Great. Thank you very much for joining us today. My name is Mohit Bansal, and this is the post-lunch session. So we have an exciting company here with us. And I'm also joined by my colleague, Sadia Rahman, as well as on the stage. And we have Travere Therapeutics, Eric Dube, President and CEO of the company, and Peter Heerma, the Chief Commercial Officer of the company. Thank you, Eric and Peter, for joining us today.
Thank you for hosting us.
Awesome. So I have Sadia for all the tough questions here as well. So I'll kick off. So Eric, if you remember, I always ask this question every time, like, what would make you feel good about the year next year? And now we are a year after that conversation. So if you look back at the year, what do you think your key accomplishments were, and what is the investment case going forward on that?
I have to say I'm incredibly proud of my team for the accomplishments year to date. Since we had this conversation last year, we, of course, launched for full approval in IgA nephropathy with an incredibly strong uptake that continues. We had our strongest quarter to date last quarter. Just as that space becomes filled with many other treatment options, physicians continue to build a strong perception and use of Filspari. I think that that takes a tremendous amount of effort and great data. I'm very proud of my team with that. We've made very good progress on continuing to build a strong profile of Filspari in IgA nephropathy.
Last week's FDA approval for REMS modification, removing the REMS for pregnancy testing for embryo-fetal toxicity, and simplifying the REMS for liver monitoring from monthly in the first year to quarterly makes it just that much easier for patients and aligns their treatment or their monitoring schedule to how they often see their nephrologist. So that took a tremendous amount of effort to make sure that we're doing that and continuing to build easy access for patients with IgA nephropathy. And of course, we now have an accepted sNDA for FSGS. This is a community that we have worked very closely with over the last 10 years. We know many of their stories, and we know that this is a community that's really desperate for a therapy that's going to work for them and that is approved for their condition.
So we are excited about the work that we're doing there, and we're engaging with FDA along their review in anticipation of an approval on our PDUFA date of January 13 next year. So hopefully, next year's conversation becomes even more exciting with that potential approval. And I think those were the main areas of focus that I mentioned for last year.
Awesome. So yeah, quite a lot to discuss here. So I think starting with IgA nephropathy launch and, I mean, uptake so far, it's like every quarter we think that this is probably the highest new patient starts we'll see. And then you have been outdoing those. So can you talk a little bit about how you are finding these patients, where you are finding these patients, and in what inning you are in terms of finding those patients?
Yeah, thanks, Mohit. First of all, to Eric's point, very pleased with the continued performance. Second quarter that we disclosed a few weeks ago was the strongest quarter we had so far. Basically, I would say I see the launch of Filspari in two phases. The first phase was the accelerated approval. Then since September, since we had the full approval, we saw a meaningful growth of about 40% in our demand uptake. We've been quite consistent in generating new patient start forms of around 700 since Q4 last year, which was the first quarter after full approval. With regards to the dynamics, what you're asking for, like where are the patients coming from, we see a nice continuation of new prescribers coming into the mix. We also see a good amount of repeat prescriptions of experienced prescribers.
I think that's exactly where you want to be in about two and a half years into the launch because it speaks to the positive experience that physicians have, but also that the patients have. The compliance and persistence of Filspari is really high. And we start to see that also physicians are feeling comfortable to prescribe to patients with increased proteinuria levels, but maybe not as high as 1.5 or higher. So we believe that that's where the majority of the patient population is. About 70% of the patient population has increased proteinuria below 1.5. This is exactly the segment we are moving into. And I think the REMS modification that you mentioned earlier will help us to further occupy that particular space.
Can you elaborate on the drivers of the recent jump in PSF and why PSF growth recently outpaced revenue growth in past quarters? And can we expect more momentum in revenue growth going forward?
