Thank you, everyone, for joining us. My name is Jason Zemansky. I'm one of the mid-cap analysts here at B of A. This is our second day of our 2024 Healthcare Conference in Las Vegas. I'm pleased this morning to introduce Eric Dube, President and CEO of Travere, as well as Peter Heerma, Chief Commercial Officer, in what should be a very exciting and interesting conversation. Gentlemen, thank you for joining us.
Thank you for hosting us.
Well, perfect. Maybe just to start broadly, especially for those who may be somewhat new to the story, can you provide a brief background of the company with specifics on your work on IgA and nephropathy?
Sure. So, Travere is a rare disease company, and we have a medicine that we just brought into phase III, pegtibatinase, for the treatment of classical homocystinuria or HCU. We're very excited as this has been a significantly underserved rare disease, and pegtibatinase is the only medicine in clinical development. And we also have FILSPARI or sparsentan, which received accelerated approval for IgA nephropathy last year. IgA nephropathy is a rare glomerular disease that affects about 150,000 patients in the US. In fact, it's the most common of the rare glomerular diseases. These patients really have been underserved, been treated off-label with steroids and ACE inhibitors, which unfortunately many patients either don't respond or fail to respond over time.
These patients will typically face kidney failure within a matter of maybe 10-15 years. So we're very excited to be leaders in this space and offering FILSPARI as the only non-immunosuppressive therapy for the treatment of IgA nephropathy.
Interesting. And maybe if you could... I wanna push a little bit on why FILSPARI was such a breakthrough. I mean, where do the RAS inhibitors come up short?
Sure. Well, I mean, RAS inhibitors or ACEs and ARBs have been used for decades, and we've known for just about as long as that they are renal protective, and so they've played a very important role. But unfortunately, they're insufficient. As we've learned more about these rare kidney diseases, and particularly the damage that occurs within the kidney, that damage, and specifically to IgA nephropathy, where you have IgA that's deposited into the kidneys, that leads to a disease process of inflammation and scarring. But mechanistically, what happens is it overactivates angiotensin and endothelin in the kidney, and that is what really is causing much of the disease process and the progressive damage that occurs. And for these patients, how they typically present is with proteinuria that is progressive over time.
That proteinuria is associated with that overactivation, and so RAS inhibitors have been used to be able to help in addressing some of the proteinuria. About 90%-95% of patients with IgA nephropathy who are diagnosed are on an ACE inhibitor or ARB, but unfortunately, most of them don't get into complete remission, and so their disease continues to progress. This is why FILSPARI, as one molecule that is both a angiotensin and endothelin blocking, is a better way to be able to address this damage and ultimately help in preventing the progression to kidney failure.
Got it. Well, you know, you mentioned, launches underway, so maybe this one for Peter. You recently reported first quarter earnings, that included $20 million in FILSPARI sales. Now, that was up about 35% quarter-over-quarter. Where are we in the launch, and has it met your expectations? And, you know, kind of what should we look for for the rest of 2024?
Yeah, I would say overall, I think we are exactly where I was expecting to be right now, about 15 months into the launch. We know that nephrology is a relatively conservative audience, and it's also because there has been so little innovation in nephrology over the last 30-40 years. I mean, Eric was talking about ACE inhibitors and ARBs. They were introduced in the 1990s, and steroids were already used in the 1980s. So little innovation has come to this prescriber population. Taking that in mind, I'm really pleased with the progress we have made. There's clearly demand. We see quarter-over-quarter growth in new patient start forms, and we're making real progress as well in transforming them into paid prescriptions.
So overall, I'm really pleased with the progress that we're making across the board, demand perspective, payer perspective, as well as the fulfillment perspective.
Got it. And any challenges managing the REMS at this point, or has it gone smoothly?
