Okay, welcome. Welcome to this fireside chat with Travere Therapeutics. I'm Joe Schwartz from the Biopharma Equity Research Team at Leerink Partners, and it's my pleasure to be hosting Eric Dube, President and CEO, and Peter Heerma, Chief Commercial Officer. Thank you very much for joining us.
Thank you for having us.
We can't help but notice all the progress, including today. Looks like you timed the filing for FILSPARI, the sNDA, to coordinate with our conference. Thank you for that auspicious contemporaneousness. Maybe we can just start by having you give us an overview of the key initiatives and priorities you have for this year before we dive into some more detailed questions.
Certainly. Well, our first priority this year is really to further establish FILSPARI within IgA nephropathy, and that really is a two-pronged approach. The first is certainly the continued launch progress. We ended last year very strongly and started this year also on a strong note. And then also then it is about our regulatory engagement. So the submission of the sNDA that we announced this morning puts us on track if we receive priority review for full approval later this year, which would expand our indication and help be a further driver of growth. One other aspect of this year, while not in our control but could be a significant driver for FILSPARI, is the KDIGO guidelines. It is a global guideline within kidney disease that should further support FILSPARI as a foundational therapy within IgA nephropathy.
The other priority that we have is helping to establish a regulatory pathway for sparsentan in FSGS. So that work is ongoing both within the company as well as independently through a public-private partnership called PARASOL with regulators. And then finally is the continued execution of our p hase III program, pegtibatinase, in classical homocystinuria and the continued manufacturing scale-up for clinical and for commercial.
Great. All right. So we saw really good growth in patients on drug last year, and it looks like, according to our calculations, you're at about 4% penetration already after just one year. And I'm wondering if you expect to see similar growth this year. Are there any takeaways from the traction you've been getting so far, and where do you see the launch going for this next phase?
Yeah, we've been very pleased with the growth in demand as well as further growth in revenue. We do expect that to be strong this year. Certainly, Peter can share a bit more detail on how that's going for the year.
Yeah, I'm certainly happy with the growth that we have seen in new patient start forms this year. I think FILSPARI is the first rare nephrology product that showed quarter-over-quarter growth. And to Eric's point, we ended the year strong, and we continue to see that momentum in the first quarter as well. I think ASN last year really helped where we had the full data set being presented as a late-breaker trial simultaneous with our Lancet publication that really sparked a momentum and an excitement for FILSPARI. And I think that's what we are building upon. And so far, I think Q1, we are up to a strong start of the year.
Okay. And you mentioned the KDIGO guidelines. Is that one of the biggest drivers, you think, that besides your own work building this market, do you think that that's one of the most important things we should look forward to in order to appreciate what could encourage more adoption?
Yeah, there are two elements of the KDIGO guidelines that we expect and are hearing from the community. And I'll have Peter speak about what the potential implications are commercially. The first is to be able to establish FILSPARI as a foundational therapy, really replacing what has been the longstanding role that ACEs and ARBs have played as standard of care within the treatment of IgA nephropathy. The second really is even more exciting from a longer-term perspective, and that is the potential to reduce the target for proteinuria from what has been 0.7 to 1 to potentially down to 0.5 based on a lot of the research that our teams have done with leading nephrologists, establishing that even patients that are at 0.5 and above, which have considered typically very mild and low risk, have a substantial risk of kidney failure within 10 years.
I think the entire community is really realizing that these patients that have been seen as low risk really need to be treated with better therapies and potentially more combinations. Those are the two aspects of the KDIGO guideline updates that we expect. Peter can talk about what that means commercially.
Yeah, so I think the first one, it's really positioning the product as we have it in mind. I mean, we see FILSPARI as foundational treatment that really works in the kidney. I mean, that's where damage is being done. That's where damage is being amplified, and you want to mitigate that and minimize that. So by blocking both angiotensin as well as endothelin, you have that effect in the kidney. And so that's why we see FILSPARI as replacing RAAS inhibition and really become foundational. We anticipate that the guideline will also describe FILSPARI as such. On the second component that Eric mentioned, the addressable patient population, we have set we anticipate the addressable patient population at launch is about 30,000-50,000 in the U.S. for IgA nephropathy.
