ICPT - Intercept Pharmaceuticals Inc. (ICPT) Q3 2022 Earnings Call Transcript
Intercept Pharmaceuticals, Inc. (ICPT)
Q3 2022 Earnings Conference Call
November 01, 2022, 08:30 ET
Company Participants
Nareg Sagherian - Executive Director, Global IR
Jerome Durso - President, CEO & Director
Linda Richardson - EVP & Chief Commercial Officer
Michelle Berrey - President, Research & Development and Chief Medical Officer
Andrew Saik - CFO
Conference Call Participants
Yasmeen Rahimi - Piper Sandler & Co.
Ritu Baral - Cowen
Steven Seedhouse - Raymond James & Associates
Michael Yee - Jefferies
Antonio Arce - H.C. Wainwright & Co.
Mayank Mamtani - B. Riley Securities
Thomas Smith - SVB Securities
Eliana Merle - UBS
Luke Herrmann - Robert W. Baird & Co.
Catherine Okoukoni - JMP Securities
Presentation
Operator
Good day, and thank you for standing by. Welcome to the Q3 2022 Intercept Pharmaceuticals Earnings Call. [Operator Instructions].
I would now like to hand the conference over to your speaker today, Nareg Sagherian, Executive Director, Investor Relations. Please go ahead.
Nareg Sagherian
Thank you. Good morning, and thank you for joining us on today's call. This morning, we issued a press release announcing our third quarter 2022 results and business updates, which is available on our website at interceptpharma.com.
Before we begin our discussion, I'd like to note that during our call, we will be making forward-looking statements, including statements regarding our approved product and clinical development program, certain regulatory matters, and our strategy, prospects, financial guidance and future commercial and financial performance.
Listeners are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this call, and we undertake no obligation to update such statements, except as required by law.
These forward-looking statements are based on estimates and assumptions that, although believed to be reasonable, are inherently uncertain and subject to a number of risks and uncertainties.
Some, but not necessarily all, of the risk factors that could cause our actual results to differ materially from our historical results or those anticipated or predicted by our forward-looking statements are discussed in this morning's press release and in our periodic public filings with the SEC.
Today's call will begin with prepared remarks from our President and CEO, Jerry Durso; our Chief Commercial Officer, Linda Richardson; President of Research and Development and Chief Medical Officer, Dr. Michelle Berrey; and Chief Financial Officer, Andrew Saik. We will then open the call to take questions.
Let me now turn the call over to our CEO, Jerry Durso.
Jerome Durso
Thanks, Nareg, and good morning, everyone. Thank you for joining us on our third quarter conference call.
I'm pleased with our performance and the significant progress we made in our business this quarter. Specifically, we accelerated end market demand for Ocaliva and PBC, resulting in a return to double-digit net sales growth for the third quarter.
We delivered positive Phase III results for REGENERATE, and continue to move towards our NDA resubmission of OCA in liver fibrosis due to NASH. And we strengthened our financial position, resulting in an overall improved capital structure.
Let me first start with our Ocaliva performance in PBC. We're pleased to have delivered a very strong quarter of double-digit sales growth. The $77.6 million in U.S. Ocaliva net sales reported this morning, represents more than 16% growth over the prior year quarter.
We're encouraged by the accelerated growth we saw in Ocaliva sales this quarter as well as strong growth in new patient starts. And as a result, have increased Ocaliva non-GAAP adjusted net sales guidance to $340 million to $350 million for the year. Linda will provide more detail about Ocaliva's performance in the third quarter shortly.
Turning now to NASH. We remain on track to resubmit our NDA for OCA in liver fibrosis due to NASH by the end of this year based on our Positive 3 REGENERATE study. Given the analysis we've conducted on REGENERATE to date, we believe in the improved benefit-risk profile of OCA, and its potential role as the first therapy for liver fibrosis due to NASH.
In addition to our regulatory activities, our team is focused on refining our commercial strategy and ensuring readiness, while taking a milestone-based approach to our launch investments.
Lastly, as a result of recent strategic financial moves, we've increased our total cash position to approximately $500 million, lowered principal debt outstanding to $336 million and our net cash positive for the first time since 2019. We now have greater financial flexibility to propel our business forward, focusing on growing Ocaliva and PBC, progressing our fibrosis due to NASH program, and advancing our pipeline.
In summary, we remain confident in our ability to drive growth of Ocaliva and increase market penetration, and we maintain a positive long-term outlook for our PBC business.
As the team will discuss later in the call, the long-term outcomes data and real-world evidence we're generating for Ocaliva and PBC are compelling to both patients and prescribers, and we're focused on reaching these audiences with these important data.
At the same time, we're continuing to advance OCA as a potential treatment for liver fibrosis due to NASH, where there remains a high unmet need. Overall, we're well positioned to drive further growth and success.
I'll now turn the call over to Linda Richardson. Linda?
Linda Richardson
Thanks, and good morning, everyone. As Jerry stated, we are very pleased with our commercial performance this quarter. We reported net sales of $77.6 million in Q3 2022, representing a 16.4% increase compared to the same period last year. We are now back to seeing accelerated double-digit growth and believe that Ocaliva's value to PBC prescribers and patients will continue to generate increased demand.
Let's look at the positive dynamics driving these results: new patients, strong underlying demand and customer engagement and education. In the third quarter, IQVIA reported that our NRx volume was up 37% over the same period last year. This significant increase represents the highest NRx volume we have seen in a single quarter since the start of the COVID-19 pandemic in early 2020.
Demand units increased 10% this quarter versus the same period last year. Patient retention and high refill rates, at approximately 90% are key contributors to the demand unit performance we are seeing. Strong customer engagement and communication of the benefits of Ocaliva remain a key element of our strategy.
