Travere Therapeutics, Inc. (NASDAQ:TVTX) Q3 2022 Earnings Conference Call October 27, 2022 4:30 PM ET
Company Participants
Naomi Eichenbaum – Vice President, Investor Relations
Eric Dube – President and Chief Executive Officer
Jula Inrig – Chief Medical Officer
Peter Heerma – Chief Commercial Officer
Chris Cline – Chief Financial Officer
William Rote – Senior Vice President of Research and Development
Conference Call Participants
Maurice Raycroft – Jefferies
Greg Harrison – Bank of America
Tim Lugo – William Blair
Liisa Bayko – Evercore ISI
Laura Chico – Wedbush Securities
Ed Arce – H.C. Wainwright & Co.
Operator
Good day and welcome to the Travere Therapeutics Third Quarter 2022 Financial Results and Corporate Update Conference Call. Today’s conference call is being recorded. At this time, I would like to turn the conference call over to the Vice President of Investor Relations, Naomi Eichenbaum. Please go ahead, Naomi.
Naomi Eichenbaum
Thank you, Carrie. Good afternoon, and welcome to Travere Therapeutics third quarter 2022 financial results and corporate update call. Thank you all for joining us.
Today’s call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined for the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer. Dr. Bill Rote, Senior Vice President of Research and Development will join us for the Q&A session.
Before we begin, I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement.
Please see the forward-looking statement disclaimer on the company’s press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, October 27, 2022, and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.
With that, let me now turn the call over to Eric. Eric?
Eric Dube
Thank you, Naomi, and welcome to Travere, and good afternoon, everyone. During the third quarter, we continue to execute toward our vision of being a leader in the global rare disease community. We did this through the continued development of our pipeline with the objective of positioning it for sustainable, diversified growth for years to come. And by strengthening our organization to support broad access to our approved medicines, while being in a position to meet the needs of patients as our potential new therapies become available.
Notably, during the quarter, we continued our efforts to position sparsentan to become the first non-immunosuppressive therapy for IgA nephropathy and FSGS as a potential new treatment standard, if approved. A couple of weeks ago, we provided a regulatory update on our NDA for sparsentan in IgA nephropathy, that is currently under priority review with the FDA for Subpart H accelerated approval.
In that update, we were pleased to report that we have received a draft label on time, and that no advisory committee is expected and no new data or trials have been requested as part of the review process. During our late cycle meeting interaction, the FDA did unexpectedly asked us to incorporate liver monitoring into our planned REMS.
I am pleased to report that we have submitted our proposed updated REMS and we recently received confirmation of the expected 3-month extension of our PDUFA target action date, which is now February 17, 2023. Perhaps most notably, we have been very pleased with the continued enthusiasm for the strength of our clinical data supporting the profile of sparsentan. We have continued to hear this from the nephrology community since the update was provided a couple of weeks ago.
I would also like to highlight that while the submission of a revised REMS has resulted in an extension of our PDUFA target action date, our teams were well prepared and in a strong position to launch this November. This is a great testament to Peter and his teams and to the whole organization as it is no small feat to prepare for the launch of a potential new treatment standard. We will utilize the added time to further enhance our understanding for how we can best support patients and providers in the IgA nephropathy community and be even more prepared for a successful launch.
Outside of the U.S., we were very pleased to have the EMA accept for review the conditional marketing authorization application for sparsentan for the treatment of IgA nephropathy. We look forward to working closely with our partners CSL Vifor throughout the review process, and we expect a review decision on a potential approval in the second half of 2023.
Lastly on sparsentan, we continue to be pleased with the progress of our ongoing pivotal Duplex Study in FSGS. And we look forward to top line data from the 2-year endpoints in the first half of next year. If the data are supportive of an FSGS regulatory submission, and assuming approvals in IgA nephropathy, we would anticipate being in a position to submit an sNDA in the second half of next year, and a subsequent variation to our European CMA application.
Elsewhere in the pipeline, our pegtibatinase program for classical homocystinuria, or HCU continues to advance. Jula will be going into a bit more detail shortly. But we’re pleased with our regulatory interaction during the quarter which enables — enabled us to advance on the path towards utilizing a total homocysteine biomarker as the primary endpoint in a Phase 3 study.