No, I would say... I mean, the REMS process has two components. One component is the prescriber. That's a very easy process. Within two minutes, the physician is certifying that the physician has read the prescriber guide, understands the product. So that has been very smooth, a very rapid process. What we saw initially in the first, I would say 2-3 quarters, that was that there was a pocket of patients that required additional hand-holding, additional education, because they were not aware of the box warning and what the REMS program meant. It also had to do because it's accelerated approval, the first 120 days you cannot promote, so we couldn't have the patient-friendly materials.
So the measures that we took in place with having the patient-friendly materials, by reinstructing the nurse educators that from Travere TotalCare have the interaction with patients, we really saw an uptake there. And that's reflected also in the revenue that you saw in Q4 and now continuing in Q1.
Interesting. What do you think the biggest hurdle has been in kind of jumping the gun a little bit here, but you know, you mentioned accelerated approval. Obviously, FDA just accepted your sNDA for conversion into full approval. Is that gonna have a measurable impact on uptake, you think?
I think there is a couple of elements, too, to take into consideration. First, I think it's, it, it provides more confidence, because there is full approval, right? But second, we anticipate that the label will be broadening. Right now, it states that it's indicated for patients at a rapid path of progression, generally with a proteinuria level of 1.5 or higher. We anticipate that that will go away, similar to what the TARPEIO label is today. So broadening of the patient population, but I think that coincides then very nicely with the new KDIGO guideline, which is the global nephrology guidelines that we anticipate will also bring down the proteinuria target to 0.5.
I think those elements together really allows for a broadening of the addressable patient population, plus what I said earlier, it's a validation of the profile for physicians that are more maybe on the fence and say, like: "Well, I'm waiting. It's still accelerated approval. With full approval, I'm starting to prescribe." So I think there's definitely an inflection that I'm anticipating when we have full approval.
Great. I think Cameron from my team had a few questions. Cameron?
Yeah, thanks. I'm curious what fraction of your prescribers are currently in academic centers or centers of excellence. You know, overall, what does it take to get more community-based caregivers to administer FILSPARI?
Yeah, maybe to take that one. You have to realize this, due to the dynamics in nephrology, the majority of those patients are residing in the community. And what you—like, in rare disease, typically you have centers of excellence. You see that less in nephrology, especially in rare nephrology. Like, community physicians try to hold on to their patients for a longer period of time. So, the majority resides at the community center, and that's what we see reflected also in the prescription of FILSPARI.
Gotcha. And then in 1Q, you reported 511 new patient start forms, you know, representing a cumulative total of 2K. Can you put this into context for us? What does a patient journey look like here? You know, how difficult is it to get there, and what does conversion look like?
Yeah, I would say, excuse me. So a couple of things, like when a patient start form comes in, a couple of things need to happen. First of all, the physician need to sign the patient start form, as well as the patient. Then you have the REMS certification process that needs to be signed by the physician and the patient as well. Then it goes through the payer process, the prior authorization, sometimes the appeal process, and then ultimately, you get to the specialty pharmacy for dispensing the product. And that also includes attestation of the patient that the patient has done the lab values. As you can imagine, across those steps, you may lose some patients.
What we know from my experience, I've been in the industry for over 25 years, is that ten to twenty percent patients that don't fill at the end of the day is a common number, and in nephrology, we did, like, a specific retail nephrology assessment as well. It's 15% plus. So you lose some patients in the process, but where we are with the steps and the improvements that we made, I think we are right there. And then from a payer perspective, we have very strong coverage already. What I mentioned last week in the earnings call is that 95% of the US patients have a pathway to reimbursement, but it doesn't mean that all the patients get reimbursed product right away.
I mean, you are replacing a generic RAS inhibitor, ARBs. A payer is always incented to, to put hurdles. Overall, I'm really pleased with, like, the authorization criteria that we have and the formularies that we have, but not all patients get to get to pay product. But within the context and, and describing the process from a patient start form to ultimately dispensing, I think we made really good progress and efficiencies in that process.
Perfect. Thank you. And then one more here on the REMS. You know, is there a possibility of potentially amending it, and what does that look like?