Yeah, it's a great question. You saw indeed a much stronger revenue growth in Q2 relative to patient start forms. It also speaks to what I mentioned earlier. Since September, we had the full approval. So you start to have prescriptions of patient start forms coming in that was maybe below the initial label. The initial label was in accelerated approval, kind of like the first phase that I was describing. Our label was basically for patients with proteinuria levels of 1.5 or greater. After full approval, there's no threshold for proteinuria. So basically, all patients at risk of progression in IgA nephropathy qualified for prescription, but that always lags a little bit from a payer perspective because the payer may not have updated their authorization criteria.
And so that lag is what you kind of like saw in the second quarter, that you had like that uplift that we saw in Q4 is now kind of like translated into revenue in Q2.
The only other thing that I would add is just on a gross-to-net standpoint. In quarter one, you often will see insurance resets, and that's often the quarter with the highest gross-to-net of the year. But that starts to moderate starting in Q2. And so I think that also contributed to what seemed to be a very strong quarter, and I'll cover in terms of the outlook, well, we've not provided guidance just yet, and it's still a bit early when we look at companies in terms of when they start to provide guidance in their launch. We do expect continued growth in our revenues moving forward for the reasons Peter mentioned. We have a very strong compliance persistence with the patients that we reach based on the great clinical profile, but also the support services that we provide.
With the continued reach of patients with patient start forms, that just allows us to continue to grow those revenues. If you look at the cumulative number of patients that we've been able to reach, we're not even at 10% of the full addressable population. We really do see that there are so many other patients that could benefit from upgrading from off-label RAS inhibitors to something that is superior like Filspari.
I guess on the point about payers removing restrictions, have most payers removed those 1.5 threshold restrictions? And are you seeing differences in how payers are covering attrition at this point with their accelerated approval?
Yeah, I'm very pleased with the continuation of updates of payers with regards to our full approval. And to the point that you're making, there's a new kid in town since four or five months now, atrasentan, that was introduced in the market. They're still in accelerated approval, a more limited label, 1.5 and greater. Plus, Filspari has the long-term benefit. And I think from a payer perspective, what is a payer looking for? Well, one, the highest rigor of evidence. Filspari has that with a head-to-head trial for a maximally dosed active competitor, plus the long-term data. And we price for broad access. So that allowed for a very strong inclusion in formularies and payer plans. And atrasentan is early in the stage. So I think we have a very strong position in payer plans for Filspari.
On compliance and persistence, you've highlighted strong compliance and persistence compared with other rare disease launches. Can you elaborate on that and any shift you expect now with reduced monitoring?
Yeah, I would say for other rare disease launches, but I would say in general, the compliance and persistence for a non-symptomatic chronic disease, what we have seen so far is as high as it gets. I think we are really exceeding any expectations that I had initially. I think to Eric's earlier point, it speaks to, one, the efficacy of the product and the safety profile, but also patients feel encouraged to take it because they see it works. For the first time, they feel they are winning against their disease and actually can stop another medication, their RAS inhibitor. So the compliance and persistence remains very high. I think it's part of the efficacy of the product, but it's also the support services that we are providing to those patients.
Can you talk a little bit about the REMS? So now that REMS has... So when I look at Filspari versus atrasentan, I mean, they are like... You have two mechanisms. They have one mechanism. You have an advantage of first mover, but the only benefit they have is probably at this point the REMS benefit. How you are seeing that in the marketplace and now with the newly updated label, where do you see comparative positioning?
Yeah, I think the REMS modification. I see two main opportunities. One is what I mentioned earlier with the change of the labels in September and the full approval with no proteinuria threshold. You see that we are moving. The median proteinuria level is actually below 1.5 and continues to move to the left, meaning lower proteinuria. So you get to a patient population that may not be monitored on a monthly basis, but all those patients basically are seen by the nephrologist every quarter. As part of the routine, the physician is always asking for lab values before the visit. So this fits very nicely within the routine of nephrologist by doing lab values every quarter. So I think it allows to occupy that broader patient population without additional obligations of monitoring. The second aspect to your point is the competitiveness because I think you're right.
Atrasentan has been really focused on their REMS as their core differentiator. I think with a quarterly REMS consistent to what is the general routine for those patients, the REMS obligation is really like a quarterly attestation of the patient that has done the lab value. So there's nothing more to that from a physician perspective.
