Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome the CEO of Travere, Eric Dube, and Chief Commercial Officer, Peter Heerma, from Travere. We're gonna do fireside chat format. Thanks so much for joining us today. Maybe to start off, if you want to provide a one-minute intro to the company.
Sure. So Travere Therapeutics is focused exclusively on rare diseases. Our focus is on rare kidney disease and rare metabolic diseases. We are both commercial and late-stage development, and we last year received accelerated approval for sparsentan or Filspari, which is the first non-immunosuppressive therapy in IgA nephropathy, the most prevalent of the rare glomerular diseases. We also completed the only phase III trial ever conducted in the most severe of the rare glomerular diseases, FSGS or focal segmental glomerular sclerosis last year. While we did not meet on the confirmatory eGFR endpoint, there has been a real galvanization within the expert and the patient community to identify a potential path forward for Filspari, given the limited treatment options and development, as well as this being a landmark trial to really inform what should be the endpoints for that trial.
So we're really helping to lead, in many ways, a set of diseases that has been so understudied over the last few decades. And then we have in our pipeline, pegtibatinase, which is a pegylated enzyme replacement therapy for HCU, classical homocystinuria. That is in phase III, and this is a disease that is genetic in nature, and essentially, infants who are born with this genetic disease have a toxic accumulation of homocysteine that comes from their eating protein in their diet, which can lead to a number of unfortunate outcomes, including ischemic events. Half of these patients have ischemic events by the time they're in their twenties. They have cognitive, and psychiatric, and bone malformation, as well as, lens dislocation and eye problems.
So this is a patient community that really is desperate for something that really affects the underlying cause of their disease, and we're excited to bring pegtibatinase through the clinic in the next couple of years.
Got it. Yeah, it's a great intro to the company, and let's start off with Filspari and your launch in IgA nephropathy and progress to date. So based on the solid 500+ PSFs that you reported last quarter, and what you're seeing in second quarter on patient demand and reimbursement, how are you setting commercial expectations for Filspari for the rest of the year?
Well, I'll give a high-level overview, and Peter certainly can speak in greater detail to what we're seeing. You know, we truly believe that Filspari will become the new foundational therapy for the treatment of IgA nephropathy, and the first year really was about setting the foundation, given that this is a community and nephrologists that have not had many options, building that foundation to build this growth, which we fully expect moving forward. We're not in a position yet to provide guidance on revenue, but as we move forward and we get through the most important of the milestones coming up, full approval with the PDUFA date of September fifth of this year, you know, we'll be in a better position to do so.
But we certainly expect growth to come, and Peter can speak a bit more to those details.
Yeah, I would say overall, really solid growth. Eric was talking about the fundamentals from last year, really focused on demand generation, making sure there is a coverage, a willingness to cover from a payer perspective, and then also the fulfillment process and the early experience from patients and physicians. And what we are seeing is a continuation of growth, both from a demand perspective, quarter over quarter, we see more patient start forms coming in. That trend is continuing also for Q2. And from a revenue perspective, we really saw an inflection in Q4, and that trend has continued in Q1 and also for this month, we expect to have solid growth so.
Got it. Okay. Yeah, that's helpful around commercial. And can you give us a sense of how many PSFs converted and potentially bookend the number of patients that are on therapy? And what proportion of the patients are on free drug program pending reimbursement?
Yeah, maybe it's good to take one step away from that. I mean, overall, we had well, we reported close to 2000 patient start forms coming in launch to date at the end of Q1. But maybe it's good to provide a little bit of picture, like, well, what are the steps going through from patient start form until you have the fulfillment? The first step is the patient start form that is signed by the physician and the patient. Then you have the REMS certification process that has to be signed by the physician and the patient. Then you have the PA process, the prior authorization process, and sometimes the appeals. And then ultimately, there's dispensing at the pharmacy, and the pharmacy is making sure that the patient also has done the lab value testing that is required.