Our teams continue to reach prescribers in-person and offices, at dinner meetings and are reengaging at key congresses and professional meetings, including the Gastroenterology and Hepatology Advanced Practice Providers meeting and the American College of Gastroenterology meeting last month.
Patients are an important focus of our business and staying connected with them is a priority. We've introduced a new patient campaign to educate and support those who are taking Ocaliva, and we also attended the recent PBC's Patient Advocacy meeting in October.
Finishing up on our PBC business, we've just launched our new promotional campaign for Ocaliva, pushback on PBC. In testing, doctors felt that it further the idea that there was something more that they could do right now for patients with PBC. We believe that this is just the message we need to convey to help increase market penetration in the sizable segment of appropriate patients who could potentially benefit from the addition of Ocaliva to their PBC regimen. This new campaign will be on display at our booth at the liver meeting later this week.
In a few minutes, Michelle will discuss more of our activities at AASLD, including the positive real-world evidence for Ocaliva in PBC that her team continues to generate.
Turning briefly to NASH. We are actively developing and refining our NASH commercial strategy in anticipation of a potential launch next year. Our NASH disease awareness website, focusing on the importance of addressing advanced fibrosis, is up and running with the NASH Tipping Point campaign, which we will also be using in our exhibit at AASLD.
Recent market research has shown that physicians treating NASH are aware of the need to address fibrosis, and see the potential for OCA to be an important option for patients with advanced fibrosis. It is an exciting time to have the commercial team engaged on these efforts, and we look forward to sharing additional details on future calls.
In closing, we remain confident in our strategy to drive further adoption of Ocaliva among appropriate PBC patients, and we are excited about our potential future in NASH, where the unmet need remains high.
I'll now turn the call over to Dr. Michelle Berrey. Michelle?
Michelle Berrey
Thank you, Linda, and good morning, everyone. In addition to our updates this morning, I want to take a moment to note that we'll be sharing new data on REGENERATE, PBC outcomes and INT-787 at the liver meeting starting later this week.
Looking first at NASH. As Jerry mentioned, our team is working diligently to prepare for resubmission of our NDA for OCA and liver fibrosis due to NASH. As we announced over the summer, the planned interim analysis of the month 18 liver biopsies read using the consensus panel methodology, again, showed a response rate for OCA 25 milligrams that was double that for placebo. A strong dose response in antifibrotic effect and other signals of FXR agonism was also observed for the 2 OCA doses studied.
Fibrosis has been shown to be the strongest predictor of liver-related morbidity and mortality. Therefore, we believe this new analysis reaffirms that OCA can play an important role for people living with fibrosis due to NASH.
Safety considerations raised during the 2019 FDA review have been examined more deeply through analysis of the robust and mature safety database of more than 8,000 patient years, the largest and longest running Phase III trial to date in this space.
The hepatic cardiovascular and renal safety events, the FDA requested have been analyzed by experts in 3 adjudication committees. The cardiovascular events reviewed by the committee set a balanced number of events in each of the 3 treatment groups. Core MACE and the major events associated with it were balanced.
Similarly, the adjudicated renal events were rare and balanced. Hepatic events showed a numerically higher number of adjudicated events for OCA 25 milligrams, generally reflected biochemical changes that are common in patients with advanced fibrosis due to NASH and the effects of FXR agonism, and a vast majority were mild.
Importantly, management of the types of hepatic events observed would be well within the purview of gastroenterologists and other liver experts, our target prescribers. Ultimately, we believe that a larger and longer running database helps to address many of the questions raised in the first review as all observed safety findings are both monitorable and manageable. We look forward to sharing additional details on both efficacy and safety from REGENERATE in a late-breaking oral presentation at the liver meeting.
With our new analysis in hand, it is our view that the benefit risk of OCA 25 milligrams in patients with fibrosis due to NASH is strong. Following the NDA resubmission, which is anticipated by the end of the year, we expect an advisory committee meeting in the spring as part of a 6-month review process.
While the REVERSE Phase III study, evaluating the safety and efficacy of OCA in patients with compensated cirrhosis due to NASH did not meet its histology primary endpoint, we were encouraged that the FibroScan data showed a reduction in liver stiffness of 3 kilopascals, a clinically significant result. In addition, there were no new safety signals for OCA observed in this population of patients.
Further analysis of REVERSE data are ongoing, and we plan to share these data at an upcoming scientific conference. Achieving statistical significance on histology endpoint and compensated cirrhosis due to NASH has proven to be an extremely high bar in clinical trials, underscoring the urgency to intervene in patients with advanced fibrosis before they progress to cirrhosis.
As we've noted previously, our planned NDA resubmission is not impacted by the results of REVERSE. The agency has been very clear that REGENERATE and REVERSE enrolled 2 different patient populations. Nevertheless, should the FDA ask for any safety data from REVERSE, we will be ready to provide it.
Turning to updates in PBC. We remain committed to generating a wealth of real-world evidence to support Ocaliva and PBC. We've made significant progress on these plans this quarter.
First, the leading journal, Gastroenterology, published data that showed improved transplant-free survival observed for patients administered Ocaliva in a clinical trial compared to natural history data from 2 large patient registries.
In this publication, patients treated with Ocaliva had an approximately 70% lower relative risk of death or liver transplant at any time during follow-up compared to the controlled patients from either patient registry. The consistent effect size across the 2 external control cohorts strengthens our confidence in these observations. This study is the first to demonstrate that Ocaliva treatment is associated with improved transplant-free survival, the ultimate goal of therapy in PBC.
Starting later this week, we'll be sharing other real-world and outcomes data for Ocaliva at the liver meeting. We're pleased with the analysis of our Phase IV COBALT study with external control has been accepted as a late-breaking poster presentation. A strong OCA benefit was demonstrated when comparing as-treated OCA subjects from COBALT, with rigorously matched external controls. These data provide evidence that OCA decreases the risk of death, liver transplant and decompensation.