Let me now turn the call over to Jula for the clinical update. Jula?
Jula Inrig
Thank you, Eric, and good afternoon, everyone. We continue to hear regularly that physicians and patients are seeking non-immunosuppressive treatment options to treat their rare kidney disorders. Importantly, sparsentan is the only molecule in development, which blocks two causal pathways in the pathophysiology of kidney disease progression, namely the endothelin and angiotensin pathways.
The relevance of this dual inhibition in a single molecule is that sparsentan has shown the greatest reduction in proteinuria to date for non-immunosuppressive agent in a pivotal study against an active control in IgA nephropathy. If approved, sparsentan would be the first and only non-immunosuppressive treatment approved for IgA nephropathy and we continue to have confidence that it can ultimately become a new treatment standard.
As it relates to our NDA under priority review for sparsentan in IgA nephropathy, we noted in our update — in our update 2 weeks ago, that we were pleased to have received a draft label, and that the overall process appears to be moving well. As Eric highlighted, we did receive an unexpected request for our REMS to include liver monitoring.
I will reiterate that FDA communicated to us that this request is being made in part because serious drug induced liver injury has been associated with other treatment options that intervene in the endothelin pathway, and that the sparsentan database will not be final while being reviewed under the accelerated approval pathway.
Additionally, it was highlighted to us that there was a desire to have education and monitoring as this would be the first time nephrologists would be using a medicine which blocks endothelin. Most importantly, there have been no reported clinical diagnoses of sparsentan related liver injury in the program to date, and or adverse events of interest related to ALT/AST elevations in both of our Phase 3 studies standing nearly 800 participants at the time of the data analyses were comparable between sparsentan and active control irbesartan.
As you heard from Eric, we have submitted our updated REMS proposal back to the FDA. Our goal is to make the REMS effective for liver monitoring and convenient for patients, their physicians and support staff. And there have been a number of examples that we’ve been able to learn from recent weeks. It’s also important to note that many nephrologists and their practices are already familiar with the REMS process.
Additionally, nephrologists routinely order and monitor labs for every patient, so monitoring liver function tests should be seamless with their current clinical practice. We recently received confirmation of the 3-month extension and our new PDUFA target action date of February 17 of next year. We look forward to continuing to work with the FDA through the labeling and review process.
We will use the opportunity provided by the extension to further our IgA nephropathy disease state education for physicians and our work with the supportive patient advocacy groups in the nephrology field. Our FSGS program for sparsentan continues to progress as planned. We believe that we are on a path to an sNDA submission next year, if sparsentan is approved for IgA nephropathy, and the 2-year data in our pivotal Phase 3 DUPLEX study progresses in a favorable manner.
To that end, we are pleased with the continued conduct of both the ongoing DUPLEX and PROTECT studies and we remain on track for the top line readouts from the 2-year endpoints next year. For FSGS, we expect this will be in the first half of 2023 and for IgA nephropathy in the second half of 2023.
Lastly, on sparsentan. ASN Kidney Week is occurring next week. This is an excellent opportunity for us to engage with the nephrology community. We look forward to sharing insights from our growing body of research for sparsentan in both IGA nephropathy and FSGS including our two oral presentations and nine poster presentations.
I’ll now turn to our pegtibatinase program, which continues to advance towards Phase 3 development. I am pleased to report that we believe we have line of sight to completing enrollment in the sixth cohort of our ongoing Phase 1/2 composed study, and that we continue to gather data from patients from the first five cohorts in the open-label extension, all of which will be critical in forming our views for a pivotal study.
We also completed our second official biomarker interaction with the FDA and believe we’re making sound progress towards utilizing total homocysteine as a primary endpoint in a pivotal study. We’ll be utilizing our learnings from this interaction to guide our upcoming multidisciplinary meeting afforded by breakthrough therapy designation to further align on the design of a pivotal study.
