Hi, good morning everyone, and thank you for joining us. My name is Edward Nash, Senior Biotechnology Analyst on the Equity Research Team at Canaccord Genuity. I have the pleasure of having with us today Travere Therapeutics. With us from Travere, I have Chris Cline, who's the Chief Financial Officer. Thank you very much, Chris, for joining us.
Thank you for having us.
Maybe as we just start off, if you could maybe just give us some background for our audience on what it exactly is that Travere does, and then just the kind of clinical trial focus the company has.
Sure. For those of you that don't know Travere, we are a biotech company based out of San Diego, and we are exclusively focused on identifying, developing, and delivering life-changing therapies for people living with rare disease. Core to our focus is rare nephrology and rare metabolics. Really at the heart of our efforts is FILSPARI, which is the only dual endothelin angiotensin receptor antagonist that is approved for IgA nephropathy and in development for FSGS, two rare kidney diseases. Both are leading causes of end-stage kidney disease or end-stage kidney failure.
We also have a program called pegtibatinase that is an enzyme replacement therapy that is we're looking to begin enrollment next year in our phase III study, and that's looking to be the first potentially disease-modifying therapy for something called classical homocystinuria or HCU, where there's currently no real therapies that are disease-modifying or that are really benefiting patients. We're in the early stages here of being able to help patients and looking forward to a very exciting second half of the year.
Fantastic. FILSPARI received accelerated approval in February of 2023. The drug has been on the market now for about two and a half years. Can you talk a little bit about the commercial uptake, and have there been any major changes from what you initially planned with your commercialization?
Sure. From the outset, our goal with FILSPARI has always been to enable it to become foundational care in IgA nephropathy. If you think back to February of 2023 when we gained accelerated approval, we were the second therapy that was approved, the only non-immunosuppressive therapy at the time. You had physicians that knew to treat their severe patients but were still learning how important it was to treat those patients with lower proteinuria. Under accelerated approval, all therapies have a little bit narrower labels, so they're labeled for generally 1.5 g and above. During that period, as you might expect, you have the initial blocking and tackling of your commercial launch where you're working through reimbursement, you're working through the fulfillment process and getting your therapy out to patients, and you're also building that experience with physicians and patients.
What we saw in that initial period was a very nice uptake, very consistent with what our expectations were in setting that foundation for becoming the new treatment standard. We were able to outperform all of the benchmark launches in the recent renal space. What we really looked to do was leverage that experience when we got to full approval, which was September of last year, to go from roughly 500 PSFs or patient start forms in demand up to what is now the new baseline of around 700 patient start forms in demand. A nice jump. That's been driven by the fact that we now have a broader label that is for patients at risk of progression, so there's no more cutoff of 1.5 g.
We've also seen a nice evolution in the KDIGO guidelines, which has helped not only drive physicians to be more ambitious in how they're treating their patients, but also places FILSPARI as foundational care and is really changing how people are thinking about things going forward. We've seen a nice acceleration now in full approval, and we're looking forward to a strong second half.
You've talked about the new patient forms, and we obviously hear a lot about that every earnings call because that's really a good guide as to what uptake is looking like. Could you speak a little bit about reimbursement? How long does it normally take for a patient to complete that form before the drug actually gets in their hands, and how has that changed and evolved since initial launch?
Sure. As part of our strategy, we had always planned to have broad access for FILSPARI. You know that started prior to launch when we were engaging with payers. It continued with our pricing strategy at launch, and it continues today with continuing to engage with payers and making sure that the updated label is reflected and we have strong access. We've been very pleased with the progress. When you think about our payer coverage, we've got 96% of patients with access to or a pathway to access, and we have seen a nice transition of payers reflecting the updated label. That's all gone very well. To your question on the timeline and how that's evolved, our Chief Commercial Officer, Peter Heerma, typically talks about his benchmarks being the 20- 60-day timeline.
As you would imagine, early in the launch, you start at the further end of that as you're still working through the reimbursement process, getting the payer coverage plans in place, getting the infrastructure up to full speed, et cetera. We've seen that consistently go towards the lower end, and we're continuing to invest there and continuing to see improvement every quarter. Things are moving very well.
That's great. You have a supplemental NDA in front of the FDA with a PDUFA at the end of this month. Can you remind us of the supporting evidence that led to the filing and how you feel about the outcome as far as getting the REMS right now modified?
Sure. The SNDA that you're referencing, for anybody that may not know, is an SNDA to modify our REMS for really two purposes. The first is to remove the embryofetal toxicity monitoring from the REMS. That's a class-based change that FDA had communicated to us along the way, and we included that in our request for the SNDA. We would expect that to just go into the normal labeling aspects. The second is around liver monitoring. The way that FILSPARI is currently structured, or the REMS is currently structured, is that patients have to do monthly monitoring for the first year and then transition to quarterly monitoring after the first year. Our request to FDA in this SNDA is to have quarterly monitoring upfront and have that be the way throughout treatment for patients. The rationale behind that is that's how we study the drug.