Second, we'll be sharing the detailed results from HEROES U.S., our real-world study that leverages Komodo Health, a U.S. claims database, to compare clinical outcomes in a predefined group of patients with PBC who were treated with Ocaliva, and a comparable group of PBC patients who are eligible, but who were not treated.
As a reminder, top line data from this study were shared earlier this year and, again, showed a statistically significant improvement in event-free survival in patients receiving Ocaliva for PBC. Specifically, individuals of PBC received Ocaliva at a 63% reduction in risk of all-cause death, liver transplant or hospitalization for hepatic decompensation than the control group at any time during follow-up.
The real-world evidence we have accumulated thus far from large data sets in the U.S., U.K. and Europe is compelling and consistent and demonstrates the long-term clinical benefits of Ocaliva and PBC, specifically around transplant-free survival, which we know to be the most important goal for patients.
Ultimately, these data will be included in a regulatory submission to FDA in support of fulfilling our post-marketing requirements for Ocaliva and PBC. In addition to the real-world evidence, we will be including expert adjudication of events from our Phase IV study, COBALT, as requested by FDA, which will bring our anticipated timing for the PBC sNDA submission into 2023.
We remain committed to working closely with PBC patients through our clinical trials, meeting our post-marketing commitments and demonstrating the clinical benefits of long-term therapy with Ocaliva.
Building on our long-standing commitment to PBC, our fixed-dose combination of OCA plus bezafibrate is ongoing, and we continue to enroll patients in our Phase II studies evaluating different doses of the 2 components.
We remain excited about the potential benefits that this combination can provide to individuals living with PBC and look forward to sharing updates on the dose selection and on our Phase III study design next year.
Turning now to our earlier stage pipeline. Our comprehensive Phase I study for our next-generation FXR agonist, INT-787, has progressed to its final cohort. We look forward to sharing data from our Phase I study at the liver meeting as well as our lead indication and updates on our proof-of-concept study, FRESH, next week.
At this point, I'll turn the call over to Andrew for our financial update. Andrew?
Andrew Saik
Thank you, Michelle, and good morning, everyone. I will be providing an update of our financial results, and I ask that you please refer to our press release issued earlier today for a summary of our financial results for the third quarter ended September 30, 2022.
As a reminder, the divestiture of our international business was completed on July 1. And as previously stated, our full year results and guidance will include the divested business for only the first half of the year given the date of the deal closure.
Additionally, the sale of the international business and the repurchase of $389 million of our 2026 secured convertible notes netted in a material gain to our P&L, which I will detail later in my remarks.
Let me start with revenue. We had a strong third quarter, recording $77.6 million in net sales as compared to $66.6 million in net sales in the prior year quarter. We reported $87.7 million in total operating expenses and $82.7 million in non-GAAP adjusted operating expenses. This compares to the third quarter ended on September 30, 2022, where we recorded $86.2 million in total operating expenses and $89.6 million in non-GAAP adjusted operating expenses.
Cost of sales were $0.4 million and $0.2 million, respectively, for quarters ended September 30, 2022, and 2021 consisted primarily -- and consisted primarily of packaging, labeling materials and other related expenses.
Selling, general and administrative expenses were $43.3 million in the third quarter of 2022, up from $41.3 million in the prior year quarter. The increase was primarily driven by increased commercial activities and costs related to our patent defense.
Research and development expenses were $44 million in the third quarter of 2022, materially unchanged from $44.7 million in the prior year quarter. Interest expense in the quarters ended September 30, 2022, and 2021 was $5.2 million and $14.1 million, respectively.
For the quarter ended September 30, 2022, interest expense is related to the principal amounts of our outstanding convertible notes and no longer includes any accretion of debt discounts upon adoption of ASU 2020-06.
We reported net income of $267.5 million, an increase compared to a net loss of $3.6 million in the third quarter 2021. The increase was driven by the significant gain resulting from the sale of our ex U.S. business of $371.5 million, which was partially offset by a loss on extinguishment of 2026 convertible secured notes of $91.8 million.
The third quarter of 2022 was a transformative one for Intercept with regard to our capital structure. During the quarter, we successfully repurchased $389 million of our 2026 secured convertible notes. As a result of these transactions, we have reduced our debt by 54%, and reduced our cash interest expense by 58% or $13.6 million annually.
Further, with approximately $500 million in cash, cash equivalents, restricted cash and investment debt securities available for sale and $336 million in debt, we are now net cash positive for the first time since 2019.
In summary, we have a strong financial position and are comfortable that our current balance sheet gives us financial flexibility to grow our existing business in PBC, support a launch in NASH and progress our pipeline.
With that, I'd now like to turn it over to the operator for any questions. Operator?
Question-and-Answer Session
Operator
[Operator Instructions]. And our first question comes from the line of Yasmeen Rahimi with Piper Sandler.
Yasmeen Rahimi
I just wanted a clarification question. Did you comment on that at this upcoming liver meeting, we will be seeing Month 48 biopsy data from the REGENERATE analysis? And if you could just provide some commentary of whether we will be getting both like one point improvement of fibrosis as well as NASH resolution? If you could just provide that, that would be helpful.
Jerome Durso
Michelle, maybe you start there?
Michelle Berrey
Yes. We will not be giving any month 48 data. This submission is focused on the planned interim analysis of the month 18 data. So that will be our presentation, and we'll stop at the month 18. Again, on the resubmission, we focused on the new analysis of the consensus methodology, with being just at month 18.
Yasmeen Rahimi
Okay. But the resubmission will only include week 18, not week 48 either then. Is that correct?
Michelle Berrey
It's focused on the month 18, the resubmission looking at the old central analysis and the new consensus methodology.