We expect with the broadening of the label as well as a broader target or a lower target in the KDIGO guidelines, we anticipate that addressable patient population will grow to about 70,000.
Okay. And then in terms of the physicians who've been using FILSPARI to date, are there any appreciable patterns there amongst academics versus community docs?
Yeah, it's an interesting question. I mean, you have to realize that we target about 6,000 nephrologists out of a universe of about 10,000. According to our calculation, that covers about 85% of the patient population. And as you would expect, the majority of those physicians are in the community. And so that's where we see also a significant part of the uptake. But in the meantime, we also see a lot of academicians have come aboard, in particular after the full data set was being disclosed and published. And so the majority of thought leaders have now been prescribing FILSPARI.
Okay. And how are the PSFs translating to patients on commercial drug? Do you have a sense of what percentage ultimately are converted to a script? And how has that conversion rate been changing over time?
Yeah, maybe it's good to give you a little bit of context, like where we started a year ago when we launched and FILSPARI was approved through accelerated approval. That also means that you have a limitation how much you can communicate and how much you can promote in the first 120 days. Since we were past that in the summertime, you have more ability to have that communication to physicians but also to patients. I think that's an important one. I think most of the patients are on drug, to your question. But in the beginning, although the process worked for most of the patients, there was also a pocket of patients that needed additional education and communication with regards to the REMS program and the box warning.
In the first 120 days, the package insert was the only communication that we had. Now that we have more ability to have the communication with patients, we see that we have made quite some progress there. One of the lead indicators is how many patients you can get REMS certified in the first 14 days. We have seen really significant improvements there. And that means also that patients are transitioning to commercial shipments ultimately. And that's why you also saw the inflection that we saw in revenue in Q4 when we moved from $8 million - $15 million in Q4. And that's continuing as well. And that's what you would expect. First year is really about setting the foundation, getting into the formularies, making sure the payers are covering the product. And that's what we are seeing right now as well.
The coverage and the approval rates from payers are actually very high for FILSPARI.
How much of that growth was due to the data that you had at ASN? Do you think that can you quantify that for us in any way? Is there any way to contextualize that relative to the upcoming guideline inclusion?
Yeah, I would say the momentum was certainly there. As I mentioned, having the publication, there was a group of academicians that also saw that as the validation of the profile to start prescribing. As I mentioned, most of the thought leaders are prescribing FILSPARI right now. But there was really, I've been in industry for over 25 years. The intensity at our booth after the late-breaking session was really strong and better than I had seen in the past. It was a true interest in the product profile and how it can help patients ultimately. And so we saw also that translation in the numbers. And like I said, we built on that momentum in Q1. And so far, I'm really pleased for the outlook for this year based on that strong start of the year.
I think one other thing that I would add is not just the events of ASN or publication or the guidelines. One of the key things that we've seen, and when good launches go well, you see an impact of peer-to-peer engagement and peer-to-peer programs so that specialists are able to hear from others about the data and their clinical experience. And really, through the summer and into the back part of last year, we saw a real uptick in that type of execution by Peter's team that I believe is not just about having the publication out there or having ASN, but really having physicians, nephrologists, be able to speak to one another about their experience, the data, etc. And I think that that has been a key to our success and will continue to be moving forward.
Okay. That's helpful context. So in terms of the full approval label, we talked about the population that could be referenced on there. What about the REMS program? Is it possible for any of the REMS language to be changed at all through this process, or is that something that we might have to wait a little bit longer for?
Well, my hope for patients is that we don't have to wait because we don't see any signal of liver damage. We've not seen any cases. And so I think that it certainly warrants having a conversation with FDA. Last year, when FDA said that they were going to give us a REMS, they didn't indicate that with additional data that they would look to reevaluate the need. We see this sNDA and the additional data that will be in this and that we've collected both through the clinical programs as well as in real-world use, that it further supports a strong data package. Now, there is not precedent that we've seen in the removal of the REMS so quickly. So we want to be realistic. And we believe that even in an interim step, being able to simplify elements of the REMS could be quite helpful for certain patients.
