Travere Therapeutics, Inc. (TVTX) Earnings Call Transcript & Summary

Good morning, and welcome to the Travere Therapeutics Corporate Update Call. Today's call is being recorded. At this time, I would like to turn the conference call over to Victoria Prescott, Manager of Investor Relations. Please go ahead, Victoria.

Thank you, Jenny. Good morning, and welcome to Travere Therapeutics corporate update call to discuss our regulatory update for FILSPARI in FSGS. Thank you all for joining on short notice. Today's call will be led by our President and Chief Executive Officer, Dr. Eric Dube; and Dr. Bill Rote, our Senior Vice President of Research and Development. Our Chief Medical Officer, Dr. Jula Inrig, will join us for the Q&A. 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. In addition, any forward-looking statements represent our views only as of the date such statements are made, February 11, 2025, 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.

Thank you, Victoria, and good morning, everyone. As most of you know, FILSPARI or sparsentan is approved for the treatment of IgA nephropathy. And with its novel approach inhibiting both the endothelin and angiotensin pathways together, it is becoming a foundational treatment option for the more than 70,000 patients with IgAN in the U.S. that we believe are addressable. Today, we are excited to be discussing the potential for an additional indication for FILSPARI in FSGS. Despite being a leading cause of kidney failure, there has been little innovation in FSGS over the last several decades, and there are no approved medicines indicated for people with this rare kidney disease. Based on our development program, including robust data generated from our Phase III DUPLEX and Phase II DUET trials, we have long held the belief that FILSPARI could be an important treatment option for people living with FSGS. I am pleased to share this morning that following the completion of our Type C meeting with the FDA, we are moving forward with our plans to submit an sNDA seeking traditional approval of FILSPARI in FSGS. Importantly, our submission will leverage the strong results from DUPLEX and DUET, 2 of the largest interventional clinical trials conducted in FSGS to date. And these data from DUPLEX and DUET align with the recent PARASOL group analyses that support the use of proteinuria in clinical trials for FSGS. Bill will go into a bit more detail shortly, but we are in position to complete our sNDA preparations and submit to the FDA around the end of the first quarter. As with any medicine, the potential approval of FILSPARI will be based upon FDA review. If our submission is accepted and granted priority review, FILSPARI could become the first approved medicine for people living with FSGS in the U.S. by the end of this year. Let me now turn the call over to Bill to provide additional insight into our engagement with FDA and the next steps. Bill?

Thank you, Eric. We are encouraged to see continued progress for patients living with FSGS. After reviewing the DUPLEX top line data with the FDA in 2023 following the 2-year readout, they communicated that the data from the Phase III DUPLEX study alone were not sufficient to support an sNDA submission at that time. The FDA acknowledged the work being done by the larger nephrology community to better understand proteinuria and eGFR as endpoints in clinical trials of FSGS and indicated a willingness to continue to engage with us on a potential path forward for sparsentan in FSGS following our consideration of additional evidence. Since then, work by the PARASOL group, a multi-stakeholder effort that includes patients, nephrology experts, regulatory agencies, including the FDA and industry representatives has elucidated the challenges regarding eGFR as a feasible endpoint in a Phase III trial in FSGS while generating highly supportive data for proteinuria as a potential endpoint. The analyses from PARASOL were generated for more than 20 databases collected worldwide, encompassing over 1,600 adults and children with FSGS. Specifically, the PARASOL group aligned on the observation that a reduction in proteinuria over 24 months is strongly associated with a reduction in the risk of kidney failure in patients with FSGS, including responder definitions based on thresholds of proteinuria that are both biologically plausible and strongly supported by the epidemiologic data. The PARASOL findings further support the meaningfulness of the proteinuria reduction observed with sparsentan in our FSGS program. The purpose of our Type C meeting with the FDA was to align on the contents of a potential submission for FILSPARI in FSGS in light of these findings from the PARASOL work group. As Eric highlighted, we're pleased with the outcome of our meeting and to be moving forward with an sNDA submission using the compelling data from DUPLEX and DUET. I'd like to touch on both of these data sets briefly. In the Phase II DUET study, FILSPARI reduced observed proteinuria by more than 2x that of the active comparator irbesartan at 8 weeks, achieving statistical significance. More patients also reached the modified partial remission endpoint, which measured the ability to achieve a 40% reduction in proteinuria from baseline and UPC below 1.5 grams per gram. And in the open-label extension, with a median follow-up time of approximately 4 years, 43% of patients receiving FILSPARI achieved complete remission or UPC below 0.3 grams per gram. Those patients who reached complete remission at any point in the time achieved approximately 80% proteinuria reduction on average and experienced slower kidney function decline with negligible kidney failure rates over the period of observation. In the Phase III DUPLEX study, FILSPARI achieved a significant treatment effect on the primary interim endpoint of modified partial remission at 36 weeks, which was sustained over 2 years. The full 2-year results published in the New England Journal of Medicine showed a significant treatment effect compared to irbesartan at proteinuria thresholds from 1.5 gram per gram down to complete remission or 0.3 gram per gram. Consistent with the PARASOL findings, the treatment effect of FILSPARI versus irbesartan strengthened as thresholds became stricter. In fact, in every way we have evaluated proteinuria reduction for FILSPARI, it has been superior to maximally dosed irbesartan. And while DUPLEX was not powered for statistical significance on hard outcomes, kidney failure rates were nearly double with irbesartan compared to FILSPARI with a 42% reduced risk of kidney failure for patients receiving FILSPARI over the 2-year study. Our teams are in a position to submit a high-quality sNDA around the end of the first quarter. If accepted and granted priority review, we could see a potential approval later this year, and we look forward to working with the FDA throughout the sNDA review process. Now I'll turn it over to Eric for his closing remarks. Eric?