Yasmeen Rahimi
Great. And then, can you -- another one follow-up question is in regards to the supplementary data that's being submitted for full approval in PBC.
So what has been some of the communication that you've gotten from the FDA? How receptive are they towards reviewing this data and potentially allowing full approval? Just -- if you could just provide some color beyond what you had in your prepared remarks would be very helpful. And then, I'll jump back into the queue.
Jerome Durso
Yes. Thanks, Yas. Maybe I'll start, and then Michelle can add in. So as Michelle outlined in her prepared remarks, it's a comprehensive package that's being prepared. She outlined obviously the data coming from COBALT as well as a slew of real-world data sets that we think put us in a solid position overall in terms of the comprehensive nature of the package.
We also believe, of course, that Ocaliva continues to be an important medicine and the only second-line therapy in PBC approved. We're continuing to do the right work. We look forward to continuing what I think I would frame has been a productive dialogue with the agency and reengaging with them once we resubmit in defining the work we need to do moving forward. So Michelle, anything else from your end?
Michelle Berrey
The only thing I'd add is we have had a very good interaction with the folks at FDA, including the individuals within the real-world evidence part of the FDA. So we are excited about being -- what would be the first non-ultrarare disease to submit a substantial package of real-world evidence data that we've been generating on.
The standards for the real-world evidence generation have to meet those of a randomized, prospectively enrolled clinical trial. So we've been making sure we've reviewed every one of the guidance's that have been issued over the last 18 months or so by the FDA to make sure that we're meeting those criteria. But we are excited about this opportunity, given the breadth of data that we know we have, given the 30,000 patient years of data that exists for Ocaliva.
Operator
Your next question comes from the line of Ritu Baral with Cowen.
Ritu Baral
I've got one high-level question, a little granular one as a follow-up. Jerry, now that you've got this healthy balance sheet and you're looking towards expenses for NASH launch and potential BD. How are you looking to, I guess, balance the costs of both of them? And if you could give us an update on what you might be thinking about the pipeline on -- just beyond 787 and the bezafibrate combo?
Jerome Durso
Okay. A few items there. I'll try to step 3. Ritu, thank you very much for the questions. I think we do, as you said, feel good about the work we've done on the balance sheet. We think it puts us in a good position as we do all the right work now to finalize and resubmit by the end of the year.
Linda mentioned in her prepared remarks, the fact that the commercial efforts are flexing up. Primarily first, I think in the areas of refining our strategy, taking a contemporary look back into the customer considerations from the payer, physician and payer side. And I think you'll hear more as we get into next year about where we're evolving the commercial thinking.
We are going to, I think, take a prudent approach in how we ramp up towards commercial readiness. And so we'll balance both sides of that. We are excited about the first moves we made in our pipeline with 787, and I'll highlight the fact that we'll have more information about 787 and what we're -- some of the initial data, but also what we're thinking in terms of lead indication as we get into next week.
So those are the first bets from the pipeline. We'll have more to say about the pipeline over time. And again, I think we feel that the moves we made on the finance side give us the means to do what we need to do, both moving NASH forward, continuing to grow PBC and now getting more constructive with the pipeline.
Ritu Baral
So no focus on BD right now in the near-term future to build out the pipeline further than what you decide?
Jerome Durso
So look, I think we're always looking and considering how best to leverage the capabilities we have and the capabilities both on the R&D side and on the commercial side of the house, but nothing else definitive for me to say right now on that.
Ritu Baral
Got it. And just a quick follow-up, Michelle, for you. On the presentation, on the -- I guess, the REGENERATE presentation, you mentioned there'll be more detail on the safety. Can you give us more, I guess, top line on the balance of the SAEs on the hepatic side? You did mention there were more 25-milligram -- sorry, events on the 25-milligram. Can you talk to the SAE number between the arms and the cholestatic events as well?
Michelle Berrey
Yes. Thanks, Ritu. So just before we leave the pipeline, I just want to mention that we are spending a lot of time and resource on our fixed-dose combination and on 787. So really excited to be talking more about that at the liver meeting. So I look forward to sharing that.
On the presentation, as a late breaker, we do look forward to sharing more data. I think you'll be pleased to see the detail we've been able to include in the hepatic events and specifically on those adjudicated by the committee. Most of those that were seen in the placebo group are obviously most related to the progression of disease.
And those that you see in OCA 10 and especially in OCA 25 are really biochemical excursions that are seen. I think what we have been able to show, and we'll be sharing in the presentation, is very reassuring about the overall profile and all very monitorable, manageable and reversible. So again, that's really key when you start looking at some of these hepatic events. That's the detail that we'll be able to share next week.
Ritu Baral
Got it. And one quick last question. As you think about the sNDA for PBC, is there a potential for the sNDA process to validate alk phos as a full approvable endpoint for PBC, thereby potentially expediting the combination pathway?
Michelle Berrey
That's a great question, and one that we've spent a lot of time thinking about. What's very clear about alk phos is -- ALP is really helpful in the early disease stage. But like the aminotransferase's, this tends to burn out as patients have more advanced disease.
And what we are seeing is that total bili is more important, it's a stronger predictor of those outcomes. Now that we have outcomes data, we're really in a great place to be able to look at, develop a multiple -- a composite endpoint that really pulls in multiple different bio measures for these patients beyond ALP.
There's a lot more to the disease than ALP. It was a great biomarker for us for the POISE study in an early disease patient population. But really, as we look at the range -- the broad range of patients who are benefiting from Ocaliva, I think we have a bigger opportunity there to look at now with our outcomes data, and what is the best predictor of those outcomes.
But again, the outcomes data is really what's going to be critical for Ocaliva. The only compound that's now shown the improved transplant-free survival. That's really what's key.
Operator
Your next question comes from the line of Steven Seedhouse with Raymond James.