In parallel to the clinical and regulatory work, we continue to work through the burden [ph] global supply system to make progress on building supply for the pivotal phase of development and commercial readiness. Overall, I am very pleased with the continued progress of our pipeline and the potential for us to continue to deliver new greatly needed treatment options to the rare disease community.
I’ll now turn the call over to Peter for the commercial update. Peter?
Peter Heerma
Thank you, Jula. During the third quarter, our commercial organization continued to deliver our approved products and build certain momentum towards the potential launch of sparsentan in IgA nephropathy. So the approved products, we have another quarter of solid demand across our commercial portfolio.
For Thiola, we are pleased with the continued performance despite the evolving competitive landscape. As we have talked about throughout the year, we are seeing the impact of generic dynamics affect net sales. And we expect this to materialize further into quarters ahead.
Overall, we remain pleased with how we have continuously identified, treat and supported patients in homocystinuria community. Our bio asset portfolio continues to deliver solid growth in the third quarter. The Goldman [ph] field team has had a long standing dedication to educating pediatric geneticists, as well as hepatologist. And these efforts have been key to [indiscernible] continued success.
Our established commercial footprint allows us to build upon our strengths as we prepare for successful loans of sparsentan in IgA nephropathy, if approved. Over the last 8 years, our commercial organization has built a track record of strong execution in identifying, treating and serving people affected by rare diseases. This has allowed patients timely access to treatment and support for approved indications.
We completed our recruitment efforts to expand our team in preparation for the sparsentan launch in IgA nephropathy and have built a seasoned nephrology sales force. This established sales group has an average of nearly 20 years of specialty experience, mostly within nephrology. The team has completed initial trainings and is gaining familiarity with the communities they expect to serve.
Of note, our team was prepared for a launch of sparsentan in November, if it would have been approved. And as a result, we have great confidence that we will be even better positioned in February. After speaking to patients and nephrologist about new REMS requirements for liver monitoring, we believe that the potential for sparsentan to become a new treatment standard in IgA nephropathy remains unchanged.
As you heard from Jula, the need for non-immunosuppressive treatment options that address the active pathway for people living with progressive IgA nephropathy has never been greater. As a dual endothelial and angiotensin receptor antagonist, sparsentan is the only treatment and development that inhibits two critical pathways in the pathophysiology of the disease.
We believe that is what has contributed to sparsentan demonstrating the ability to reduce proteinuria by nearly 50% in a pivotal Phase 3 study, against an active control. With our results, and the fact that sparsentan would be the first non-immunosuppressive treatment indicators for IgA nephropathy, if approved. We continue to believe there will be an addressable patient population of 30, 000 to 50,000 patients at once in the United States.
Based on what we know today, the initial onboarding and education in the REMS process, and the frequency of monitoring could result in a more gradual uptake than we have originally expected. But we will continue doing additional research to further understand these dynamics. We have already learned quite a bit from studying some of the other programs that have done very well with similar type of REMS.
We believe the key to our success will come in proactive education and providing the support needed to make the process most convenient for physicians, staff and patients. With the added time from the PDUFA extension, our team will be even better position for successful loan for sparsentan for IgA nephropathy, if approved.
Let me now turn the call over to Chris for the financial update. Chris?
Chris Cline
Thank you, Peter. Good afternoon, everyone. I’m pleased with the continued financial strength of our organization. We’re well-positioned to support our ongoing development programs as well as the upcoming potential launches that can meaningfully change our growth trajectory. For the first quarter of 2022, we reported total revenue of $53.5 million, consisting of approximately $50.8 million in net product sales and $2.7 million in collaboration revenue from our European collaboration with CSLB for. This compares to $54.2 million in their product sales and $14.0 million in collaboration revenue reported for the same period in 2021.
Reported a GAAP net loss of $69.7 million for the third quarter of 2022. After adjusting for noncash expenses and income tax, we reported a non-GAAP net loss of $48.9 million for the third quarter of 2022. On a GAAP basis, research and development expenses were $59.3 million for the third quarter of 2022. The increase compared to 2021 is largely attributable to the continued advancement of the sparsentan impact about news programs, including increased headcount as well as medical affairs activities.