Yeah, we certainly do believe that, and our belief is based on what FDA told us when they indicated that they will be granting a REMS during accelerated approval. What they indicated is that under accelerated approval, we don't have the full benefit or the safety database demonstrated, and so... But that they are open to discussing the, you know, changes or removal of the REMS and pointed to precedent within the endothelin class. We believe that the first opportunity to do this is during the sNDA review, where we do, you know, sit down with FDA and review the label. And that's exactly what we plan to do. There importantly, still have been no cases of drug-induced liver injury in the 10-year development plus of sparsentan.
You know, having a broader data package with no cases will be very important. You know, whether it is in the removal of the REMS or it's improving and simplifying it to make it easier for some of the patients, as Peter mentioned, we believe will be an important step forward, and we'll be looking to have those discussions through this process.
Yeah, I think that's a great segue here into FDA itself. I appreciate it's always a challenge trying to read into tone and body language, but at this point, the acceptance of the sNDA with priority review, plus at this point, is there any doubt that you're gonna have an AdC om? Is it an indication of support at FDA? Can we say that at this point?
Well, I would caution in speaking for the FDA. What I can say is that the FDA has been incredibly committed to innovation within the rare kidney space because there's just been so little, and that they've been very collaborative with our team in this moving forward. I'll also say that this sNDA and the data package for full approval is incredibly strong, both from an efficacy and from a safety profile. No changes in the safety profile when you went from a 9-month look to 2 years, but also the data package is very strong, and while the measure of eGFR and the primary endpoint was not significant, I think we and FDA certainly have acknowledged that our understanding of how best to measure kidney function is evolving because of studies like PROTECT.
When you take that into account, and what really what FDA is looking for, which is an accumulation of benefit on eGFR. Late last year, after the two-year data were published, FDA themselves said publicly that, you know, their thinking of eGFR is evolving... Our program was one of the earliest, and so they wanted to look at eGFR slope. But eGFR slope is not really used in clinical practice, and so what FDA said is, you know, their thinking is evolving, and what they want to see really is two things. One, benefit in the measure of eGFR that is well understood and used in clinical practice, or we can take eGFR slope off because I still haven't met a nephrologist that uses this to treat a patient.
Second, they want to see accumulation of benefit over time in kidney function, and that's exactly what we see with sparsentan in the PROTECT trial. For example, when you look at the change in eGFR versus active control irbesartan at one year, it's about a 1.7 milliliter per minute per year difference. That in and of itself is very clinically meaningful. When you go out to two years, it's 3.7 milliliter per minute per year. So that treatment effect continues to grow the longer you're on FILSPARI, and this is the only study comparing itself to active control, so a very robust finding. And so what it tells me is that, you know, one, starting patients on FILSPARI and keeping them there, you're gonna have potential for benefit.
But also starting FILSPARI earlier compared to ACE or ARB is going to be helping patients more.
Got it.
Yeah, and just adding one thing. I mean, the accumulation of benefit that Eric was talking about, I think a very important element of the two-year data is that after two years, you basically saw the continuation of decrease in proteinuria with FILSPARI.
Mm-hmm.
While with the active control, irbesartan, you lost two-thirds of the effect. That's very relevant because that means that long term, like, it's a marker of damage, right? Proteinuria. That means there is continuing damage in the kidney. That gives confidence for physicians also in the longer term, beyond two years, that you will start to see-
Mm-hmm
... that continuation of separation of kidney curve.
I wanted to ask on that. I mean, obviously, PROTECT, the—there was the disappointment, the setback regarding eGFR total slope, but you know, now that you have, I think, fairly good evidence that FDA is comfortable with the entire data package. What does that mean to a physician who looks at that data point versus kind of the body language, if you will, of regulators?
