing is substantially smaller than that was completed for the other drugs that have been approved in the indication? Can you help us understand whether how we should be confident that the 500 patient study will be sufficient when the incumbents of studied in the range of a 1,000 to 1,500 patients in two different trials in most cases? Thanks.
So Peony, go ahead and explain in China which study was blinded in which one was unblinded to clarify.
So in China the dialysis study was open label, that's the 304 patients study two to one randomization and will compare to arm treated for 26 weeks.
Now for the non-dialysis study, the blind the period was only limited to first eight weeks, because the Chinese regulator for that it was not ethical to maintain patients on placebo to long and the patients in the placebo arm were crossover to active for - and were treated for 18 weeks.
So that both our patients will have an opportunity to be treated for a total of 26 weeks. And then a subset of these patients who enrolled first and to extension to have 52 weeks total.
Now, the difference from this in the U.S. European global program, they are three non-dialysis study conducted one by us and the other two by each of our two partners were the blind as well as the placebo control or maintain throughout the entirety of the study. And it was an event driven trial.
So I'm very up - with variable treatment duration.
So the patients were treated anywhere from one-year for two, three years.
Peony thank you. Elias, maybe you can address the rational for IPF trial design that we've developed.
Tom, I can say understand the question is about this study, the size of this study.
Just like to remind that we run already two Phase II studies or Phase IIa and Phase IIb. The Phase IIb specifically, which is a placebo controlled and the result was statistically significant and the size of this study and the data from this study provided us enough data to have a statistical plan to power the study to be able to meet the statistical analysis that could meet the regulatory requirement for approval. This statistical was reviewed by the agency and the number of the subjects or was I agreed by the agency.
So comparing to other programs that they did not have a sizable study similar to the Phase IIb, our PRAISES study that has led to our understanding how this can remind everyone that this is - in a pirfenidone.
One of this study have failed the statistical analysis I think we are at this time in a position to understand our data.
So Elias, that's helpful. Perhaps you could also, I think he's asking the question about given somebody else's doing 3,000 or 4,000 patients in Phase III? Why the rationale for us results in the 500 patients size?
As an agenda the other company was finding that this large 1,500 size of patient plus they don't have a Phase II with statistical positive results similar to our PRAISE study. That is by itself it is the most valuable tool that we have. And the same time, we have this - not only we're seeing this in the FVC percent predicted and FVC volume, we have seen it on our QSR analysis. At the same time we have [indiscernible] progression to avoid taking all this totality of evidence.
We are able to build this power with sufficient - with this number of patients.
So I think the other aspect Elias that you mentioned is that our discussions with FDA, we had several expert advisors who have spoken. It's very clear that a minority of population in the U.S. for reasons that Eliascan explain it, simply won't use the existing on market medications. And as a result, the statement could be made that there is on the order of 30% to 40% time numbers of patients who have compelling unmet medical need is urgent in character, and there is presently no way for them given the circumstances to be treated. And as it relates to any scenario where we combine with the currently approved products, we inherit their safety profile. And the problem with those safety profiles is that there are lots of issues that cause in a portion of the patients that are unable to use those other medicine. Elias perhaps showed that just a little more there.
Thank you, Tom. This is an important point to emphasize. Pamrevlumab has been - we have over 500 close to 600 patients exposed on this product.
Some of these patients up to five years, we have not identified safety signals.
So this has compared to other approved product, the safety signals are totally different. A good number of patient populations who are being treated the standard of care and they are dropping off the treatment.
Additionally, some of them are not responding to the treatment. The quality of life that is affected either from skin reaction or the sensitivity or the liver enzymes changes, which is a serious and fatal.
So all these are a - the big differences that is added to our population.
Additionally, we know that there is a population that they are rejecting the treatment, although they all lead the population themselves from prescribers who are not eager to prescribe based on the safety profile of this molecule.
As you said there is 40% plus are not treated and they need a therapy that's why this study will provide this tools to prescribers to be able to treat this population that will have nothing else to be treated with.
We'll leave it there. We'll talk more next quarter maybe.
Next is Joel Beatty.
Yes, Joel Beatty with Citigroup.
Your line is open.
Okay. And thanks for taking the questions and all the helpful updates throughout the call.
On the posters at Kidney Week, I have a question about the different trends in hemoglobin in the dialysis patients, and generally it looks like in the Japan study hemoglobin and roxadustat and ESA-Controlled group is relatively close throughout the study.
However, in the China study, there's a wider gap of around 1.5 grams, especially in the early part of the study.