On an adjusted basis, R&D expenses were $54 million for the third quarter of 2022. Relevant noncash expenses for the third quarter included $5.3 million of stock-based compensation and amortization. On a GAAP basis, selling, general and administrative expenses for the third quarter of 2022 were $57.5 million. The increase compared to 2021 is largely attributable to launch preparations, including increased headcount and commercial support.
On an adjusted basis, SG&A expenses for the third quarter of 2022 were $45.4 million. Significant noncash adjustments for the quarter consisted of $12.1 million and stock-based compensation and depreciation and amortization. For the balance of 2022, we anticipate a modest increase to operating expenses from our third quarter levels. And we continue to have a strong financial foundation.
We ended the third quarter with $506.3 million in cash and cash equivalents. Importantly, we believe this cash balance can support our operations into 2024. This takes into account the extension of our PDUFA date into the first quarter of next year, the potential for further competitive dynamics for Thiola. Investing in sparsentan monitors for both IgA nephropathy and FSGS, advancing pegtibatinase as well as the milestone payments we expect to pay related to regulatory achievements for sparsentan/pegtibatinase.
I’ll now turn it back over to Eric for his closing comments. Eric.
Eric Dube
Thank you, Chris. With confirmation of our new PDUFA date, and the ongoing CMA review process in Europe, we believe we are well-positioned for sparsentan to become the first non-immunosuppressive treatment approved for IgA nephropathy in the U.S and Europe. With the added time afforded to us by the extension in the U.S., our experienced commercial and medical affairs teams will be working even more diligently to enable sparsentan to become a new treatment standard, if approved.
In parallel, we will look to add to our sustainable growth with the upcoming readout from the DUPLEX study as sparsentan and FSGS in the first half of next year, and the continued advancement of the pegtibatinase program towards a pivotal study in 2023.
Let me now turn the call over to Naomi for Q&A. Naomi?
Question-and-Answer Session
Operator
Thank you. [Operator Instructions] We will take the first question from the line of Maurice Raycroft with Jefferies. Mr. Raycroft your line is open.
Maurice Raycroft
Hi. Thanks for taking my question and congrats on the update. Starting off, wondering if you can talk more about what your proposed REMS plan is. And talk more about the recent examples that you’ve learned from which Jula mentioned. And lastly, do you have evidence that would support less frequent REMS testing such as every three months, if you can talk about that?
Eric Dube
Sure, Maurice. Great question. Thank you for that. Well, I’ll certainly turn it over to Jula to provide a bit of detail on the proposed REMS and what we’ve learned from other REMS, particularly those within the renal space. What I would remind you and everyone is that the REMS that is submitted is still proposed, we do not yet have a final REMS designed and agreed with FDA, nor do we have a final label. But with that in mind, Jula, I’ll turn it over to you to provide a bit more detail on those questions.
Jula Inrig
Yes, thanks, Maury. So we submitted back monitoring that’s consistent with how we monitor it within our Phase 3 studies and as a reminder, we monitored quarterly within our trials. And this was effective, we didn’t identify any cases of concern of liver injury. We do know there’s another number of other analogues less that are within the rare nephrology space with regards to liver monitoring, we know tolvaptan and there’s a cadence of different levels of monitoring that has been done from slightly more frequent monitoring, which then tends to decrease over time.
I will also point out that there’s a number of agents that nephrologists are familiar with that we’re quite aware of like MMS that’s used within the patient population that are familiar with REMS processes and ESAs and then some other in the transplant paste space and importantly that has an impact at the utilization of these agents. And really they’re important for education of the nephrologists their practice and the patience. And ultimately, our goal is to make it convenient and effective.
Operator
[Operator Instructions] And we’ll take our next question from Greg Harrison from Bank of America. Your line is open.
Greg Harrison
Hey, guys. Hey, guys thanks for taking our questions. First one is, do you have a sense on whether the sulfonamide [ph] chemistry has anything to do with FDA’s view of the liver risk for sparsentan?