Got it. And I think we discussed yesterday, I mean, you talked about potential to remove these REMS. So can you talk a little bit about how do you see what could the path look like in timelines?
Yeah, so we've had those discussions with the FDA over the last two years since we received accelerated approval and their decision to label us with a REMS. And they said that with additional data, they would reconsider the need for a REMS. Obviously, we now have seen that with the modification for liver monitoring and the removal of the pregnancy testing REMS for embryo -fetal toxicity. We've always had a two-step process. The first was to modify it to be better aligned to the frequency of visits for patients. And the second step would be full removal. That full removal really requires additional exposure data. Our post-marketing requirement is 3,000 patients exposed for two years. We've made good progress on that. And we'll continue to have discussions with FDA about when the right time for us to be able to submit an sNDA for full removal.
But we do see that that is a potential for the future.
Got it. So it's the timeline. Can you talk about timelines? I mean, or do you have?
Roughly, we've not provided specific timelines on that, but what we have said is that we would be looking to submit that after our PDUFA date for FSGS. We would not want to submit an sNDA that could potentially slow or delay our PDUFA date for FSGS. This is something that we would look to engage with the FDA to have the conversation about submission perhaps next year.
Got it. Very helpful.
Yeah, just on the IgAN launch, can you talk about the prescriber base for Filspari currently and how that's been evolving as the launch progresses? Are you reaching a lot of community physicians? And what's your strategy to compete effectively with Novartis?
Yeah. So let me answer it in two ways. First, on the prescriber base, the vast majority of the patients are actually being seen by their community nephrologist. So over 70% of the patients are being managed by community nephrologist. I feel that we have a strong position there. We have had a strong position, and I think we are certainly competitive there. With regards to your second question, like how do you compete against the new kid in town? I think atrasentan is the only direct competitor in the positioning of Filspari. But I feel very confident in the profile that we have for Filspari, given that it's a different mode of action. It's a dual inhibitor that inhibits both bad actors in the kidney that are exacerbating damage in the kidney, being angiotensin as well as endothelin.
You want to have the consistency of inhibition of both to really have consistent nephroprotection. The second part is the superior data that we have versus the maximal tolerated dosed active competitor with the long-term kidney preservation data as well. That's something that atrasentan doesn't have. Then the third one is the ease of access, the strong position we have in payer plans. That proposition resonates very well with physicians. Consistency of nephroprotection, long-term benefit, and ease of access with strong payer access.
And then the clinical guidelines. I mean, I think we are expecting them to be finalized later this year. So how do you think there was a draft guideline, but now with the final guideline, do you see a further inflection in new patients who are lower than one?
Yeah, I think I was really excited about the draft KDIGO guidelines that was basically disclosed the week before we got the full approval. I think KDIGO, the Global Guideline Committee, recognized that this is a disease that requires much earlier intervention and much more aggressive intervention. And they basically lowered that treatment target from 1 gram per day to 0.5 or preferably 0.3 grams per day, meaning complete remission. So basically what they're saying, every patient on IgA nephropathy that is not in complete remission should be a target for Filspari. So that's number one. Number two, I think they also articulate very clearly that there are two treatment categories for this disease. And when I spoke with Jürgen Floege, who is the chair of the KDIGO guidelines, what he was mentioning is like if I talk to my patients, I often tell them like, "You have two diseases.
You have a kidney disease, and you have an immune-mediated disease. And we need to target both." That's exactly how the KDIGO guideline is being written as well. You need a treatment that is targeting the kidney to protect the remaining nephrons, so a nephroprotective treatment, and you need a treatment that is immunosuppressive, and so that positioning, I think, is really important, so that's number two. The third one is the way Filspari is being articulated in the guidelines as the only medicine that has shown superiority versus a maximal tolerated RAS inhibitor and active control competitor. I think those three concepts will remain in the final guidelines as well. We have to see how that materializes. We anticipate that in the fall, it will be published. The opportunity for us is to educate the broader community on that.