So could you describe what caused differences between the two studies and which would you expect the U.S./EU program to be closer to?
So Peony go ahead and address those issue.
Joel, that's a very good question. The China study and the Japan study are very similar in study design. In both studies patients who were previously treated with EPO were randomized into receiving either roxadustat or ESA. In Japan there is a very small difference, but a very important difference, which I shall highlight and that explains why we see this difference in hemoglobin comparison. In the Japan study, patients who are highly responsive to EPO, in other words, they were on stable doses of ESA prior to randomization and they're achieved hemoglobin were already between 10 to 12 were randomized.
However, in the China study, we took in patients with baseline hemoglobin between 9 to 12.
So there lies the difference of thus having more hyper responders and patients with elevated CRP in the China study. And that is the subpopulation where our drug is seen as a superior to EPO in the China study.
In Japan, you have double product study patients very stable.
That is a source of randomization.
And the range is very narrow as to what you're treating to with comparison to [indiscernible] whereas in China, you have a much broader range of patients. Inflammation is affected. It's allowed to vary across the natural population, whereas in Japan it's restricted in the enrollment, yes.
Tom, that is correct. In Japan, 38% of the patients on dialysis have achieved hemoglobin below 10. But for the purpose of this study, the most enriched population was selected and thought in the U.S./EU program, the entry criteria is, more closer to the China study criteria in the conversion study. And furthermore, as you mentioned in terms, a part of the script that we have over a thousand patients in an incident dialysis study where a baseline hemoglobin is even lower. We did not set a bottom.
So we expect to be able to have enough patients who are inclined for us to make such comparison.
Great, thanks for the helpful response.
Okay, thank you. Michael?
Mr. Yee, your line is open. Please proceed.
Thanks. Good afternoon everyone. Hey, Tom, two questions. Thanks for the information. Two questions, one is, AstraZeneca.
You said this morning, overall that they expect to give obviously an update by the end of the quarter. But I think suggested along with some non-MI or just overall pooled safety data. Maybe you can appreciate that the street does want to know about overall safety, when you report out some of this data.
So what can you say as to what you'll be able to report or at least comfort the street on as regards to pooled safety overall when you report on in December? And the second question is related to a question that Peony just emphasized it relating to hyper responders. Do you believe that you'll have enough patients in the dialysis hyper responder pool that you'd be able to make a significant claims as to either MACE or other cardiac benefits in that population? And how important is that either to labeling or being out of the bundle? All of those types of things, how important is that? What could you see there? Thanks.
Okay. Peony, do you want to try to take on the pooled safety first? We'll come back to the hyper responder after?
Sure, Tom. Mike, yes, we agree that the pool safety analysis is very important. And in December, we are expecting to report out the results from the individual's study data.
However, it's only after individual study have been - the data has been locked and that data becomes available for pooling and before we can provide the pool analysis, so it will be the pool safety data will be provided as a second step.
Yes, I think…?
I think are upon as AstraZeneca and Astellas had given the similar message recently.
So when you report out the individual studies, where you be able to at least make comments either individually or overall tell the street that you feel very good on safety overall, whether individually or not?
So in the case of Astellas, we have completed a couple of studies and they have stated the efficacy readout and then a generalized statement about safety.
That's been their approach AstraZeneca and FibroGen our meeting later this month, formulate how we might want to do this. And I don't know to what degree it might vary from what Astellas is doing. We do not want to provide a forum that could considerably create bias for adjudicators that are working on data.
And so we will be very cautious about the timing when unblinding this happened to make sure that we were at a point with the adjudication where there's no biasing the can be asserted.
And so is a factor, in addition, because the MACE itself was blinded exercise, anything that causes any understanding of retail, we would probably, just for the safe of conservatism, we'll probably wait till the Mason blinding to report. That we be some other things open to talk about but as I said, we have not made decisions yet on that front.
So I hope that…
And more you say probably the better, even if it's not about MACE, obviously.
Oh! Sure, it's attention of various factors and we're studying at very closely. The hypo response idea and questions a very well thought out.
So I would offer that we do expect that there's going to be a portion of the U.S. population that has the characteristics of hypo response, which is to say ordinarily due to inflammation, it would be using much more and much more EPO and much more iron to achieve any incremental change in hemoglobin. There has been an effort to in the incident population accruals in the U.S. to include patients of that type.
Our audience for that work is really with CMS, so they're not going to be concerned about, the statistical readouts, whether or not we have adequate powering, they're much more in the zone of do you have this mechanism around hip side and inflammation. Do you have incremental capability with the medicine that enables us to treat what they consider is about 30% of the hemodialysis population that in their eyes does not have adequate standard of care with current therapies.