Thank you, Bill. As we've outlined today, we are pleased with our recent FDA interactions and to be moving forward with the submission of an sNDA for FILSPARI in FSGS. The DUPLEX and DUET data, alongside the broader work by the PARASOL group, reinforce the important role of proteinuria reduction in FSGS, and we are encouraged by the FDA's engagement in this process. We recognize the urgent need for new treatment options and continue to believe that if approved, FILSPARI could become a foundational treatment for people living with FSGS. We look forward to keeping you updated as we continue this important work. Now let me turn the call over to Victoria for Q&A. Victoria?

Thank you, Eric. Jenny, we can now open the line up for the Q&A.

[Operator Instructions] We will now take the first question from the line of Vamil Divan from Guggenheim Partners.

Congrats on the progress here. I guess I'll take my one question I just want to focus on is around the endpoints here. We've had a lot of discussion with investors over the last few months post PARASOL. And is there a specific endpoint or a specific analysis that the FDA is focused on in FSGS? As it feels like it's more the totality of the data, but I'm just curious if you can share based on your discussions, was there specific new analysis or cuts of the data that the FDA has requested that they may be particularly focused on as they conduct the review. I'll get back in the queue.

Thanks so much, Well, I would say that our plan -- our meeting certainly went according to our plan and the work that we've done. Bill, would you like to provide any additional detail on that question?

Certainly. While we typically don't share specific details about regulatory engagements unless there's something that's material to communicate, what we can say is the agency provided guidance on what would be helpful to them in reviewing our submission, and that's generally to put our data from DUPLEX and DUET into context and relate them to PARASOL. We have what we need, and we're in a position to complete our submission around the end of the first quarter.

Your next question is from Anupam Rama from JPMorgan.

Congrats on the update. I wanted to follow up a little bit on Vamil's question, right? Like do you have any color from the agency on proteinuria specifically? Like are they going to be thinking about absolute change, the categorical changes or the threshold changes that you mentioned earlier? Or is this like Vamil said, like the totality of the proteinuria data that's really important here?

Anupam, thanks for the question. Bill, I'll have you take that one as well.

Sure. I think if you look at it in a totality perspective, I think that's a good way to look at it. Whether you look at proteinuria over time or you look at a specific point in time or you look at thresholds as were published in the New England Journal article, the story is essentially the same across all of those analyses that you have a clear separation between treatment and active control and that sparsentan is superior in each of those analyses. So that would be the way I'd guide you to look at that.

Yes. The only thing that I would add is that those thresholds that we had in the New England Journal will be in our submission, and those proteinuria thresholds were all prespecified. So I think it is -- when you take a step back, totality of the data, certainly, we believe, is a very strong aspect of how this sNDA will be and is being constructed.

Your next question is from Tyler Van Buren from TD Cowen.

Congratulations on the update. So just a follow-up. Obviously, you just discussed the proteinuria thresholds, but was there alignment with the FDA on a specific proteinuria cutoff? I just asked because the PARASOL proposing the cutoff of 0.7 grams per gram is the basis for full approval.

Sure. Jula, would you like to take that and talk a little bit more about the 0.7 grams per gram with PARASOL relative to what we have in our analysis?

Certainly. Well, we didn't get a specific request for a specific threshold such as 0.7, for example. What we have is data that shows a significant treatment effect across all thresholds that we look at. And as Bill mentioned and Eric mentioned, the more stringent you go down to complete remission, we see an even greater treatment effect favoring FILSPARI over irbesartan. And so we believe we have everything we have, and we'll complete our file for submission at the end of this quarter.