Eric Dube
So, Greg, thanks for that question. And no, we are not aware of any link that the FDA is looking to make there. We are aware of some misinformation about sparsentan in this regard that was circulating following our regulatory update 2 weeks ago. Now the FDA has not in any time during our review of NDA or in our interactions mentioned anything related to the chemical structure of sulfonamide group being related to the need for liver monitoring or the risk of liver damage. What they did raise, however, really is two important aspects in them making this decision. The first is the need for additional monitoring based on the potential class risk within agents that block endothelin.
And the other is an evolving data set for sparsentan under accelerated approval, and that was really the rationale not based on what has been sort of a hypothesis that arose about 20 years ago with the first approval of an ERA and whether the liver damage risk was associated with the sulfonamide group. What we do know now is that it’s much more multifactorial, but this hypothesis has not really been proven out. Most importantly, there have been no reported clinical diagnoses of sparsentan-related liver injury in the program to date.
Greg Harrison
Okay. That’s helpful. And then one follow-up is do you expect that there will be any similar liver monitoring requirements in ex U.S. geographies? And if so, could there be any change to your timing assumption?
Eric Dube
Sure. So we certainly have looked at what other agents in Europe have for their label as well as potential monitoring, and I’ll ask Bill to cover what we’ve learned thus far.
William Rote
Certainly, Eric. Our marketing application in the EMA was recently accepted for a review. So we haven’t engaged with active discussions with EU reviewers at this point. So we don’t know their perspective on potential monitoring for liver enzyme elevations. If you look at the process in Europe, they don’t really have an analog to REMS. They take a little — a slightly different tack where they focus predominantly on education. So we will be able to assess this in the future as we get more interactions with the EMA.
Greg Harrison
Got it. Thanks for taking the questions.
Eric Dube
Thanks, Greg.
Operator
We will take our next question from the line of Joseph Schwartz from SVB Securities. Please go ahead.
Unidentified Analyst
Great. Hi, all. This is Will on for Joe. Thank you for taking our questions today. Congrats on the continued progress this quarter. So I guess one for us to start with the addition of the liver REMS and the expected black box warning, some may view the perceived risk benefit profile for sparsentan has changed a bit. So have your assumptions of the addressable market also changed? And do you still expect that similar kind of demographic to be addressable at the launch? Thank you.
Eric Dube
Yes, it’s a great question, Will. And I’d say that based on our assumption that has not changed. And I need to caveat this by, we’ve not seen the final label, but based on what we understand and how others have labeled for liver monitoring, we do not believe that our calculations of addressable population that Peter mentioned in his prepared remarks will change. But I’ll ask Peter to comment a little bit more about how he and his team are thinking about the potential opportunity upon approval.
Peter Heerma
So, thank you, Eric and thanks Will for the question. I think it’s important to realize that this is a rapid progressing patient population with limited treatment options. So the unmet need remains high, especially for a product with a non-immunosuppressive profile that has demonstrated to reduce proteinuria which is nearly 50%. As you may have seen over the last few years, research has consistently called out that nephrologist characterized sparsentan as the most desirable product in development. So within that context, if you look at the liver monitoring within the REMS, I think there’s good analogs out there and Jula was talking about it, that have made it convenient for patients and physicians. And these products were successful in their commercial uptake.
So we believe that the profile of sparsentan remains unchanged and has the potential to become foundational treatment for IgA nephropathy patients. REMS may take some additional educational and logistical efforts and that may have some impact on the initial uptake because we are further informing ourselves what it could look like. But most importantly, we have the experience with our hub and patient services infrastructure to provide customized patient solutions that will support the REMS implementation. And it’s also good to realize that many progressing patients [indiscernible] on a quarterly base and quite often even monthly. And [indiscernible] really a point in the script, obtaining labs always is a standard practice to inform these patient visits.
Unidentified Analyst
Great. Thank you. And then if I could just sneak in a quick follow-up here. Looking next year to the early days of the launch, are there any analogs for kind of the gradual uptake you might expect with the liver monitor? And how are you thinking about the overall cadence for the first year? Thank you.
Eric Dube
Yes. Peter, why don’t you take that one?
Peter Heerma
Yes. I think Jula was mentioning [indiscernible]. I think that’s a good analog in rare nephrology. They were launched in 2018, has been successful in their uptake. But I think it’s a good — that’s a good benchmark for us.