And so the conversation is more along the lines of CMS encouraging us to continue on the path of working on a hypo response based on the data from Phase III. To me that's the core of what matters in terms of what's coming out of the Phase III. There is a team working on this CMS and they are aware of the study design and so on, so my comments sort of take that all into account.
That's helpful. Thank you.
Thank you, Michael.
Next question comes from Andy with William Blair. Please proceed.
Thanks for taking my question and congratulations on all the progress this quarter. My question has to do with a policy move. It seems like in the dialysis space, we're kind of moving towards integrated care.
Just wondering, Tom, what's your view on that and how does that impact your original strategy in terms of moving roxadustat out of the bundle as a differentiator?
So I mean, this is a very dynamic situation and it's going to be - some people have to watch very closely.
Let me start with the principal we used in our trial design. With CMS, we have briefed the ability of roxadustat to regulate upside into downregulated in conditions of inflammation which allowed creating red blood cells. And the notion of that is that it allows CMS to make a decision that this is new technology which gets into a zone where they can talk about separate reimbursement if the data justifies that conversation.
And so that dialogue has been going on a path that's not really in the public domain right now, but we expect sometime next year that there'll be some decision making by CMS in relation to that type of concept as it relates to our program.
In addition, we know that both of the companies that are large dialysis organizations or LDOs, those being presenting us in DaVita are encountering increasingly environment where many of their sites cannot achieve cash flow positive results.
And so it's causing a great deal of thinking and rethinking about how to define the populations differently. And both companies are clearly experimenting with in effect offering insurance prior to dialysis for patients there are to treat CKD, so that they can get the patients onboard much earlier.
And so to me that's a real important arena to monitor as time goes on here. And I know that with the people that we are in contact within these organizations, there is a really high degree of demand to understand our data because they are seeing that it is potentially a fulcrum where there's leveragability into a strategy.
And so we've been duty bound and promise to be able to share data as soon as we can.
So I think that it's a really interesting time as to the bundle and what happens with the bundle. It's in my eyes it's certainly an issue with EPO and EPO knockoffs or biosimilar EPOs or whatever people are talking about. But I also think that in our circumstance there was this encouragement from the outset that because you're a different mechanism, CMS has the capability, if warranted by data to address the beneficiaries that do not have adequate standard of care under current therapy.
And so the prism through which they do that evaluation starts with decision that there's a portion of the patients that don't have adequate care and then goes on to evaluate what we have.
And so how that fits into the larger CMS agenda is still not easy to see because there's a lot of things that are being considered by CMS as they sort of reinvigorate the regulatory framework after several years of sort of post-bundle.
Just sort of everybody being very exhausted by what caused all the things that led to the bundle, we saw a big change in viewpoint a couple of years ago. I don't know if that's any help, but that's what we see.
Great. Thanks for the commentary. Thanks, Tom.
There are no final questions in the queue, sir.
So I'll turn the call back over to Mr. Neff.
To everyone on the call, thank you very much for joining today.
We are preparing in the U.S. and China for transformational clinical and regulatory events with our partners for roxadustat.
We have two new drug applications on file in China and Japan and hope to have a third on the U.S. in 2019. In fibrotic disease, Pamrevlumab is continuing to show great potential in treating conditions where there are limited to no options for patients, a high degree of unmet need. And we are very excited to be able to move into Phase III trials in IPF and Pancreatic Cancer and I look forward to sharing DMD too. It was very much excitement about that as well. I would like to thank all FibroGen team members for what we achieve every single day in these programs. This year has been a torrid pace. Lots of people have been working right up at the limit. We really appreciate across the Board the efforts made in our Company. We were all focused on trying to develop these new technologies as medicines, and have the ability to improve lives for patients, who face in many cases very bleak circumstances.
In addition, I'd like to express my gratitude to our partners, AstraZeneca and Astellas, or their ongoing support and assistance and motivation, and incentivization and so on. There's many, many different aspects and for really high quality people we work with. And likewise with our investor community, I am a most privileged to be able to work on these projects in my life. And this happens because investors support them and we endeavor to be as transparent and clear as possible in our reporting, which is going very fast right now.
So we are doing our best to get us updated as fast as we can. There's a lot of data coming. We look forward to keeping everyone updated on our progress. I would like to wish everyone a good afternoon and a good Thanksgiving holiday coming up. Thank you all for being here.
Thank you. Ladies and gentlemen, this concludes today's teleconference. Thank you for participating.
You may now disconnect.