But ultimately, we do believe that FDA could potentially remove the label or remove the REMS from the label. And we'll certainly take every opportunity we can with the additional data.
Okay. I guess taking a step back and broadly thinking about IgA nephropathy in terms of the overall landscape, how do you see this evolving over the next 5-10 years? I've heard you say a few times foundational therapy. It makes sense since this has a combination action with ARB included in it that you'd be a key component of that. But the development pipeline is getting a little bit more crowded, and there's some other agents that seem to have a pretty potent profile too. So what is your crystal ball?
Yeah. Well, I think I would say that our crystal ball 5 years ago has been slowly coming true. I mean, we've been talking about this as a renaissance within rare renal and particularly within IgA nephropathy as additional new classes of medicines are now in phase III. Our view is very aligned with how most of the thought leaders are thinking about the future as well. Keep in mind that nothing in IgA nephropathy is curative. And that means that you've got to have a long-term therapy to be able to do 2 things. The first is to address whatever injury is occurring within the kidney. Because once you start to see glycosylated IgA deposited in the kidney, there is a disease process that starts that leads to an overactivation of angiotensin and endothelin.
There's a crosstalk between both of those that you want to be able to tamp down because that does lead to inflammation and scarring that causes proteinuria. So proteinuria is the marker that shows that you do have injury in the kidney. So that's number one goal you want to address. The second goal is to be able to prevent further injury. And that's where there's some exciting new developments in the pipeline, whether it's B-cell or complement, replacing the traditional role that steroids have played in addressing that prevention aspect. So we believe that the foreseeable future in the treatment landscape is going to continue to be that address the injury in the kidney and prevent the injury in the immune system.
So what we see is the role of FILSPARI based on the superior profile we've seen going head-to-head against the prior standard of care should make FILSPARI the foundational therapy that addresses the kidney. For many patients, they'll be using SGLT2s as well because they've been demonstrated nephroprotective in CKD. And then there will be potentially other therapies that could be used on top of a foundational therapy. And that's largely how they're studied in phase III is using ARBs or complement inhibitors on top of standard of care, some of them including FILSPARI as foundational care. And so really, it's going to be about combination in being able to address the long-term goal of ideally a future where no patient with IgA nephropathy has to see kidney failure in their lifetime.
Okay. When do we get SGLT2 combo and frontline study data? And what do you hope to see there?
Yeah. So we have preliminary data that we presented last year. And we would expect to have additional data later this year at a medical conference. And when we look at the data we have thus far with SGLT2s, essentially, we show that there's no drug-drug interaction, that there is a safe profile to be able to use this in combination, which is priority number one for nephrologists because we are seeing many of these patients already on SGLT2 and FILSPARI. When we look at the frontline data from our SPARTAN study, this is perhaps one of the most innovative in the entire IgA nephropathy space because it's the first and only study that is actually looking at an incident population that is newly diagnosed and has not been on an ACE, an ARB, or a steroid.
And what we see when these patients are newly diagnosed and put onto FILSPARI, out to 36 weeks, you see a profound 80% reduction in proteinuria. Two-thirds of these patients are able to get into complete remission. And you see a complete stabilization of eGFR out to 36 weeks. Now, keep in mind, this is a very small study because it is an incident population that has repeat biopsy. So you can imagine that's not the easiest study to enroll. But what we've seen thus far has been incredibly exciting and I think reflects the foundational therapy but also the promise of what could be if a patient is diagnosed and intervened much earlier in their disease course.
So how realistic is it to think that there could be combination use in this field where there's so many new options being developed when we see that your agent seems to stabilize GFR? And I'm imagining that some other potent proteinuria reducers might be able to achieve that too. And so how do you think about whether or not that's realistic to expect?
Yeah. I think first, we have to keep in mind that the trials that we've seen thus far are in clinical trial setting. When we look at the real world and patients who are diagnosed when they already have injury in the kidney and they already have proteinuria, it signals that we could potentially have the opportunity with these newer classes of medicines coming to be able to not only address the injury in the kidney but prevent further injury. In order to achieve that, you have to have combination therapy. And we've known that all along. And this is why we've priced the way we did. We priced it for broad access. We priced it knowing that there could be other therapies to be added on.