Your next question is from Joseph Schwartz from Leerink Partners.

This is Will on for Joe. And I'll add my congratulations on the progress here. Just one for us regarding the label for FSGS. Could you provide a bit of color commentary on your base case expectations here? And as this is for full approval, is it fair to assume that the label could be similarly as broad as the full approval in IgAN? And then just for the 40,000 addressable patients, what are the assumptions here to get to that figure?

Sure. I'll take the addressable population analysis and Bill can take the question on label, which I think is a bit early, but certainly, we can provide some commentary relative to what we studied. So when we look at the population, the population of patients with FSGS and that's primary and genetic FSGS, it's just under half that of IgA nephropathy. And our team has done quite a bit of work to understand the epidemiology. When we look at those patients that are addressable, it's probably closer to 30,000 patients, and those are patients that are diagnosed. They're under the care of a nephrologist, which most of these patients that they're diagnosed are. They've got biopsy-confirmed FSGS, and they're not so far along in their kidney function that they would be in or near kidney failure. So when we look at those criteria, that's what gets us to not just what the 40,000 is, but what would be addressable closer to the 30,000. And I'll turn it over to Bill for the label question.

Sure. Well, thanks, Will. And I think you are correct. Because we have an application for full approval, we would expect that we would have a fairly simple indication statement. As Eric noted, this still needs to be negotiated through the review process, but it should read something along the lines of FILSPARI is indicated for the treatment of FSGS in patients 8 and up because that would match the population that we studied, and it should be similar and parallel to what we have in the IgA nephropathy indication.

Your next question is from Yigal Nochomovitz from Citi.

This is [indiscernible] on for Yigal. Congrats on the progress. Just wanted to ask after the Type C meeting, did you discuss any additional analysis based on these results that you might have been requested to be done or anything like that? I know that was a possibility in preparing for the data from the DUET and DUPLEX study is sufficient.

Okay. Thanks so much for the question. Just to make sure it was a little bit hard to hear. You're asking if in the Type C meeting, there were any additional analyses that were requested within DUET and DUPLEX, is that correct?

I just want to based on the PARASOL results. I know you mentioned...

Based on PARASOL.

Preparing for and things like that? Or I guess, were the DUET and DUPLEX study is sort of sufficient evidence to kind of move forward?

Yes. Okay. Yes, absolutely. The data from our Phase II and Phase III were sufficient. Bill, would you like to provide any further commentary on that?

Yes. So the submission is based on those 2 studies and the data in total from those studies. Keep in mind, these are 2 of the largest studies ever run, or just interventional clinical studies in FSGS to data, and that gives us confidence in the data, and they're very consistent between the 2 and show that statistically significant delta between sparsentan and irbesartan across all the range of measurements that we've had. So the submission with respect to PARASOL highlights our results in relation to the observation from PARASOL and puts it into context for the reviewers.

Okay. I think that's the important component is that it provides even greater context for the importance of not just proteinuria, but also what our results might mean.

Your next question is from Laura Chico from Wedbush Securities.

I guess what I -- what is the potential for an advisory committee meeting to be convened and realizing this is an sNDA application and obviously already approved in IgA nephropathy. But given the novelty in the FSGS space, I guess, could you speak to the potential for an advisory committee meeting?

Certainly. Bill, would you like to take that one?

Sure. We will likely learn whether or not the agency is choosing to call an AdCom at the time of acceptance of the submission. So that should come about 60 days after submission. In the context of PARASOL and the shift from eGFR to proteinuria in FSGS, we recognize that this could be precedent setting in their decision. And with that in mind, it wouldn't be surprising if the FDA requested an AdCom. We'll certainly be prepared if an AdCom is scheduled, that would give us the opportunity to highlight the data and put it in context for that group. So we'll be prepared should that be the case.

Your next question is from Maury Raycroft from Jefferies.

Congrats on the update. I just wanted to ask a clarification question based on an earlier one. Are you incorporating any supporting open-label extension data from the DUPLEX study into your analyses and the NDA filing? And then what is your latest thought on the market research? Or what's your latest market research on how many patients are out there that could be addressable at launch?