As you can imagine, you may lose some patients along the way, and so I think in general, I've been over 25 years in industry, 10%-20% losing patients at the end of the day is quite common. And when you look at retail nephrology product, it's actually 15%+. So if I look at that benchmark and I look at other rare disease benchmarks as well, I think that we are right where we need to be. I think I'm really pleased with the progress we see from a payer perspective. We have 95%+ patients that have a coverage to a pathway for coverage.
We see also the high level of claims approvals, and then ultimately, when the patient is on drug, we see very high compliance rates. So I would say overall, even though we haven't disclosed the amount of patients that are on drug, we see very solid progress on the conversion.
... Got it. Okay, it's helpful. And, one challenge or opportunity ahead of you, depending on how you look at it, is to replace standard of care, ACE and ARBs. What pushback do you hear from payers on this, and are they requiring step edits, and, what do you hear from doctors about this idea?
Yeah, I would say overall, from a payer perspective, I think both the coverage and amount, and I mentioned the 95% plus, as well as the quality of the criteria. I think the criteria are very well established. And to your point, like, is there step edits? Well, most of the plans do require like three months standard of care, being ACE inhibitors and ARBs. That's not a problem. You have to take in mind that over 90% of those patients are being treated with ACE inhibitors and ARBs, and over half of those patients do not get to the target levels of proteinuria. So that's also the reason why we see very strong claims approval rates for Filspari so far, because that's not really an issue for patients.
That's right. Maybe I can just add two other points, Maury. The first is that really the clinical evidence is and should be driving some of these decisions, both for physicians as well as payers. And this is really where I think we've taken a leadership position in some of the trial design that we've done. This is the only trial within the IgA nephropathy space that is a head-to-head trial against an active comparator, in this case, irbesartan at max dose. And so payers, you know, having worked directly with payers in a prior company, they're oftentimes asking for head-to-head data, but companies don't often provide that. We now have head-to-head data in one of the largest trials ever done in IgA nephropathy. That level of evidence is really important for payers.
The second thing is, we do hear from some nephrologists that they're looking to prescribe Filspari for patients that may be early in their disease and may have not been on an ACE or an ARB. And while 95% of patients that are diagnosed are already on an ACE or an ARB, often from their primary care provider, we are excited to be able to provide evidence from our sparsentan trial. It's the only trial done in IgA nephropathy in a treatment-naive population, where these patients have a profound improvement in their condition, with 80% reduction in proteinuria, two-thirds of them getting into complete remission and a stabilization of their eGFR. And so there really is, I think, an excitement amongst the nephrologist community to, to prescribe.
While this is a very small portion of the population, because most patients are more progressed in their disease, we do see that there are physicians that are prescribing and payers paying for that without having to go through an ACE or an ARB.
Got it. Really helpful, and interesting. And, it's a good segue as well. You had data recently at the ERA meeting, where you showed comparisons of two-year eGFR slope versus the UK RaDaR study and also the placebo arm of the Calliditas phase III study. The method's an indirect comparison, but do you expect these data to resonate with payers and be sufficient, or is there ongoing effort to collect real-world data comparing the pre-treatment period versus the post-treatment period?
Yeah, I would say, you know, it certainly are supportive. They are supportive analyses in, you know, what is the highest level of evidence, a head-to-head phase III program. You know, what we are being able to provide is what would Filspari's long-term benefit look like versus placebo, essentially, because all of the other trials that are being conducted in IgAN are against placebo. And so we wanted to be able to provide that level of evidence to answer that question of what is it versus placebo. You know, will payers be interested in it? Certainly, you know, there will be an interest, but it doesn't replace the need for very rigorous phase III data, which we already have. So I think it certainly will be informative.
Got it. Makes sense. And what are the dynamics you're seeing as it relates to switches from prior ACE or ARB treatments, and also switching from Tarpeyo -treated patients post their first course?
You want me to take that?
Yeah, happy to take that one. So I mean, it's an easy switch. I mean, you can stop ACE and ARBs like one day and start Filspari the next day, so there's no other requirements. With regards to the Tarpeyo question, I think it's good to realize this is a disease of two categories. And I just came back from the European Renal Association in Stockholm, a big conference, I would say the second biggest after ASN. And what came out very clearly is like, well, IgA nephropathy is a disease of basically two diseases. You treat kidney damage, and you treat like an immune-mediated disease.