Steven Seedhouse
It sounded perhaps like the refill rate or the persistence in PBC has gone up recently. I was hoping you could maybe expand on that. And if it has improved of late, what you attribute that to, and if you expect that to persist going forward?
Jerome Durso
Thanks, Steve. We do feel good about the dynamics we're seeing, and Linda can go deeper there.
Linda Richardson
Yes, I think it's really remarkable that you see the refill rate and persistency kind of continuing to climb at this point in a product's life cycle. And we're very keen on that element of our sustainability.
I think some of it comes from clearly understanding how to manage pruritus. That's one thing that we know the physicians understand how to do. And there's also the building body of evidence, where you see what we're reporting with outcomes, and that is extremely meaningful when that is articulated physicians and nurse practitioners, PAs, spend a lot of time with the patients when they're putting on therapy.
And as they have become aware, through the scientific landscape of what we've demonstrated, I think that gives a meaningful push to stay on therapy when some of the physicians who've seen this data presented, seeing the articles have engaged with us even as recently as ACG.
Steven Seedhouse
Can I just follow-up on the pruritus management. Are you noticing -- I mean, are you referring to sort of just treatment regimens that in the real world, providers are optimizing or just getting more experience, is that landscape evolving?
Linda Richardson
Yes, I think there's 2 elements there. There is the reality that the constant reminders and overstatement in checking, "Did you itch? Did you itch? Did you itch?" Do you have any sense of itching in the clinical trial results are different than that, that we've seen in the real world?
And the majority of the pruritus that you see can start in the beginning, and then ameliorate over time, there are activities and things that people can do to help with that. And I think, in the real world, we just don't see it as much, and there was an article on this that was published before on how it is not as extreme as it's made out to be.
So I think you couldn't stay on a therapy that you didn't tolerate, right? And we found that this consistent refill rate is evidence of patient satisfaction and ability to stay on the drug.
Operator
Your next question comes from the line of Thomas Smith with SVB Securities.
Thomas Smith
Just on the OCA resubmission in NASH, you've previously talked about having an additional 500 18-month biopsies available from REGENERATE. Are you expecting the resubmission will include this additional data set? And then can we expect to see these results included in the AASLD late-breaking presentation?
Michelle Berrey
Can we take that, Jerry? Yes.
Jerome Durso
Sure.
Michelle Berrey
Yes. So we will be including those patients who underwent biopsy. These are certainly going to be part of our submission, and we will be including that. What I can say about it is, it's very consistent with what we have seen in the original ITT population that includes just the F2s, F3s.
But because we have on this an additional 750 or so patients who underwent month 18 biopsies, we will include that in our submission. It's not the primary focus of the FDA. They really wanted to look at those for whom we had a central read and this new consensus read to compare those. But we will be, of course, including all of those data.
Thomas Smith
Okay. Understood. And fair to say that this won't be a focus of the late-breaking presentation next week?
Michelle Berrey
It's not a focus. We are really focused on providing more granular data on the safety and tolerability of these patients. Some of the data that we didn't have at the time of the top line. So we -- again, that will be the focus of the presentation.
There's only 10 minutes. So we will be trying to cream as much as we can to make sure we've answered all the questions that we know came up that we just didn't have the answers yet for the top line, but we will be including those additional patients who had month 18 biopsies.
Thomas Smith
Okay. Great. And then just a quick follow-up. Maybe you can provide a little color. What's the latest projection on when we might see outcomes data from the REGENERATE study?
Jerome Durso
So our current...
Michelle Berrey
That's a great question. Our current guidance about 3 years -- sorry, Jerry. We are going to be looking at that with some of the new data that's been published. So -- we'll be able to give you a little more guidance there later next year.
Jerome Durso
Our current estimate, Thomas, in 2025, although, as Michelle said, we'll work to see if there's a reason to update that once we have the right information in order to be able to model -- remodel.
Operator
Your next question comes from the line of Mayank Mamtani with B. Riley.
Mayank Mamtani
Congrats on a strong quarter. So maybe just a couple of related questions. With the NRx volume increase, are you able to comment if there's a particular PBC patient type that you've previously found less viable? Just wondering if it's about the hepatologist behavior post outcome data? Or is it about patient not being [indiscernible] a cost level that need to be elevated in clinical trials? So I think if you could comment on that.
Jerome Durso
Yes, overall, I think the trends look solid and really a result of the updated plan from Linda and the team. I think we've been really encouraged over the past several quarters as we moved out of the label change that our ability to restimulate the growth of new patients for the appropriate patients within the existing label.
And really, I think I would highlight the -- a lot of the efforts, not only with the -- you mentioned the hepatologists but really with the additional allied professionals that are supporting the community-based gastroenterology practices. I think there's been good traction there once we are able to get the message out about the label change.
And as we kind of estimated and forecasted at the time, it would take a few quarters to work through. And I think we're right now in that window where we've worked through that history and you start to see the growth overall accelerating in terms of total demand, but in particularly this new patient start, which I think speaks well about what we should see in the coming quarters.
Michelle Berrey
Yes. And I think this was, in our minds, a predictable even a pivot point where we would start to see the underlying growth. You're no longer talking about label change patients who were dropping out and being compared to a larger database. But we see folks understanding the impact, there is considerable opportunity within the on-label population, the new label population.
And as we continue to use our strategy and talk to gastroenterologists and their supporters in the community, that's where we're getting the message out. And we have not really been able to, other than folks who have requested data from MSLs, we're seeing the data heard the press releases themselves, heard that information, been able to talk about the outcomes data at all.
Our first opportunity to do anything with it, in terms of a sales rep, is to potentially drop it once it's been peer-reviewed and published. And there are ways that you can start to do that, that we'll obviously conform to and follow. But this is just word of mouth and people understanding and programs and questions. So we believe that the growth is still there, and we will continue to move forward with that.