We did quarterly monitoring in our clinical trials, but also it aligns very clearly with how patients are normally getting their labs. It makes it convenient and aligned very well with their normal cadence of their doc visits. In terms of the evidence, there are a host of things that we included in our SNDA. The first and foremost would be our clinical trials. In our clinical trials, we show that FILSPARI had comparable ALT/AST elevations relative to irbesartan, the active control. That is in both IgA nephropathy and also in FSGS where we trialed double the dose. We have had no cases of Hy's law or any kind of elevated ALT/AST associated with bilirubin, etc. , in the course of the program. That's one aspect of it that has been very consistent. The other now that we've been able to strengthen that submission with is real-world data.
As we talked about earlier, FILSPARI has been approved for some time now, and we've been able to capture that data in the real-world setting to show that there have been no cases of Hy's law and that we're seeing that the monitoring that has been in place has been more than adequate, but that it can go to quarterly. To your point, we expect that to be the case when we get to the PDUFA date of August 28th.
Is the expectation over time to get the REMS removed entirely, and this is just the first step towards that, or is it just something that will likely need to stay? It made it easier, obviously, being on the same schedule as what a patient normally does their lab work.
Sure. Having it on the same schedule is certainly going to be helpful, but our goal is to ultimately have it removed. It's always been a two-step process. First, this one is to modify it to that quarterly and get it into the normal cadence of things. Ultimately, we believe that we have the data and we will have the data to get it removed. We're going to continue to have that dialogue with FDA. Historically, they've been anchored on our post-marketing requirement, which is 3,000 patients for two years. We're going to continue to engage with them to see how quickly we might be able to get it removed.
Is this more about making the burden easier on the patient, or does this actually, with having a REMS in place, actually tend to deter some physicians from using the drug?
Yeah, I don't think it's had a big impact on physicians. For physicians, it's relatively straightforward. You go through, you certify that you have read the REMS documents and the label. It's a relatively quick process. I think where we are expecting the most benefit is from it's really convenience for patients. There's probably a small segment of patients that are either lower in their proteinuria or they have very busy lives that just think about a monthly monitoring is something that may be too onerous. For those patients, we think that it'll open it up a bit and fall right into that normal cadence of things.
Understood. Now with the IgA nephropathy development landscape, it has changed dramatically in the commercial landscape in a very short period of time, and it's gone really from 0 to 60 over the past several years with Tarpeyo's approval and then FILSPARI, and then we've had a couple of approvals since then. Could you maybe talk a little bit about the more recent approvals in the space, FILSPARI and, I believe, another agent, and just has that in any way impacted how you're approaching the market from a commercial standpoint with FILSPARI?
Sure. It's an exciting time to be in IgA nephropathy for sure. We've been very pleased with our progress with FILSPARI, and we just reported second quarter results last week, and there we reported all-time highs for both demand and revenue. We're doing very well on our pathway to getting FILSPARI to foundational care, and we expect that to continue. When we think about the overall treatment paradigm in the landscape, we believe that there is going to be room for many therapies to continue to grow. I say that for two main reasons. One, for IgA nephropathy, we believe that there are more than 70,000 patients that are addressable, and that's likely to continue to grow. There are a lot of patients out there that are going to need help, and we know that there isn't any one therapy that is going to get all patients into complete remission.
That's an important component of where the KDIGO guidelines are headed. The second aspect of that is going back to the KDIGO guidelines. We have the draft form now. We're expecting the final guidelines later this fall, but they're highlighting a few important things, one being getting patients to complete remission or 0.5 g, which is a nice change from where physicians used to be, where they weren't as ambitious with their treatment and getting patients lower in their proteinuria. That's going to drive more and more treatment both earlier and also with utilization of the new medicines, including FILSPARI, as we move ahead.
The other important aspect is that the KDIGO guidelines are highlighting this dual approach of addressing both the overactivation in the kidney, which is where FILSPARI plays, and then overactivation in the immune system, which is where a lot of the other medicines that are coming in development are going to be most active. There's going to be the need for both, and with many patients out there that need help, we expect the market to continue to grow nicely.
With FILSPARI, from the new entrants that are out there, do you have a strong differentiation from those agents? I know you said the market's large enough for multiple competing agents, but just kind of wanting to understand what that differentiation is so that when you're going in front of that provider, you have that barrier to entry already, right? That you've already been out there for a longer period of time than what's out there. Does it require more convincing or more visits as you go to those providers to kind of differentiate FILSPARI from competing agents?