When those patients show up in the nephrology practice, there is a reason why they were being referred to a nephrologist, and that's often like proteinuria. The first thing what the nephrologist is doing, nephrologist, is protecting the nephrons, the remaining nephrons, and protect the kidney further versus further damage. That's exactly what Filspari is doing. Historically, that's been done with ACE inhibitors and ARBs. In the 1990s, they were known for, like, renal protective properties. But Filspari, take in mind, it had like a factor of three proteinuria benefit in after nine months, 50% versus 15%. But in the two-year study, it was like a factor of 10. It was 45% versus 4%. So very strong nephroprotective properties. And then the second component to your question is more the immune mediation.
That's what Tarpeyo plays. So it's not like you replace one with the other. I think they have two, they play both a different role, and they, they also interact in a different part of the treatment cascade.
Got it. Yeah, that makes sense. What about switches from SGLT2 inhibitors? Do you see patients switch from that class of drugs, or is it mostly add-on use?
No, it's seen as complementary, and it's, like overall, SGLT2 has impressive outcome data. Nephrologists, in general, do not really understand how it works. And if you look at the proteinuria benefit, and that's the post hoc analysis that was done with DAPA in the DAPA-CKD study, actually, the proteinuria benefit was only 25%-30%, compared to 50% for Filspari. So it's complementary, and it's not like replacing.
Got it. You've talked about seeing more uptake in community versus academic settings. Can you talk more about what's driving this?
... Yeah, I wouldn't say that it's a better uptake. I mean, the vast majority of those patients reside in the community. But I wouldn't say that there's a faster uptake in the community versus academia. Academia is a smaller prescriber base, but I'm actually really pleased with what the uptake that we're seeing in academia as well, and I would say that the majority of the key opinion leaders are prescribing Filspari as well, in particular, after we disclosed the full two-year data set at ASN.
Got it. And, as the launch has progressed over several quarters now, what's been the physician and patient receptivity to, to REMS?
Yeah, it's an interesting question. I mean, from a physician perspective, it's an easy process. It's like a 2-3-minute certification process, and a physician can contextualize, like, why is there a REMS? What we saw initially, and that it was in particular in the first 120 days, where you cannot promote the product as part of the accelerated approval pathway, is that there was a pocket of patients that required additional education with regards to box warning and REMS. After we had the opportunity to communicate better with patients in patient-friendly materials and better instruct the nurse educators from Travere Total Care as well, we saw really an inflection, and that's what you also saw then in the revenue in Q4.
That continued in Q1, and now also in Q2. So overall, I think from a REMS perspective, for physicians, very easy, and I think at the patient side, we made really meaningful progress.
Maybe just one, one important anecdote to the impact for the REMS. You know, we certainly wanted to make sure that this was an easy experience 'cause we know that it can be a, a burden. What really surprised us from a positive side is how consistent the clinical feedback was from patients, because they're getting very regular labs, including their kidney function.
Yeah.
And what they're saying to us, unsolicited, is that they now, for the first time since they've been diagnosed, do they feel like they're winning against their IgA nephropathy because they're seeing such profound reductions in their proteinuria. And so this is part of the reason why we believe that, and the regular touch points, that the compliance rate is so high. Many of these patients are saying, "Please make sure I would do anything to stay on Filspari because it's the first time that I believe that I have a future ahead of me that I'm optimistic about.
Got it. Interesting. As the launch has progressed over a couple quarters now, well, actually, with the one-year post-launch, real-world safety data that you've submitted to FDA, can you comment on how do these data look in respect to safety data and LFTs included in the label?
Certainly. So as part of our requirement, we provide one-year safety update, but we also had the complete safety data from both the completion of the PROTECT trial, as well as the DUPLEX trial in FSGS at double the dose of the IgAN dose. So we now have a much more robust data set, and we still have seen no cases of drug-induced liver injury. And when we looked at the one-year safety update, we continue to see that those rates of AST, ALT elevation are low and consistent with what you would expect from an ARB or an ACE inhibitor. So we look forward to discussing the safety data during our sNDA review this year.