Well, I think part of this is gonna come down to what is in our label. That's going to be the basis upon which Peter's team and our medical affairs team will be able to educate nephrologists on the data. And I think part of this is gonna be, you know, imperative for us to continue to discuss, you know, the rigor of the trial design. Keep in mind, this is the only head-to-head trial that has been or is being conducted in this space, and it was one of the first. And this is rare disease. You oftentimes have to find and identify endpoints that are imperfect early on because you just don't have a strong literature upon which to design these, and that's exactly what we saw here.
But when you take a step back and look at the profound improvements in proteinuria that Peter mentioned, as well as how that translates not just into a benefit on eGFR versus, you know, the standard of care, RAS inhibitors, you also look at the numeric benefit in hard endpoints that we saw at 2 years. This is what's meaningful to patients, and this is what's meaningful to nephrologists, and this is what I think ultimately is gonna allow us to replace the inadequate role that ACEs and ARBs have played in the treatment of patients with IgAN for years.
Wonderful. Well, moving to actually the treatment paradigm itself in IgAN, it's evolving. Where do you think FILSPARI ultimately fits in? I mean, in a world of potential combinations, do you think the drug could ultimately be foundational?
So absolutely, yes. And in fact, that's what we're starting to hear quite a bit from the nephrology community. Now, if we take a step back and look at how these patients have been treated for decades, it's really in two components. The first is foundational therapy that really address the damage in the kidney. This is the role that ACEs and ARBs, and now for many patients, SGLT2s play. They're renal protective, and they work in the kidney. There's another target that has been used for decades, and that is to address the immune overactivation. And in IgA nephropathy, that's really where the damage comes from, and that's the role that steroids have played for years. Now, as we look forward, what's really exciting for IgA nephropathy is that we're gonna have better therapies to be able to address both of those.
What's going on in the kidney? We now know that FILSPARI provides a superior benefit versus standard of care, and with the potential for complement B-cell and better steroids, you're gonna be able to replace the role that traditional steroids have played. We do not see, nor do most nephrologists see, that those are competing. Those are complementary approaches that for most patients, in order for them to get to complete remission, you've got to have both. And in fact, that's what we believe the evolution of the treatment paradigm. In the best interest of patients, you want to get them to complete remission, you really have to have both. And in fact, when you look at all of the therapies that are in development now to address the immune overactivation and replace steroids, they're all being studied on top of foundational therapy.
And so we think that we have a unique role to play in improving foundational therapy and also as a non-immunosuppressive, but working complementary with anything else that comes to market to address and prevent further damage.
It makes complete sense, I think, on paper, but as you mentioned earlier, nephrologists are a conservative bunch. Obviously, the treatment paradigm hasn't changed much over the last several decades. You know, again, from a practical standpoint, what does it take to get them to change their prescribing habits? Is it guidelines? Is it FDA? Is it just getting out there into the conferences and whatnot? I mean, what does it take to overcome that barrier?
Yeah, I'll say, you know, a few words, and I'll have Peter share his view. It takes data, it takes guidelines, it takes full approval, and I think it takes clinical experience. And it also needs to be easy. And I think that's exactly what we see with FILSPARI in the strong data with the profile that we've seen thus far. And in fact, when you look at some of the data in the only trial done in a treatment-naive setting in IgA nephropathy, this is our SPARTAN trial, FILSPARI reduces proteinuria by 80%. It gets two-thirds of those patients. If you start with FILSPARI, two-thirds of them get into complete remission, and you see no change or stabilization of eGFR over time.
That really is, I think, what, what physicians are looking for, and it's one pill, it's oral, it's once a day, and it's non-immunosuppressive. So I think it starts with that and really replacing what they've been already comfortable doing, which is using RAS inhibition to address the damage in the kidney. So we think that that's really playing into how physicians already think about treating patients with IgA nephropathy.
Yeah.
Peter?