Sure. I think one of the benefits that we have that you touched on briefly there is that we've had FILSPARI in the market for some period of time. Physicians have already built up that experience, and what we continue to hear as feedback is that the experience they're having matches what we saw in the clinic. A rapid and sustained reduction in proteinuria early on when patients start treatment. We already have that to be able to leverage. In terms of thinking about FILSPARI versus some of the other therapies in development or available, FILSPARI is the only medicine that can replace standard of care, right? We're the only medicine that has been trialed specifically against an active control RAS inhibitor, and everything else is being used in conjunction with standard of care. That's a unique placement for FILSPARI.
We've also shown we're the only non-immunosuppressive agent that's approved under full approval for all patients at risk of progression. We've got the two-year data to be able to show that treatment with FILSPARI translates to long-term kidney function preservation, which is very important when talking about the kidney aspect of disease. When I think about the treatments that are coming down the line on the immune side of things, it's less about advantages and disadvantages. It's more about where do the synergies come into play because there are differences between us and the B cells. You think about it as treating the kidney versus the immune system, deposition of IgA versus protecting the nephrons that are still there, etc . Most importantly, the B cells, they're all being evaluated on top of standard of care, right? That's what we're aiming to replace.
The expectation based off of what we've developed in our clinical studies and evidence generation beyond that, alongside the KDIGO guidelines, is going to continue to place us as combination therapy with those in the future.
That's kind of where I was going next with APRIL/BLyS mechanism of action seems to be what's up next. They're in phase III now that we should see potentially receiving FDA approval. From what you're talking about, it doesn't sound like really the commercial positioning of FILSPARI will need to change at all with the addition of this potential additional APRIL/BLyS mechanism coming to the market.
That's right. Our goal is to have FILSPARI become foundational care, replace that historical standard of care that has been RAS inhibitors, etc. In doing so, we expect to be utilized alongside those other medicines that are really focused on the more immune aspect of the disease.
Got it. You have another PDUFA date that's coming up in January of 2026, and that's for it's very heavily watched on the street for the potential expansion of your label for the indication of FSGS. Could you talk a little bit about PARASOL workshop because that was obviously extremely important in filing for this supplemental NDA and just what the implications and outcomes from that meeting have on FILSPARI for potential approval in FSGS?
Sure. PARASOL was a very exciting evolution of the field, if you will. Taking a step back and looking first at the membership of PARASOL, you're talking about FDA, EMA, the leading patient advocacy organizations within FSGS, and then glomerular experts throughout the world. You're really bringing together the right people to try to solve the question of how do you evaluate FSGS in a clinical setting that's going to provide a pathway to a potential approval. What they did was they were able to access 26 different data sets, more than 1,600 patients' worth of data, which is one of the largest collections of data that we've seen in FSGS. They asked the question, is eGFR a feasible endpoint in FSGS? If not, what is?
The analysis led them to the conclusion that eGFR, while it is linked to understanding kidney failure, is not viable as a clinical endpoint in diseases like FSGS where you've got smaller populations. The main reason for that is the variability in eGFR measurements in FSGS, and that's really driven by the waxing and waning nature of the disease. PARASOL then went through the database and evaluated proteinuria and looked at it from a few different perspectives. One was the biologic plausibility, and it's very clear that proteinuria has strong biologic plausibility in the causal pathway of FSGS. Two, it was focused on what are the thresholds or what do you need to see in reduction of proteinuria to have a clear tie to kidney failure or understanding the risk of kidney failure.
What they found was that if you can get patients below 1.5 g, and they pointed to 1.5 g- 0.7 g, and even if you can get them below that, then patients have a far greater chance of avoiding kidney failure. That was very clear through the data. For us, when we looked at the PARASOL data and we held it side by side to our DUPLEX data, they fit very consistently. When we think about DUPLEX, our phase III in FSGS that completed a little while ago, and we look at the thresholds, you see as we go down from 1.5 g to 1 to 0.5 g to 0.3 g of proteinuria that you have a very strong response for FILSPARI versus irbesartan, and actually that signal gets stronger the lower down you go.
Furthermore, we reported some additional data earlier this year that shows in our DUPLEX study, if you achieved partial remission of proteinuria or complete remission, you had a 67%- 77% chance of avoiding kidney failure. We also had additional data that really points to the, you know, with partial remission of proteinuria, no matter at what time point you look at it, we continue to maintain a magnitude of benefit for FILSPARI versus irbesartan. Whether it was at any point in time in the study, whether it was at 36 weeks or whether it was at two years, you had the same magnitude of benefit. I think all of those align very nicely to the PARASOL data and to the fact that FILSPARI has been able to show a benefit over an active competitor.
I know you mentioned on the call that likely you've been signaled by the agency that they would most likely be having an adcom for this indication, which really is a typical standard of business. It's usually very unusual not to have one. I know you guys have been preparing for this. Is there anything specific? I also, as the analyst, completely agree. It seemed like what PARASOL was looking for and what data you had from DUPLEX did fit hand in glove. Is there anything that you kind of feel where the agency is maybe going to be spending a lot more time now that they've obviously are aware of what came under PARASOL that might be a concern or that might be just something that you know they're going to be really kind of focused on?