Got it. For the sNDA review, you've got the PDUFA date scheduled for September fifth. Checking the boxes, has FDA said anything about asking for an ad com, and is there any perspective you can share on how you think the review process could unfold?
So we have been very pleased with how that process has been going on. FDA very quickly started to engage in the review of this sNDA. Upon acceptance of the sNDA, FDA did indicate that this will be priority review, and we will not have an ad com. So we believe that the data package is straightforward, and, you know, the, the analyses of eGFR clearly demonstrate that when you take into account more patients on irbesartan stopped taking therapy because it wasn't working, or they had an increased rate of rescue steroid therapy, that it certainly explains, the, the difference in treatment effect for, that, endpoint.
Got it. And, for chronic slope versus total slope, the EMA is comfortable with using chronic slope, and this is supported by your alignment with EMA on the PROTECT two or PROTECT two-year eGFR primary endpoint. What are your latest thoughts on the likelihood that FDA is gonna adopt this as well?
Well, our assumption has always been that FDA, as they told us before we started the trial, that while they wanted to have total slope as the confirmatory endpoint, they were interested in looking at all measures of eGFR as sensitivity analyses because there is... You know, this was a relatively new endpoint for them, the slope. Their thinking certainly has evolved, and they said such publicly last year at ASN, where as we get more data and understanding, their thinking of how to measure eGFR has evolved, and they're moving away from total slope as the preferred.
What they really are looking for is a measure of eGFR that is well understood within clinical practice, so we believe that's likely change of eGFR over time, but also a measure and a benefit that shows accumulation of that eGFR benefit over time, which is precisely what we saw in PROTECT. At year one, we saw a treatment difference of about 1.6 over irbesartan. That benefit and that treatment effect grew to 3.7 milliliters per minute per year at two years, demonstrating that that persistent reduction in proteinuria is translating into a growing benefit over time on eGFR.
Got it. And what are your expectations for label changes with the full approval, and does the Tarpeyo full approval label set the benchmark, or can Filspari do better?
Well, I think, you know, we have to look at them as different. One is a steroid, which shows, I think in their label, says that there is an increase in eGFR for a short period of time, but that there's no benefit longer term, you know, because this is a shorter course of therapy. And as Peter mentioned, this is a very different target for treating the immune part of the disease, not the renal protective part. So for us, we're looking at, you know, being able to show that accumulation of benefit on eGFR long term, but we also do believe that the indication statement will expand, much like we saw with Tarpeyo, to be able to treat a broader set of patients.
Those are the two primary changes that we would expect in a label, which would increase the addressable population for us to be able to reach for these patients.
Got it. That makes sense. And Novartis, they had some data at ERA last month as well. It's important to note that the Novartis study was placebo-controlled versus PROTECT's active control versus irbesartan. What was your take on the Novartis atrisentan data, as it's gonna be a competitor eventually with the ERA?
Well, certainly because it is an ERA, we're not surprised that it worked. I think the real question is: how is it working? And as you say, the trial designs are very different, and when we have a head-to-head trial versus an active comparator versus placebo, there are two really important components that are distinct. The one is that we optimize patients before randomization, really to make sure that patients are optimized on that background therapy. You often don't do that for standards of care background therapy. The second is, during the course and conduct of the study, when you have an active control, you're actively looking at pill count to make sure that patients are compliant.
For background therapy, oftentimes you don't know that, and we do know from certain trials that background therapy compliance can be limited, which is why we might see, you know, variability in the control arm, proteinuria rates. That said, when we take a step back and we look at Filspari, you have a 50% reduction in proteinuria with one pill, versus a 38% reduction in proteinuria with two pills. We believe that the clinical profile and the ease of use with Filspari is really important. That said, I think having another entrant within the endothelin class to be able to ensure that nephrologists are educated around upgrading what has been the background foundational therapy of ACE ARB alone, will only serve to support Filspari and the growing component of that renal protective part of the treatment algorithm.