Eric Dube
Yes. And I think what’s important is the work that Peter’s team is doing to further refine our assumptions and estimates through market research with a revised target product profile that reflects liver monitoring. So we will be able to provide a bit more detail on that in the future, but I think, as you point out, we’ve been focused on the analogs. And it does suggest that long-term we will be successful or can be successful to launch. But as Peter mentioned, it’s going to take a bit of education upfront, and we want to be cautious just in assuming that, that could lead to slightly more gradual uptake to begin with.
Operator
We will take our next question from the line of Carter Gould with Barclays. Please go ahead, sir.
Unidentified Analyst
This is Justin on for Carter. Thanks for taking the question and congrats on all the progress. Wondering if you can provide sort of a rough estimate around the number of patient years worth of data you have for patients that have been treated with sparsentan. And related to that, if there’s sort of a hurdle with thinking about how substantial this database might need to be to revisit the REMS requirement down the road.
Eric Dube
Yes, Justin, thank you for the question. And Jula, I will turn that over to you.
Jula Inrig
We haven’t publicly released the amount of patient years that we have. What I can say is that we are going to present at ASN upcoming some long-term data that we have from DUET. Realize that this is under accelerated approval. So as we’ve released before, how much data that we have of patients. So under accelerated approval, we don’t have the full data set or analysis. So as we said, we have 800 patients on our clinical trials, half of those are on sparsentan. As we’ve said before, we have about 1,200 patients who’ve been exposed to sparsentan, but some of those were earlier trials where patients got shorter duration of exposure and treatment time period. So some of them may not have mixed both for a longer duration.
So — and to your second point of what is it going to take? That’s going to be a continued conversation of how much data we will need to present over time. Of course, when we complete these trials next year, we will have additional exposure from our open-label extension study, both in DUPLEX and PROTECT as they complete and read out next year. And additionally, assuming we get approval, we will have patients who have gotten commercial therapy to be able to submit that data. So it will be a continued conversation over time.
Unidentified Analyst
Okay. Awesome. Thank you.
Eric Dube
Thanks, Justin.
Operator
We will take our next question from Tim Lugo from William Blair. Please go ahead, sir.
Tim Lugo
Thanks for taking the question and congratulations on the progress. We see REMS become something that is maybe proprietary for companies that have implemented them for certain therapies. I guess what are your thoughts on maybe a REMS could dampen uptake could also impact the sale value of the sparsentan franchise? And then maybe can you discuss the possibility that then the REMS program may be is a bit different for certain patients cell groups. I’m thinking maybe fragmentation or patients on certain concomitant therapy.
Eric Dube
Yes, Tim, thanks for the question. And I’d say, first, we will be able to assess the full impact once we have alignment with FDA on the final design of the REMS. But based on our work and assumptions to date, we believe that it shouldn’t have a major impact on the uptake or the impact on practices. And I think as Jula alluded to, what we see is that whether it’s monthly or quarterly, this is very much aligns with how many of these patients are being treated for their condition anyway. And I’ll turn it over to Jula on the rest of the question.
Jula Inrig
Yes. Just to clarify, Tim, was your question around how they’re going to monitor for embryofetal toxicity? Can I get a clarification on that and subgroup?
Tim Lugo
Yes. I guess, sure. I mean, I’m just thinking any sort of different monitoring and certain subgroups versus others. And maybe how that could alleviate FDA concerns, if you include monitoring on fragmentation versus broader monitoring?
Jula Inrig
Well, let me clarify that everyone’s going to have to sign up for embryofetal toxicity, and this is a consistent thing that is done for all patients to confirm their reproductive potential. So across the ERA class, every single participant will have to sign up and document that because you cannot confirm what their reproductive potential is going to be. And there’s education around that upfront when they get a prescription. It’s pretty simple, and they attest to it. And then there’s a monthly pregnancy testing that’s done for people who can become pregnant, and this is a cross class.
Tim Lugo
Okay. All right. Thank you.
Operator
We will take our next question from the line of Liisa Bayko from Evercore ISI. Please go ahead, ma’am.