Sure. FDA has not yet communicated anything specific to us that they're planning to cover in the adcom. Based off of all of our interactions to date, I think it's fair to expect that there will certainly be some conversation of PARASOL. That's a new development over the last year that is shifting how people think about an endpoint that is changing, right? That will certainly be a part of the discussion. I think another important element that will be covered is putting the DUPLEX data into the context of PARASOL. I think that's especially important because our DUPLEX data were not involved or not incorporated into PARASOL. Our data are independent, and this would be the first opportunity for the FDA to really review in that forum the DUPLEX data and how they match, just as I mentioned, to PARASOL.
I think that will be a key focus in putting that into context. It's really a risk-benefit discussion, right, as most adcoms would go. From the benefit side, I just mentioned a number of areas where we see it's very clear that FILSPARI has that strong proteinuria reduction and ties very nicely to PARASOL. On the safety side of things, we have a drug that's been approved in IgA nephropathy, and I think it's a very well-defined safety profile that's been comparable to irbesartan that has been available for many years in multiple indications. I think we've got a very clear picture, and I feel like we will be very well prepared and have a good narrative for the adcom.
Great. Can you talk a little bit about the size of the FSGS market? Obviously, the street's very excited about it. You know, see it as a really big part of the expansion of FILSPARI, but just from maybe a patient number standpoint, give us an idea.
Sure. We're certainly excited about it as well. When we think about the FSGS market, it has the potential to be larger than IgA nephropathy. From patient numbers, it's a little bit smaller. It's actually about half of the addressable population of IgA nephropathy if you don't count secondary FSGS. The differences, and the main differences that drive our belief in having a strong uptake and strong utilization, would be multifold in that you have a differing sort of ambition or awareness of needing to treat the disease amongst nephrologists. In IgA nephropathy, it's taken some time to educate the importance of treating earlier and getting patients below 0.5 g or 0.3 g of proteinuria. In FSGS, nephrologists know, right? They're motivated. Patients are also very motivated, and they're actively seeking information and understanding of treatments coming through. You have a motivated patient and physician group.
You also have a built-in experience with FILSPARI, right? There's a fair amount of overlap between the nephrologists that treat IgA nephropathy patients and FSGS patients. We would anticipate that nephrologists will have a very good experience with FILSPARI and know quickly to use that in their FSGS patients. That's the feedback that we've been getting in a lot of our market research. We also have, it's double the dose of IgA nephropathy. Between those different dynamics, we believe that it has a very good opportunity for us to be able to help patients.
You're obviously targeting the same physician group as you are now with IgA nephropathy. Will anything else need to change with regards to the current commercial structure once FSGS, if it gets approved?
There is quite a bit of overlap. There is more than 80% overlap between nephrologists who are seeing IgA nephropathy patients and FSGS patients. We will be incrementally increasing our sales force, so a small expansion. The two goals there are first to maintain our share of voice in the IgA market that's becoming more dynamic. We want to make sure that we continue to make progress towards our goal of having foundational placement there. We also want to make sure we're getting to some of the pediatric nephrologists because that's something that we don't currently focus on in IgA nephropathy with a differentiated label. In FSGS, we studied pediatric patients in the study, and that's going to be an important component of where we want to make sure there's good access.
What is roughly the overlap in the physicians that treat FSGS and IgA nephropathy?
It's more than 80%.
Okay. Great. You mentioned the peds. When you're looking at the sales force, are you able to use the same existing sales force to then start looking at the pediatric nephrologists, or does that really require a different instrument from a sales standpoint to target the peds?
With a small expansion, we'll be bringing in similar types of sales reps. It doesn't require necessarily a specialty sales rep or a different type of phenotype. I think it's really going to be focused on rare disease and nephrology, and those are the areas that we have a very experienced sales force currently, and we'll be able to complement that very well.
Great. For the time we have left or less time, could you maybe just touch on pegtibatinase and what the status is for that for HCU?
Sure. Pegtibatinase, again, our phase III, our enzyme replacement therapy in phase III for HCU. We're making great progress on our optimization efforts for CMC, and our expectation is that we will be able to enroll that study starting next year. It is a very exciting opportunity where you've got 7,000- 10,000 patients in the U.S., and similar numbers abroad that currently have no disease-modifying therapies available. We're looking forward to hopefully replicating our phase one/two results that were very promising for being able to reduce total homocysteine levels. We're excited to share more on that later this year.
It is definitely going to be an exciting time over the next few months from a regulatory standpoint for both IgA nephropathy and FSGS. We stay tuned and are very excited. Thank you again for joining us.
Very good. Thank you for having me.