I think the thought leaders are quite familiar with KDIGO, but I think in the community, there is still an opportunity to educate nephrologists on those three aspects that I just highlighted.
Got it. So since you talked about nephroprotection as well as the immune portion of the kidney disease, that could probably bode well for B-cell therapies, right? Because your drug is nephroprotective plus B-cell. So do you see a combination approach there over time, especially with the KDIGO guidelines asking for lower is better?
Well, that's exactly right. I mean, to the last point that you make, if you have more rigorous treatment targets, and if you go from one to preferably 0.3, that means that you go three times as low. The probability that you get there with one mechanism of action may be less likely. So you will see more combination therapies. That's why Filspari, we position it as foundational, start by protecting the remaining nephrons, see where you get. We have actually the strongest data with regards to complete remission. I think that's very well appreciated by nephrologists. But if you may not get there, you could add other mechanisms on top of Filspari.
Got it. I mean, so at this point, you do not think B-cells will become the first-line therapy for now, or at least from your conversation with the doctors?
Yeah, to the point that I'm making, I think you need to act on both parts of the disease. Nephroprotection, especially keep in mind when a patient is being referred to the nephrologist, over 75% of the patients have already lost half of their kidney function. Kidney loss is irreversible, so a nephrologist, the main thing they want to do is protect the remaining nephrons, and so that's why Filspari was positioned as foundational. Immune suppression is important as well, but you have to do both at the same time.
Got it. And the draft guidelines, well, let's see where the final ones come out this year, recommend that any patient that is diagnosed with IgAN that has proteinuria really needs to be on a combination for both of those categories. I think that gives the patient the best opportunity to stave off or slow the progression to kidney failure because the data is clear. Every patient in their lifetime with IgAN will face kidney failure if they have proteinuria. So we have the opportunity now with this innovation across these classes to be able to prevent that.
I think there's very strong rationale for combining these classes, but how do you think payers will implement or look at combinations given these will be high-priced drugs?
You want to take that?
Yeah, absolutely. Well, I think to my earlier point, I think there are three aspects that the payer is looking at. Like one, what is the price level? And we anticipated Filspari to be foundational treatment, but there would be more competition as well and potential combination therapy. So we priced Filspari for broad access. I think that's one component. The second one is the rigor of evidence. The payer is very keen on the highest rigor of evidence. And the highest rigor is head-to-head trial versus a maximally dosed competitor. We have that data. And then the third component is the long-term evidence. Is the drug providing the long-term protection to the kidney? That's what we have shown as well.
New medicine coming to the market, and you were referring to the APRIL compounds. Initially there will be under accelerated approval, more limited data, no long-term data in their phase 3 trial, and no head-to-head data. So I think that's a very important aspect from a payer in how they are evaluating the different treatments. And I think we have a very strong position based on those three aspects.
Yeah. I think it's also important to keep in mind that all of those trials are being done on top of foundational therapy and nephroprotection, so mostly RAS inhibitors, some including endothelin receptor antagonists like Filspari. So payers will be looking at the trial design and the inclusion criteria, and those medicines are being used on top of those therapies.
Yeah. Do you have any plans to generate additional data, like more robust data sets with combinations with Filspari with newer agents? Or do you think physicians will be comfortable prescribing these in combination at this point?
I think the first answer is yes, we are eager. We believe that we are leaders in this space. Leaders really invest in generating evidence that answers the questions of physicians, not just of regulators. If you look at the data set that we have generated, we're really, I think, paving the way for how you understand not just Filspari, but also this disease. We have the only trial that's been conducted head-to-head, as Peter talked about, to demonstrate why a physician should use Filspari over RAS inhibitors. We have the only trial that's done in treatment-naive patients where we're looking at what is the benefit of starting with a more robust therapy to start, and then we repeat biopsy to understand not just what's going on with their eGFR and their proteinuria, but what's going on in the kidney.