Liisa Bayko
Hi there. Thanks for taking the question. Could you talk about your timing for final data? The final data was at eGFR end point. When do you think you might have that? When you will be prepared? Do you think to file with FDA? Do you think it’s going start to address some of the concerns? And then — yes, that’s my perspective.
Eric Dube
Okay. Thanks, Liisa. It was a little bit difficult to hear. So let me just confirm, you’re asking for confirmation of the timing of the final data from our trials as well as what our expectations are about those data, including eGFR addressing any questions from the FDA. Is that right?
Liisa Bayko
Yes. Sorry, I’m on a plane and [indiscernible].
Eric Dube
That’s okay. That’s all right. Well, thank you for joining the call. So, yes, I think we are on track as we’ve guided throughout the year that the final data from DUPLEX will be available in the first half of next year. And then the final 2-year data from PROTECT will be available in the second half of next year. And as we get closer to bringing the data sets in-house, we will be able to further refine the timing perhaps in a tighter window.
But we are on track for delivery of those data sets, and we will certainly work diligently to package those for submission to the FDA, both for full approval for IgA nephropathy or full approval as an sNDA for FSGS, but also in assessing the safety data to assess the potential for any adjustment or removal of liver monitoring as part of the REMS. So I think we will be able to make further kind of assessment once we see those data and have further conversations with the agency. But at this point, I think that’s certainly our intent and the plan for next year.
Liisa Bayko
And can you remind us on the size and duration of the database?
Eric Dube
Sure. And I’ll turn that over to Jula in terms of the size and also what data will be part of that submission.
Jula Inrig
Yes, certainly. So for DUPLEX, recall that we have about 370 patients who got randomized to active treatment versus sparsentan. So we will have that. And realize that patients are eligible to roll over to active treatment with sparsentan once they complete the 2-year trial. So we will have patients who have rolled over through additional data. For the PROTECT trial, we have about 404 patients who got randomized to sparsentan versus active control. And again, similar study design that the patients who got irbesartan will then roll over.
So we will have additional exposure in those open-label extensions where patients roll over to active treatment. So in totality, roughly about 800 patients. And again, we had significant patients in the early days of hypertension, where we have patients, but shorter duration of exposure in some of those early studies. And then additionally, we have the DUET study, which has about 108 patients, who got exposed to different doses. And we have patients who have now been on treatment for really up to almost 7 years now.
Liisa Bayko
Great. And when you look at other packages that other companies have filed to get lever testing the move, what size of — what duration are you seeing out there — of data that was presented there?
Eric Dube
Yes. It’s difficult to say, I think, particularly because within this instance, we know that FDA and the cardiorenal division is looking it through the lens of Subpart H accelerated approval. So we haven’t heard anything with regard to a particular threshold or number of patients. It’s really particularly based on an evolving data set within the diseases that we are studying. So I think if we do certainly find this — find further kind of insights, we will share those as we’ve tried to do along the way.
But I think the other aspect that I would just remind you, Liisa, is that this is a rare disease and the others were in non-rare and were submitted for full approval. So I think it’s a unique situation that we continue to navigate and certainly we will provide FDA with a much more complete data set when they are finished next year.
Liisa Bayko
Thank you so much.
Eric Dube
Thank you.
Operator
We will take our next question from the line of Laura Chico from Wedbush Securities. Please go ahead, ma’am.
Laura Chico
Good afternoon. Thanks for taking the question. I wanted to follow-up on one earlier comment, Jula, that I think I heard — I apologize if I didn’t hear this correctly. I think you said sparsentan is showing ALT/AST elevations that were comparable to irbesartan in the studies. If I recall correctly, irbesartan rates of ALT/AST elevations, I think, are low single digits. I’m not sure if that’s correct, but wondering, is it comparable in terms of the rates of instance or in terms of the magnitude of increase? Or is it both with respect to sparsentan? And then I have one quick follow-up.
Jula Inrig
So we collected with regards to rates of increases because that was our pre-specified adverse events of interest. And that adverse event of interest was 3x the AST/ALT elevations, which we monitored prospectively and also submitted to our DSMB for monitoring. And that’s what we’ve released that similar between the two arms and comparable.