Understood. In the atrisentan data, was the absence of liver function tests and the adverse events of special interest, was that a surprise based on atrisentan being in the ERA drug class? Do you expect atrisentan is gonna end up with REMS requirement as well?
Well, we certainly can't speak for FDA and what they will, will do. We do know that that trial was started well before FDA indicated to us that we needed to have a REMS for liver monitoring. What I can only say is what FDA shared with us when they told us that they would give us a REMS, which is, this is unapproved under accelerated approval in a class that has a potential risk for liver damage. And while we've not seen any cases of liver damage with sparsentan, they said that, you know, under accelerated approval, your safety and efficacy package is not yet complete. And so we would assume that they would be consistent, but we're planning for any possibility to make sure that we can be competitive with Filspari.
Got it. And you mentioned the one pill with Filspari versus two pills with the atrisentan regimen. I guess based on your market research and doc feedback, how do you envision doctors will use atrisentan in practice, and how practical is it for doctors to titrate the ARB dose in the real-world setting while adding the ERA on top?
You take it?
Yeah, maybe to take that one. I mean, first of all, ACE inhibitors and ARBs are, you go to the maximal tolerated dose, and so it's not like tinkering up and down. You go to the maximal tolerated dose, and that's exactly what Filspari does because you have, like, over 99% receptor blockage for angiotensin. So, I think it's a moving, it's a moving field. You have new modalities that are being studied that may come to the market at some point in the next one or two years. And so I think nephrologists have multiple opportunities to add on, but they don't have an opportunity to replace, and Filspari is, I think, uniquely positioned to really be that foundational care.
The first thing that you do is protect the kidney and go to the most efficacious kidney protective drug that is Filspari, and then you have the options to add on in the immune-mediated space. I think that's how physicians look at it. That's the way we position it. And to Eric's point, you have also... There is a compliance play with one versus two pills, but there's also an efficacy play, 50% reduction versus 38% reduction. So I feel that we are really well set up for to be competitive versus Novartis, atrisentan. And also from a field force perspective, I think we have a competitive amount of people in the field to tell that story.
Got it. Makes sense. Wanna ask a couple more questions, especially with FSGS. You spent a lot of time analyzing the FSGS data from the Phase III. What new information have you collected versus external data, and what are key points investors need to know about what you're doing here in respect to just the strengths of the data and particular subgroups you're focused on?
Well, we remain confident in the profile of Filspari or sparsentan in FSGS, given the profound and consistent reduction in proteinuria. Keep in mind that FSGS is the most devastating of the rare glomerular diseases, and it's the most proteinuria. So to be able to have a 50% reduction and to be able to get three times the number of patients in complete remission versus the current standard of care, is profound for this patient community. They're looking for something like Filspari. What we're doing is continue to collect data from open label extension as well as natural history, but we're also allowing the FDA, EMA, and the academic community to conduct their analysis of identifying an endpoint that may be more appropriate for clinical development in FSGS this year. And we expect to have a consensus statement from that PARASOL group in October at ASN.
If that is supportive of another endpoint beyond eGFR, we certainly will look to FDA and hope to bring sparsentan into this patient community that is desperate for something for them.
Got it. We didn't talk about your HCU phase III, but maybe if you can highlight key specific milestones along the way that investors should be focused on. Then just for the company as a whole just key catalysts ahead that investors should be paying attention to.
Sure. Well, HCU, we are actively enrolling in phase III, as well as doing the additional preparation for commercialization and manufacturing scale-up. We expect to have top-line data from that in 2026, and we're on track for that. As we look forward, the next six months will be very important for the company with the PDUFA date for full approval in IgA nephropathy, September fifth; hearing from the PARASOL Group, a potential consensus statement on FSGS in at ASN this year. We recently received approval or conditional marketing authorization for Filspari and IgAN in Europe, and are excited to have our colleagues at CSL Vifor for launch later this summer.
We expect to continue to have a very strong launch as we continue to grow and look to outperform other rare renal launches with Peter's team's efforts.
Great. Thanks so much for joining us today.