Okay. So I'll take the addressable population, and I'll have Bill speak about the OLE data. Our research has certainly been consistent over the number of years that we've been looking at who might benefit. And this is where today, we believe that it's around 30,000 patients that would be addressable. With that said, we would expect that this could grow as we see within other rare diseases. There is definitely a high level of awareness of this trial and the potential within and amongst the nephrology community, certainly a growing awareness within the patient community. And so we would expect that this could lead to more biopsies earlier biopsies as we are starting to see within IgA nephropathy, which could lead to an increase. And again, the thing that I would point out is that, that 30,000 addressable and that 40,000 patients broadly with FSGS really is specifically those patients with primary and secondary FSGS. And I'll hand it over to Bill about the open-label extension data.

Thanks, Eric. The open-label data for both the DUET study and the DUPLEX study are included in the submission as strong supportive data for long-term safety data along with the IgA nephropathy data set. So we have a very large and growing safety database. The primary efficacy analysis are all based on double-blind periods of the study. The data from any of the open-label extensions provides supportive data. But the key is really the results from the double-blind DUPLEX study.

[Operator Instructions] Your next question is from Liisa Bayko from Evercore ISI.

Yes. Just a couple of questions for me related to timing of the review. Are you expecting 6 months? This is an sNDA. If you could walk us through timing there? And then also, do you expect to inherit the same REMS protocols you already have on the label for IgA nephropathy?

Thanks, Liisa. Bill, I'll turn that over to you.

Yes. It's an sNDA. So if we get priority review, that would be a 6-month clock. If we end up with a standard review, that would be a 10-month period. We certainly are requesting priority review. With respect to the REMS, we anticipate that the FSGS will be an indication that's added to the current label. We have a PDUFA date to modify the frequency of liver REMS for IgAN, and it would be the overall FILSPARI label by that point in time or at some point in the future. That PDUFA date is August 28, 2025. Given the high unmet need in the population of patients with FSGS, we don't see REMS as a barrier for this indication, which is consistent with the feedback that we've been receiving from both physicians and from patients.

Your next question is from Prakhar Agrawal from Cantor.

Congrats on the update. I just had one. So do you plan to submit any eGFR data even from the open-label extension trial? Has the FDA provided any feedback on this and whether there was any discussion on eGFR data at all in the Type C meeting?

Okay. Bill, I'll hand that over to you.

Yes. The eGFR data is, of course, part of the study and is included in the submission from the double-blind portion of the study. The open-label extension is still ongoing. It's important to note that during the Type C meeting, the discussion was around the content of the submission and how that's packaged around proteinuria. The discussion didn't focus on eGFR. It's really downstream of PARASOL, how do we put our data into a format that's best supportive of the agency's review in the context of the PARASOL outcome.

Your next question is from Jason Zemansky from Bank of America.

Congrats on the updates. Maybe at a high level, what sort of ancillary efforts are needed to launch in FSGS beyond IgAN? I mean are there any prelaunch activities underway right now? And kind of what sort of near-term SG&A impact should we expect?

Yes, Jason, thanks for the questions. We certainly will be looking to invest first to make sure that we are educating nephrologists around the importance of proteinuria. This is a shift in the paradigm as many nephrologists are taught that eGFR really is the best predictor across many of these diseases. And certainly, as PARASOL has now taught us, proteinuria is associated independently of the rate of progression to kidney failure in FSGS. So first and foremost, it's about education. There will be an investment to make sure that we're able to cover not just nephrologists treating IgA nephropathy, but also FSGS. So there would be an expansion of our organization. This is incremental given that there is a high degree of overlap in physicians that see patients with IgAN and FSGS. It's about an 80% overlap. We'd also look to expand our coverage for pediatric nephrologists, if approved, because we assume that we will be approved for pediatric patients with FSGS, given that's what we studied. So that would come in time. And then another effort for investment is to make sure that we can help in identifying these patients earlier. This is a disease that is rapidly progressing. And so time really matters. And so it's not just about education. It's about making sure that we can identify and engage these patients as early as possible. This certainly would increase our SG&A, but it wouldn't be a doubling of what we see in IgA nephropathy. There's a lot of overlap in the efforts here. And some of those initiatives will be -- and investments we'll be looking to make and are making now to make sure that we can be prepared, assuming the time line that Bill laid out for approval under a priority review time line.

And your next question is from Mohit Bansal from Wells Fargo.

I'll add my congrats as well. So my question is regarding the biological possibility part of the submission. So do you -- in your conversations, is FDA satisfied with the PARASOL group finding regarding that? Or you need to submit some incremental data to support that for traditional approval for proteinuria endpoint?

Great. Thanks for the question. Jula, I'll turn that one over to you.

Well, thanks for the question. Well, we believe we have everything we need with regards to the biologic plausibility. Certainly, it's part of our submission in addition to what was shown at PARASOL that eGFR isn't a feasible endpoint, but proteinuria is in the causal pathway of this disease. And so we are using a lot of the PARASOL results as well as our own to support proteinuria as biologically possible. So we feel confident in our package and submission and the data that we have to support proteinuria as an endpoint for full approval. I want to clarify that.