Ultimately, when we look at what is going to be the best profile and outcome for these patients, there's no single agent that is going to be able to address that long-term from the data that we've seen or the clinical trial designs that we've seen thus far.
Yeah. Just adding to that, this is a dynamic market. And I mean, till two years ago, there was no approved therapies for IgA nephropathy. Because of the investment we made in working together with the RaDaR registry over 2,500 IgA nephropathy patients, we have a much better understanding of the trajectory of the disease. And this is actually a much more rapidly progressing disease than originally was thought of. That's what you see likely going to be reflected in the KDIGO guidelines with a lower target level for proteinuria. And so I think multiple modalities will help patients to get under that lower target level as well. So I think there is space for different products. But to Eric's point, the foundational treatment in the kidney, that is what has been the foundation with angiotensin inhibitors that will continue.
All the other modalities are being studied on top of angiotensin. FILSPARI blocks the angiotensin but also inhibits the endothelin part. I think that is an important component moving forward as well.
Okay. Interesting. So one more question on IgA nephropathy before we touch on FSGS and the pegtibatinase program. Oftentimes, when a new treatment or more than one comes to market, you see physician behavior change. And it seems like this is one where historically, physicians had to rely on biopsy or other methods to establish who's a high-risk patient and candidate for treatment. And we didn't have great treatments, but now we're starting to. So have you noticed physician behavior changing at all? And if you look into your crystal ball again for us, do you see any innovations in terms of diagnostics or other ways of identifying patients that could encourage the market to evolve and embrace all these new treatment options?
Yeah. I'm happy to kick that one off. So a couple of things. And I will answer your question with innovation in diagnosing patients as well. But I think overall, I mentioned there has been basically no innovation in the last 30-40 years. If you see the majority of patients are still being treated with generic RAAS inhibition and steroids, they've been around for 30, 40 years. ACE inhibitor 30 years ago, steroids 40 years ago. So for nephrologists to kind of adapt innovation is really it's a step-by-step approach. And when we launched the product last year, that's something that we spoke about as well. I've spent most of my career in nephrology. That is something what it takes to really educate the nephrology community.
Within that context, I'm really pleased with the progress that we have been making and where we are with FILSPARI today and also the outlook we have for the rest of the year. With regards to your specific question on biopsies, well, biopsies are there to stay because a payer is requiring biopsy to make sure that this is an IgA nephropathy patient and not, for example, a diabetic nephropathy patient, which is a much broader patient population. But there are new developments as well in, for example, a liquid biopsy for IgA nephropathy. And we have supported some of those initial research as well. And so eventually, the market may be moving there. But I think it's way too early for prime time for that particular.
Yeah. Very early. So biopsy will be the requirement, which I think, again, if you think about how this is diagnosed, it's through biopsy, which means there's already damage in the kidney, which is why I think a foundational therapy is going to be critical in the context of any other potential medicines that come to market.
Yep. Okay. That makes sense. So then moving to FSGS, where does this program stand? And what's the next update from you and/or the FDA?
Yeah. Well, I mean, this is a community that is desperate for a therapy. The number of parents that have come to me quite literally in tears pleading for us to continue to find something for their child is representative of the commitment that we have to FSGS. But I think it's also the commitment that the community and regulators have in finding a way forward. We, as we stand today, are much more optimistic in the outlook than we were perhaps this time last year. And that's because the academic community, the patient community, and regulators have come together in a public-private partnership called PARASOL to be able to establish a better endpoint for clinical development and regulatory approval.
I think based on the DUPLEX Study, which we completed last year, as the only phase III ever done in FSGS, there's clear recognition that eGFR in a 2-year period is incredibly difficult in this population because of the remitting, relapsing, and highly variable nature. So the community and regulators as PARASOL g roup have already agreed to move away from eGFR within a 2-year timeframe and to come up with a better endpoint, likely some measure of proteinuria. So we need to wait to see later this year. They're going to be meeting mid-year to be able to assess what are those options. And then we understand that it's their goal to be able to have a consensus statement at ASN in October with a potential for a new pathway. That allows us to be able to go back to the FDA, assuming that we have the data.