Mayank Mamtani
Great. And then just to clarify, Michelle, your comment on the 2 pieces of the hepatic safety that you're following. One is the -- obviously, the hepatic events that you will have more data next week on the late breaker, but then also the liver outcomes that you're following as part of the efficacy analysis. Could you just clarify -- and maybe this is a silly question, but just to clarify how those do have any overlap, if any? And then I just have a quick follow-up.
Michelle Berrey
So to be clear, they don't have overlap. Although many might be the same events, they're adjudicated through different experts. So we have a hepatic safety adjudication committee that is specifically looking at drug-induced liver injury. So that's the focus of the safety events.
To be clear, in our presentation next week, we will not have any outcomes. The focus of this analysis, which was a preplanned analysis, in collaboration with the FDA, was a reanalysis of the original 931 patients that were read originally under a central read, now read under a consensus panel. We will be sharing those data, plus the additional patients who will be submitted together with the 931 patients.
As Jerry said earlier, we expect that outcomes would be in the 2025 range. We have not started looking at those data with the new modeling that's been available over the last couple of years. That's something that we'll be turning to after the NDA resubmission by the end of the year.
Mayank Mamtani
And just finally for Jerry or Andy, about the IP settlement recently. Could you just talk about the implications and how might you be tracking with other ANDA filers? And if you should hear anything from you in the near-term here?
Andrew Saik
Yes. No, thanks for the question. So really no change there. We obviously have the ANDA filers. We currently have 6 ANDA fliers, 5 of which are included in the current litigation. We continue to maintain that we feel very strongly about our IP, and our current view is that we're going to continue to have IP protection of Ocaliva into the 2030s. So we're continuing to defend our IP. We feel very good about it and really no change, steady as she goes.
Operator
Your next question comes from the line of Brian Skorney with Baird.
Luke Herrmann
This is Luke Herrmann on for Brian. Just a follow-up on 787. Can you remind us how it's differentiated from OCA from what you've seen preclinically? And what we could see in the Phase I data that could provide confidence in this differentiation?
Jerome Durso
Thanks for the question, Luke. And Michelle? Yes, go ahead, Michelle.
Michelle Berrey
Sorry. We have two posters on the abstracts are out now. So one is the preclinical data that I think will be helpful in understanding the differentiation, 787 is a more hydrophilic compound. So that means that the FXR targeting is more likely to be gut -- so more gut, less liver, and that gives us some other opportunities. You'll see that in the abstract and in the poster where we go into some of the preclinical data, including some animal models.
And then we also have our Phase I data. As we mentioned in the comments, we're in our last cohort of the multiple ascending dose study really just to make sure we've got broad coverage there for the exposures depending on which patient populations and their hepatic impairment to make sure we've got that safety.
So we're really excited about this molecule, have a lot -- a breadth of opportunities to explore there, but excited about our lead indication and sharing those data with you over the next week.
Luke Herrmann
Great. And could you share any color about expectations for the time line on getting Phase 2 up and running?
Linda Richardson
We will be sharing those data next week -- early next week.
Jerome Durso
Thanks, Luke.
Michelle Berrey
Thank you.
Operator
Your next question comes from the line of Michael Yee with Jefferies.
Michael Yee
I'm tempted to ask five questions like everybody, but I'm just going to keep it to two. First question is, Michelle, will you have any information on endpoints like progression to cirrhosis or any of the components of the outcomes? Have you looked at any of those individually, and have you -- has the DSMC looked at either an interim or futility on the total outcomes? That's question number one, maybe that 1.5 questions.
And the second question is, it's been a few years, actually since we went back and did the NASH day and all those types of things if we go back. And so there used to be a question about biopsies and how to think about that. How is your thinking around the evolution of biopsy or what payers would use to define FQ3 and biopsies in that type of requirements evolved over the past year or 2?
Jerome Durso
Yes, Mike, maybe I'll jump on the first, and then Michelle can come back a second on the point of -- so obviously, Mike, as we talked about in the past, that is an area of the identification of the right patients in the real world will be an important dimension of a potential launch here. We're -- doing the updated work on where is the market today, the consideration of payers and specialists.
And I would anticipate similarly to what we did, which I guess was about the end of '19, where we had kind of a fulsome look at those elements in advance of launch. We will do that again. I think that some of the work in considerations that we're working through now with our updated data set in hand. So more to come on kind of the commercial thing.
I would just say, and I'm sure we can go deeper on this point, the -- and then we'll see some additional indicators also at the liver meeting next week. The utilization and proliferations of noninvasive means of identification of patients has only grown over the last couple of years. And so there has been some positive progress made on that front that I think is going to be, again, an interesting element in the update that we'll come back with. I think your first question, Mike, was on outcomes, and Michelle can touch on that?
Michael Yee
Yes. Particularly, Michelle, as it relates to either interim utilities or what the DMC is also looking at?
Michelle Berrey
Yes. So happy to touch on that. And as I said earlier, this submission is really focused on the this planned interim analysis and the reanalysis of those 931 patients. Because of that and because it was a planned interim and a reanalysis of those 931, we don't take any alpha hit. And that was really important in our conversations with the FDA that we are not looking at the outcomes. It's really critical.
We don't want to use any of that alpha spend. We want to maintain that and keep that for our outcome data. So we have not started looking at that. The DMC is really focused on safety. We are going to be, as I said, looking at the contribution of histology and progression to cirrhosis. That's a different committee. So not the dili experts, this is a group of hepatologists whose expertise is really in defining that progression to cirrhosis.
So they'll be -- they've been looking at that. They report into the DMC, there -- all of our committees are blinded as are the 3 safety committees. This progression to cirrhosis outcomes committee also remains blinded, and then they feed that into the DMC.