Your next question is from Greg Harrison from Scotiabank.

This is Joe Thomas on for Greg Harrison. Congratulations on the update today. We're just wondering how have conversations with payers been going in FSGS? Like what feedback have you received? And what impact has PARASOL had on that front?

Yes, Joe, thanks for the question. Our work with payers on FSGS certainly has been ongoing over the years, given that we've been working in this space for some time. Payers certainly that we've engaged with recognize the unmet need in FSGS. This is -- although it is a rare disease and the epidemiology is less than half that of IgA nephropathy, it's one of the leading causes of kidney failure. and payers recognize that. They also recognize that the recurrence rate after a transplant, which can be such a significant investment is nearly half, nearly 50% of patients that have a transplant have recurrent FSGS, which can be devastating for those patients and their families. And so there is a recognition of the need of something like FILSPARI. So the work that we're doing with payers is certainly to educate them around the disease as well as to build an evidence-based package to be able to support the economic value of FILSPARI. Much like we have and are doing in IgA nephropathy, our goal with payers is to gain broad access given the mechanism of action, given our intent to have FILSPARI as a foundational therapy for these patients our goal overall with payers is to make sure that there is broad access. We've been successful to date with IgA nephropathy, and we would expect to do the same thing with FSGS if approved.

Your next question is from Alex Thompson from Stifel.

Congrats on the update here as well. I guess I'm curious during the Type C meeting, whether or not FDA suggested that they might like to see you run another study or if they are fully supportive here of the submission of existing data from DUET and DUPLEX.

Yes. Alex, I'll take that question. We have all of the data that we need for the submission, and that was not raised in the Type C meeting.

Your next question is from Ed Arce from H.C. Wainwright.

Let me add my congrats on the real turnaround here moving forward with this program. My question is just in the context of PARASOL, what specific data is the FDA relying on to support this as a full approval pathway, specifically with regards to the direct impact on kidney failure?

Sure. Jula, why don't you take that question?

Well, in the context of PARASOL, what was demonstrated, as we said earlier, that eGFR is feasible, but proteinuria is biologically plausible. And as you may recall, at the PARASOL meeting, there wasn't one specific metric or threshold. But as you got more stringent all the way down to complete remission, you saw an even more meaningful effect on avoidance of kidney failure over the long term. And I would say what's really important is that our data is supportive across all the thresholds of a meaningful treatment effect with FILSPARI over irbesartan, and that separation gets even greater all the way down to complete remission. So we believe our data is very aligned with the PARASOL data and supportive of long-term kidney function preservation that's consistent with what was shown in PARASOL.

[Operator Instructions] And your next question is from Vamil Divan from Guggenheim Partners.

So maybe just on the commercial side, a couple of quick follow-up questions. When you commented on the payer conversation, I'm just curious on the pricing, just given the dosing here is twice what it is in IgAN, is it reasonable to assume the price would just be twice as well? And then just the competitive landscape, any comments there? I mean with what you guys are leading and also just some of the PARASOL work, a lot of other companies now talking about FSGS as an opportunity. So just curious if you have any comments on what you're seeing on the competitive side?

Certainly. I'll take the first question on pricing, and I'll have Jula comment on other potential medicines in development. So what I would say is our strategy for pricing and access is that broad access for these patients. They've been waiting far too long for an approved medicine, and we want to make sure that, that is not a barrier for them. It is safe to assume that when you look at the target dose these patients are going to be -- adult patients would be on a target dose that is double that of IgA nephropathy. It's a bit premature for us to talk about pricing in detail at this point. Our focus is very much around getting this sNDAs in as quickly and with high quality as possible. But our teams are certainly working on what is the right pricing and access strategy to ensure that this can become the new foundational therapy in FSGS. And with that, I'll turn it over to Jula.

Yes. Thanks. Unfortunately, there has been a lot in development for this patient population with a high unmet need and studies have either stalled or stopped in early development. And there's really only one other company that's in Phase II/III that is years behind and could be complementary with sparsentan. And everything else is just starting as far as the Phase II. And most of them are a subset of the patient population such as primary FSGS or genetic FSGS or others and really far behind.

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call. I will now hand the call back over to Victoria.

Thank you, Jenny, and thank you, everyone, for joining today's call. We look forward to providing additional updates on our progress at future calls. Have a great rest of your day.

The conference call has now ended. Thank you all for joining. You may all disconnect your lines.