Laura Chico
Got it. Okay. And then I apologize if you have not disclosed this, but can you confirm with the elevations you’ve observed so far with sparsentan in the IgAN setting? Or has this been FSGS dosed patients? Thanks very much.
Jula Inrig
Across the trials. So we’ve looked at it in totality.
Laura Chico
Got it. Thanks.
Operator
We will take our last question from Ed Arce from H.C. Wainwright. Please go ahead, sir.
Ed Arce
Great. Thanks for taking my questions and congrats on the progress in the quarter. A couple of questions from me. Firstly, I just wanted to confirm sort of some perspective share here today on the call with regard to the liver monitoring in the REMS. As you said, you’ve taken a second fresh look now over the last couple of weeks at some analogs and the history there. And I think you had said that really, you don’t expect as others haven’t any impact to utilization ultimately. Question is, a couple of weeks ago, you had mentioned and I think you mentioned earlier today, a more gradual uptake is your impression. So I just wanted to clarify that although the longer term remains sort of unchanged that you’re really more focused on the initial uptake part that could have a little more gradual uptake? And then I have a follow-up.
Eric Dube
Thank you, Ed, for the question, and that is a correct assessment that we’ve made. We believe that the need for liver monitoring and REMS does not change the addressable population nor does it change the clinical profile of sparsentan or the unmet need. But we do recognize that this will require some additional education of nephrology practices as well as just having clinicians and patients sign up initially. And so that, we do believe is going to have that impact short term. But certainly, long-term, we believe that, that is not going to be an issue, and that’s really what we’ve gleaned from others who have launched successfully with the REMS. And as we have mentioned previously, we will continue to refine those assumptions and provide any guidance once we’ve completed the market research to make sure that we have a contemporaneous view of our launch assumptions.
Ed Arce
Okay. Understood. Thanks for that. And then secondly, just turning to pegtibatinase, what are the barriers that FDA is considering before accepting total homocysteine as the pivotal study primary endpoint? And what gives you confidence that ultimately you would be successful in securing that? And in that regard, does this fixed cohort data from COMPOSE play any role in that? Thank you.
Eric Dube
Yes, thank you for that question. Particularly on pegtibatinase, as we closed out October, which is homocystinuria awareness month, it’s one that we recognize is certainly a community that has a high unmet need. And I think that’s really driven our desire to have a biomarker endpoint, which will facilitate the next phase of development. I’ll ask Bill to talk a little bit about what that might entail and what we believe FDA may be looking for. Bill?
William Rote
Certainly. We’ve gone through several interactions with the agency discussing the utilization of total homocysteine as an endpoint. We believe that we’ve gotten agreement there. From a big picture view of using total homocysteine as the primary endpoint in a Phase 3 pivotal trial. But what we haven’t completed and is an important detail is the — are the specifics of that trial and how you utilize it is that endpoint as a threshold or a percent reduction, the overall design of the trial, that work — we’re still working on with the agency and having received breakthrough therapy designation.
We have a multidisciplinary meeting coming up before the end of the year and then subsequent interactions are a little bit easier to have under breakthrough. So we look forward to having those discussions. You asked also about the sixth cohort. That is testing a higher dose as well as a lyophilized formulation. So we need to see the data in order to make a final dose selection and to confirm the safety and tolerability to lyophilize formulation as opposed to the liquid formulation that was in the earlier. So it’s on the path to Phase 3, but it’s not gating to further discussions around trial design.
Ed Arce
Great. That’s helpful. Thanks so much.
Eric Dube
Thank you, Ed.
Operator
That concludes today’s question-and-answer session. At this time, I will turn the conference back to Ms. Eichenbaum for any additional or closing remarks.
Naomi Eichenbaum
Great. Thank you, everyone for joining us this afternoon to learn about Travere recent updates. We have exciting milestones ahead and look forward to sharing more updates along the way. Have a great rest of your day. Bye-bye.
Operator
That concludes today’s conference. Thank you for your participation, and you may now disconnect.
Be the first to comment