Just to be clear, though, because of DMC is just looking at safety, it doesn't mean that they don't also look at efficacy and those rates, I've been involved with other DMCs where you don't have any chance of showing an outcome. And in that instance, everything that's on the safety front is a risk. Therefore, there is no benefit risk.
So that's always part of a DMC charter and kind of what underlies the DMCs role. So again, a different committee that's looking at those. We will be looking at that and providing them with some additional data next year and doing some additional modeling.
I just want to touch again on the noninvasive tests. We know that you can't validate a noninvasive surrogate marker against another surrogate marker. FDA has been pretty clear about that. It's -- they can only be validated against outcomes. So we know collecting these data throughout this very large trial that we now have patients out at 6 and 7 years. So we do have that opportunity coming around the corner for looking at outcomes.
And that is going to be really critical for the validation of some of these noninvasive tests. It's a few years away, as Jerry said, though, not something that's going to be validated prior to our -- or what could potentially be a first approval, which is just, again, based on these 18-month biopsies.
Certainly, a hot topic, something we're continuing to pay a lot of attention to, and a mass, a lot of data in these thousands of patients. Thanks for the question, Michael.
Operator
And your next question comes from the line of Ed Arce with H.C.
Antonio Arce
Firstly, I wanted to ask in PBC, given the additional data that you're submitting towards full approval, including COBALT and the real-world data sets, that you mentioned and in particular, the data around transplant-free survival.
I'm just wondering, if there's any expectations that you shared with us in terms of label updates after that review? Either in terms of additional long-term data or removal of any sort of warnings or restrictions? And then I have a follow-up.
Jerome Durso
Michelle, maybe you can jump in there?
Michelle Berrey
Yes. So we're really focused on the review of the real-world evidence, the importance of having these what the FDA considers irreversible morbidities, so survival certainly falls in that category and how that can play a role.
Having said that, this would be the first non-ultrarare condition that this will be reviewed. So I don't really want to speak to our expectations or what we anticipate the FDA would make decisions on that basis.
I think the importance for us is really going to be getting the word out about these outcomes, about improved transplant-free survival and how critical that is, and we've really moved beyond the biochemical markers.
This is not about an accelerated approval anymore. This is really about fulfilling our post-marketing requirements and spreading the word that across multiple different independent data sets, we now have data on transplant-free survival, which I know how critical that is for patients to consider.
Antonio Arce
Okay. And then turning to your pipeline. I think you mentioned earlier a lot of time and resources are spent now on this fixed-dose combination study as well as 787. So just wondering, if -- beyond the data that we can expect this weekend. Wondering, if you could update us on the status of both of those programs, in particular, the timing of the full timing of full data from the current studies?
Michelle Berrey
Yes, the fixed-dose combination probably. Yes, early next year on the fixed-dose combination, we look forward to sharing some of the data on the interim analysis for these 2 Phase II studies that are exploring different doses of OCA and bezafibrate.
We know bezafibrate has been used at some of the higher doses, 100 milligrams in a generic form in Europe. We're looking at whether combinations of the 2 drugs can improve on efficacy, improve tolerability. So a lot of questions that we want to look at. It's not just on the PK/PD though, I really want to look at overall safety tolerability. That's a really important question for us as well as the design of the Phase III study.
So a lot of thinking going on right now, while we're recruiting the -- finishing up the Phase II studies, both in the U.S., Europe and beyond. For the Phase IIs, in addition to a large Phase I study, we mentioned previously that we were backfilling some of the data from Phase I, given it's been a while since bezafibrate was developed.
Some of those studies weren't to the standards that we wanted. We really wanted to explore some of the drug-drug interaction data as well. The 787, as well, we will be sharing some data as early as next week. And then I think you'll be hearing a lot more about that Phase II study in early 2023. So we're excited about the growing pipeline.
Antonio Arce
Great. Thanks for that, and look forward to seeing you in D.C. in a few days.
Operator
Your next question comes from the line of Ellie Merle of UBS.
Eliana Merle
Can grasp on all the progress in PBC. Maybe just in terms of the recent strength and how you're thinking about longer term, when you might sort of face some competition with some new players, such as some other PPARs. Maybe kind of how you're thinking about how bezafibrate might compare to some of these PPARs? And specifically comment on kind of the selectivity across people PPAR alpha/delta?
And also just in terms of what we can look for perhaps in some of the upcoming data sets from your bezafibrate combo and thinking about comparing to some of the other sort of emerging PBC assets?
Jerome Durso
Okay. Maybe we start maybe Michelle from your side, and then Linda, if there's anything in terms of everything we're learning on the competitive front in the market, you can go both ways there.
Michelle Berrey
I think for me, on PBC, again, reiterating the importance of our ability to now show transplant-free survival. I know a lot of our competitors are focused on the earlier phase of developments on the biochemical changes and how that might predict long-term outcomes, but we move past that.
We now have those data from these large real-world studies, including claims, databases, patient registries. And I think that's really what is the main take-home there for -- from a competitor perspective.
We are looking at how we can help clinicians and patients understand what their biochemistries might mean, now that we do have those outcomes data, so look forward to that not focused on ALP there, which we think is really most helpful in those earlier-stage patients and not across the broad spectrum.
So be watching for more data again on the real-world outcomes and some of the ways we might help our patients and clinicians and predicting how the changes that they're seeing might actually correlate with the outcomes that we've seen. Linda?
Linda Richardson
I kind of divide my comments into some categories related. First, to bezafibrate, we know that bezafibrate has been studied for use in the management of PBC, an investigator-initiated trials and in larger trials, particularly in Japan. So there's a familiarity with the effects of that bezafibrate pan-PPAR activity that are well understood.