We've also done two studies in combination with SGLT2s. We have data on top of steroids in our phase three program. And we've also just recently initiated a program looking at recurrent disease in post-transplant, which is one of the highest areas of unmet need within the rare kidney space. So we're really proud of the work that we're doing to answer the questions that nephrologists have. And we welcome the opportunity to collaborate with those companies that have B-cell therapies to be able to address some of those questions. We anticipate that that would occur after these medicines are approved, where they demonstrate their safety profile and have FDA approval. But we do know that this is one of the key questions that physicians will have. It may not stop. Physicians will likely use these in combination because the mechanisms are well understood.
But I think there still is value in generating the evidence around safety and benefit. And I think we really have answered quite a bit with our SGLT2 combination showing very clearly an additive benefit when you use Filspari on top of SGLT2, which is fantastic for patients.
Awesome. So let's just move to FSGS. So of course, you are in the discussions with the agency and under the review. So can you talk a little bit about how your conversations with the agency are going right now? And what are the outstanding questions at this point that the agency wants an answer to?
Sure. I'll characterize the engagement since we've submitted the sNDA as very consistent with the engagement that we had with FDA during our review of the sNDA for full approval in IgA nephropathy. The types of questions, the frequency of questions, the timing of that, very consistent with our experience, which has been quite reassuring. The questions that we get, I would frame in the context of the discussion that we had with the FDA during our Type C meeting before we submitted for this indication. That's the meeting in which we asked FDA whether they would be open to a submission using proteinuria.
In that discussion, they said that this review is going to very much focus on understanding the benefit of sparsentan and FSGS in the context of PARASOL, PARASOL being this independent public-private initiative to better understand what the endpoints should be for clinical development in FSGS.
Got it. So is that fair to say FDA buys into PARASOL? FDA understands PARASOL, the data that they have generated? And basically, they're trying to understand how your drug and their data fits into the PARASOL paradigm?
Yeah. I certainly don't want to speak for FDA, but we do know that FDA has been part of PARASOL. They were core members of this, including their reviewers as well as their statisticians. So I believe that they understand the implications of PARASOL and the procedures and the findings of PARASOL. How much that means in terms of their review of Filspari, I think, is separate. So PARASOL was very much around understanding endpoints in this disease. The conclusions from PARASOL were very clear, which is eGFR is very important to kidney disease. It's a measure of kidney function. It's just not a feasible endpoint in FSGS because it's a highly heterogeneous population. There's high variability even within an individual patient over time when you measure eGFR. When you look at the biology of FSGS, regardless of the subtype, there's a common podocytopathy.
There is a continual damage of the podocyte in the kidney, which is the main filtering cell that leads to progressive proteinuria, which led the committee to assess proteinuria as a validated surrogate endpoint in this disease, and what we saw from PARASOL is that when you can lower a patient with FSGS's proteinuria below certain thresholds, you're able to reduce their risk of kidney failure over seven years by over 85%-90%, which does help to validate that independent of eGFR, proteinuria levels can predict a patient's risk of kidney failure. We're seeing a very similar pattern in our clinical trial. What's important to keep in mind is that we did not donate any of our clinical trial data on sparsentan to PARASOL to maintain the independence of that as they develop an endpoint, so FDA may certainly understand and appreciate the endpoint.
Their job now with this review is to assess the robustness and consistency and the clinical benefit of our data, and what we believe and what we've heard from many of the top experts in the field is that we certainly do see a consistent and robust benefit on proteinuria, particularly compared to maximum dosed irbesartan, which we know is a nephroprotective agent.
Helpful. One question, I mean, given that the administration is new, so implications on the FDA, that question we get a lot. So you have had discussions with the agency before this new administration and then at least the overall administration, and then after the administration has changed as well. Have you seen any difference in their tone or questions about the filing at this point?
Our experience with the agency throughout this entire development, including recently with the new administration, has not changed. They've been consistent. And one of the things that we found reassuring is the feedback that they gave to another company in this space with a phase III program in FSGS was very consistent with regard to the use of proteinuria as an endpoint for approval. So we do believe that there's consistency. And our job is to make sure that we're answering their questions and providing the right data to ultimately get this approved in January.