But we know that with regard to sparsentan, anything with proteinuria that we've seen has got a profound superiority over ACEs and ARBs. It then would be up to regulators to determine whether they would allow us to submit an sNDA with that additional analysis. So I think we've seen very good progress and a tremendous sense of urgency in the progress that we've seen within just a year's time.
Great. Okay. So moving to the HCU program, it was encouraging to see the phase III get underway with line of sight till 2026. So can you talk to us a little bit about how this is designed and how close you are to the patient community? And how do you feel about your ability to enroll the study?
Yeah. I mean, this is what I have to say. As a CEO of a rare disease company, these are some of the proudest moments that I've had where we are complemented by both regulators as well as members in the patient community for the innovative design that we've taken and the approach that we've taken in designing our HARMONY Phase III program. We know that regulators are going to want to know what is the improvement in total homocysteine. That's how these patients are monitored on a regular basis. And as we've seen from our phase II trial, an incredible and consistent reduction in total homocysteine, 100% response rate from these patients to be able to get below the clinical threshold. So that is going to be a core part. What I'm most excited about is what patients want.
They want to be able to introduce protein into their diet. These are profoundly restrictive diets that the diet in and of itself has negative consequences on their health. So we have, both before the patients enrolled in the double-blind, an extensive screening period to be able to standardize or stabilize the patient's diet over a 10-week period so that we minimize the variability that can occur if patients eat differently in the double-blind. We want to train them and stabilize that. After that 10 weeks, there's a 6-month double-blind period. And after that double-blind period, and perhaps what's the most interesting kind of attraction for patients is that they're able to then enter an open-label extension where we'll continue to follow these patients, but we also will be able to introduce in a protocolized way additional protein where we can measure this.
This is the first time that we believe that a company has done this to be able to standardize that. We look to be able to provide evidence both for FDA but even more importantly for the patient community that's just desperate to be able to have something that allows them to, in many ways, normalize their diet.
Yeah. That's interesting. So how does that work? And is there any way to describe that for us when you're standardizing the diet and then liberalizing the diet? What does that entail?
So keep in mind that this is going to be a global study. So to be able to standardize where everyone eats the same, that's not going to work. What we want to do is make sure that for whatever the patient is eating, you stick with that. And we want to make sure that the patient is sticking with whatever diet they have that is culturally relevant for them and what they're used to and that they have elevated homocysteine levels prior to randomization. We guide them to be able to maintain that same diet over the double-blind period. So that's essentially from screening to completion, 8-9 months.
And then once they roll into open-label extension, if they have levels of total homocysteine that are low enough and under a certain threshold that won't put the patient at risk, we would then, in stepwise fashion, allow them to introduce more and more protein into their diet so that we're able to look at how they are maintaining their homocysteine levels and also introducing more protein into their diet. And the mechanics of that, I think we've not yet provided publicly, but it is in alignment with investigators, with nutritionists, and with regulators to make sure that it's measurable and robust. And ultimately, we look to be able to provide those data to regulators as well. Which the total homocysteine, we have agreement to use as a biomarker for full approval.
Certainly, to be able to introduce diet is not just a patient-reported outcome but could be a clinically relevant one as well.
Okay. And how are these patients treated in the community currently? Do they have a treatment home, so to speak? And how much can you rely on existing referral patterns versus I remember with the FILSPARI FSGS program, you had to help the community to find where patients were and guide them to your sites that you wanted to be doing the study at. So where do we stand?
Yeah. Well, I'll cover it in two points, and then I'll have Peter close out with where he sees these patients being cared for. I think the first, in terms of identifying these patients, it's both in sites and experts that we see treat these metabolic disorders. But the other is through patient advocacy. So HCU Network America has done an amazing job over the number of years to be able to help in really creating the site much like we see for other rare disease patient support organizations. But Peter, maybe you can comment more about where these patients are treated.
Yeah. So we anticipate there is about 7,000-10,000 patients in the world that we think we will be growing as well. I think genetic disease is an important geneticist is an important call point ultimately. I think we have a good sense of where the patients are residing right now.
Great. All right. Well, thank you so much.