Now when we combine that, as Michelle was saying, with the known impacts that we have, and there's 2 different mechanisms of action, when we're looking at the fine balance. What's the optimal potential for dosing? Two, actually increased efficacy, potentially improved tolerability. And C, if we can really come up with a new molecule, that will be an NCE with its own patent life, et cetera.
So we look at it from what can this -- I think the probability of success, technical success in lowering and improving biomarkers and PBC is certainly there. We've seen evidence from small studies in Europe with the combination of the 2, showing an improvement after URSO, greater improvement if you add Ocaliva first, and then bezafibrate second, but an improvement regardless of order.
So I think in terms of a commitment to PBC and life cycle management, we certainly have that opportunity. When we look at the competition currently coming out with different PPARs who are, I think, trying to position themselves vis-a-vis one another and creating delta, PPARs and whatever, delta, it's PPAR. So that's kind of the marketing activity and gamesmanship in terms of positioning.
So I understand totally what's going on there. But bilirubin, as Michelle has indicated, bilirubin, what we're seeing is the most predictive element, and we have very strong activity on bilirubin and we've sustained bilirubin with a lower and sustained bilirubin levels in our data or in the POISE open-label extension data, we have that data. We have data not only on bilirubin, but we also have data on stabilization of fibrosis.
And physicians when they've seen this presented as some additional information we've been talking about in our campaign, that is not what one would expect, right? This was prior to even having the results on outcomes. So I think all of this leads to the impressive data we've generated from multiple sources.
I mean if this were a one-off, you'd be pleased, but when you see it triangulating from different databases and coming up with the same kind of literally overlayable reads on the risk reduction, that's an impressive thing to be presenting. So I feel like that data is beyond ALP and is starting to hit the marketplace and moving forward. So -- we'll see how that -- how other people answer to our ability to discuss and generate outcomes data.
Operator
Your next question comes from the line of Catherine Okoukoni with JMP Securities.
Catherine Okoukoni
This is Catherine Okoukoni, coming on, on behalf of Jon Wolleben. And one question that we had was how the emerging market might play into the FDA decision regarding the supplemental package in PBC? I know you've sort of discussed the commercial aspect of it, but doesn't play any role in the FDA decision as it looks through the supplemental package?
Jerome Durso
I'm sorry, I didn't follow the first -- I couldn't hear the first part of your question, Catherine. How -- what plays into the FDA's consideration?
Catherine Okoukoni
The emerging markets, like the emerging pipeline that's coming out in PBC.
Jerome Durso
Yes. Look, I mean, Michelle can shift -- I mean, I would say upfront. I think the FDA is looking at our package. As we said, it's a pretty robust package. We're in a position of advantage in terms of our ability to have a long-term view at the questions on the table.
And so we've been, I think, generating the data accordingly and approaching the conversation with the FDA with a focus on what we've been able to do from a longer-term perspective based on all the experience, as Michelle indicated, the COBALT data set, the real- as well as the post-marketing data with over 20,000 patient years, I think, puts our data set in a unique perspective there.
Linda Richardson
I think to the competitive -- the competitors are not anticipated to be on the market during the time frame where we're being reevaluated and is the only second line therapy approved for PBC patients. I'm not sure that competitive context comes into play with the immediacy of our review next year potentially.
Catherine Okoukoni
And I just had one follow-up as far as timing. Beyond just next year, do you have -- are you able to refine timing at all?
Jerome Durso
No, what I would say is the work is ongoing, obviously, in parallel to the heavy work that Michelle and her team are doing with the NASH resubmission expected by the end of the year. And if we have a need to refine, we'll do that at the appropriate point.
Operator
Your last question comes from the line of Salveen Richter with Goldman Sachs.
Unidentified Analyst
This is Mason on for Salveen. On NASH and the various segments of the patient population, your team has talked about Ocaliva positioning for the more advanced population and focus more on the F3 later-stage population. So with respect to the REVERSE trial results, even though the FDA sees these as distinct indications, do you think that missing the endpoint there has any impact on how clinicians view Ocaliva potential as an antifibrotic in F3 patients, like especially for people who are sort of teetering between F3 and F4, it would just be really useful to understand how your team thinks about this?
Jerome Durso
Yes. Thanks for the question, Mason. We have indicated in the past, and that's part of the validation work that Linda's team has -- is undertaking now a focus more towards the advanced fibrotic segments. I think we're still going towards that direction, albeit we're refining exactly what that may mean with the current data set we have on mind as Michelle indicated, and we've continued to say.
The agency has looked at these populations differently. And it was a different population. The more advanced compensated cirrhotic in reverse is a different population with more advanced disease. And obviously, 25 milligrams for the time studied was not an effective dose and contrast that to what we saw in REGENERATE. We're now multiple times at 25 milligrams, we see the strong antifibrotic effect.
And the understanding in the potential target physicians, gastroenterologists and hepatologists about the role of impacting fibrosis for those more advanced fibrotic's segment is something that is well understood and appreciated. And I think that while we'll refine exactly how we'll position things, I do believe that the antifibrotic effect for the more advanced populations like we studied in REGENERATE will be at the heart of our value proposition as we prepare to launch.
As I said earlier, we'll have a lot more insight on that as we get closer, and we'll have the opportunity to -- and similar to the way we did in the past, present more details on the commercial plan in the future.
Yes, I think that's all the questions we had. I want to thank everybody for joining us today. As I said in the upfront. We feel very good about the progress that we made this quarter. We look forward about the work ahead and particularly interesting sharing an in-person session with the liver community at the meeting next week down in Washington, D.C.
So thanks, and look forward to providing more updates in the time to come. Thanks, and everybody, have a great day.
Operator
This concludes today's conference call. Thank you for your participation. You may now disconnect.
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Intercept Pharmaceuticals, Inc. (ICPT) Q3 2022 Earnings Call Transcript