Got it. One last question on FSGS. I mean, is there an overlap between IGAN and FSGS in terms of prescriber base, or would you have to actually expand beyond just IGAN?
Yeah, it's a very similar prescriber base. It's over 80%-90% overlap. The only prescriber that we haven't called upon is the pediatric nephrologist. It's about 1,000 in the U.S. But further on, basically the prescriber for IgA nephropathy is the same prescriber as for FSGS, which I think gives me confidence as well that we will see a rapid uptake in FSGS much faster than what I first anticipated in IgA nephropathy, given that you have the same prescriber base, the high unmet need, but also the product is well established in this prescriber base, high brand awareness, and many of the nephrologists already have the experience with Filspari.
Got it. I want to touch upon pegtibatinase as well. I mean, this is a program which doesn't get a lot of attention, but I think you presented some data. I think something came out this morning as well. So can you talk a little bit about your excitement around this program and the manufacturing part of it, which kind of pushed you back a little bit, but again, now you're going for commercial manufacturing? Just talk a little bit about that and why investors should be excited about it.
Sure. Well, we're really excited about the opportunity to serve the HCU community. This is classical homocystinuria, which is a genetic metabolic disease that affects about 7,000 to 10,000 patients in the U.S. and similar numbers of patients in Europe as well as in other parts of the world. This is a disease that for half of the patients, they are diagnosed at birth during newborn screening. And unfortunately, half of the patients are not diagnosed and go on to eat a normal protein-rich diet that then leads to a toxic accumulation of homocysteine. These patients then start to develop a constellation of symptoms, including cognitive deficits, bone malformation, lens dislocation in their eyes. And by the time they're a teenager, a quarter of them will have an ischemic event.
Before a patient reaches the age of 30, over half of them will have an ischemic event if they are left undiagnosed and untreated. The primary way of treating this disease is in a very restrictive diet, basically minimizing any of the protein you have in your diet and to have a supplement of medicalized protein, which tastes horrible and is costly for these families. Patients will be on betaine or vitamin B6, which can help some patients, but not all. You contrast that with pegtibatinase, which in our phase 1, 2 program, we had 100% of the patients respond and get below the clinical threshold, 50% of them below a threshold that would allow their physicians to really consider liberalizing their diet. We're really excited about the opportunity.
And the data we presented this morning was from our open-label extension of the cohort 6 dose, which is the dose we're bringing into phase III. That shows that maintenance of effect in that reduction in methionine as well as homocysteine with no new safety signals emerging. So really exciting profile that really meets the needs of not just physicians in maintaining the level of homocysteine, but also the needs of patients in maintaining that and allowing them to consider additional protein in their diet. So we did initiate our phase III last year. We paused enrollment because we saw some challenges when we went from commercial manufacturing scale or from clinical to commercial. We paused that. We are well underway to resolving that and are on track to reinitiate enrollment of our phase III next year. And so stay tuned for additional information and update on that.
But we're really excited about the potential to be the first disease-modifying therapy for the HCU community.
Got it. Very helpful. Thank you for this. So maybe coming to the last question, again, same question every year. Hope we are sitting here next year, you and me both. And then if I ask you the question, what would make you look back at the year and say it was a great year for us?
Yeah, I want to focus on one word that you said, and that's hope. There are tens of thousands of families that hope that there will be something for them, that hope that they will have a therapy for their child with FSGS, or that there would be a clinical trial or a therapy for their child with HCU. I've spoken to mothers that have multiple children in their family with HCU. I've had fathers cry in my arms, pleading with me to do everything we can to get sparsentan approved for FSGS. If we sit here next year, I think we will be in a world that offers a lot more hope to those families, not just in the promise of Filspari, but in actually having access to the first medicine for FSGS and certainly the first phase III program in HCU.
I think next year could be a really, really powerful year for the rare disease community.
The best. Thank you very much.
Thank you. Thank you.