Yeah, the only thing I would want to add is like, it's typical market development. I mentioned earlier, in the last 30, 40 years, there has been no innovation in this patient population. So physicians have been treating in a certain way and also have a certain level of satisfaction with levels that they shouldn't be satisfied with. And what we did early on, and we started this like 3, 4 years ago, was like really building a registry to get a better understanding of the natural history of disease and how are those patients progressing actually in real life. I mean, if you read the textbooks like 5 or 10 years ago, IgA nephropathy was being discussed as like a generally slower progressive disease.
Well, if you look at the data, the longitudinal data of patients following them, the majority of those patients will be on dialysis within 10 years. You have to realize this is a younger patient population. Many of those patients are being diagnosed in their early 20s. That means that you have patients ending up on kidney failure or dialysis in their 30s, 40s, sometimes 50s. So now I think you start to see like a whole wave of innovation. The market is being developed. Guidelines will follow, to your point, and that's why we anticipate also the treatment targets will go down.
But the noise, I think from us together with others, and I think we are really the leaders and the front runners in this field, will allow for more aggressive treatment more early on, and likely combination therapy with some of the new modalities that may come out as well. But I think in the grand scheme of things, to Eric's earlier point, it's a two-step approach. First thing you do, nephroprotective foundational medicine to address the damage in the kidney, and that's why patients show up in the nephrology office in the first place. It's good to realize, like, proteinuria is the main reason patients are being referred to the nephrologist. The first thing a nephrologist is doing is RAS inhibition, even before the biopsy is done.
That's where we play, that's what we replace, because FILSPARI has that RAS inhibition component, but adds the endothelin part, and that together allows for the magnitude of benefit that we saw.
Great. Maybe just a quick follow-up here. What does it take to get FILSPARI earlier in treatment? Is this an opportunity where combinations can be your friend by, you know, maybe pairing with an SGLT2?
Yeah, I think, I think that's gonna be critical. I mean, what really physicians are looking for early on, and what we've heard from them in a lot of the research that Peter's team has done, one, you want to have non-immunosuppressive. These are patients, particularly when you think about what they experienced during COVID, they want to be on a non-immunosuppressive therapy. Second, once-a-day oral with one pill is really important. So I think that that's gonna be, you know, something that is gonna be considered. Again, given that many of these patients are being seen in a community setting, these physicians are phenomenally busy, so to make it easy for them is important. But again, it's gonna be the clinical data.
We have two studies that are looking at FILSPARI in combination with SGLT2, and as I mentioned, our SPARTAN study, which is the only study currently looking at patients in a frontline setting, which shows profound improvements for these patients.
Great. Well, I certainly don't want to overlook this, but we recently got a first look at the data to be presented at ERA. What are your main takeaways here in some of the data that you can talk about that was in the abstracts?
Yeah, I mean, I think overall, what is really exciting is that this is a renaissance within the renal space, particularly within rare kidney diseases that have just been underserved. And, you know, we do expect to continue to lead in the data that we're generating. One of the things that really struck out to me was just how strong our positioning and our clinical profile is with FILSPARI, particularly the first look that we have of another endothelin receptor blocker, atrasentan, showing their interim data. And I think we have a very strong case for the benefit of dual blockade with FILSPARI. You know, if I were a patient looking side by side, you've got FILSPARI with 50% reduction at nine months in one pill, versus having to take two pills and you have a 38% reduction.
I know what I'd pick, and I think I know what the community nephrologists are gonna be thinking about when they think about the ease, but also the confidence that you have in the clinical experience you can expect with FILSPARI. But Peter, maybe you can share a bit more about what you think.
Well, I think you hit on all the points. I mean, it's an exciting time, first and foremost for patients, because patients didn't have any medicine that was approved for IgA nephropathy. Now you have to potentially have more in the future, so in different modalities. So I think that is great news. I think the profile of FILSPARI, I'm very confident in. I mean, 50% reduction in proteinuria, but we have seen none of the other compounds in phase 3 have shown that. It's all in the 35-38 range, including SGLT2. You mentioned SGLT2 earlier on. Promising data, but they had a proteinuria lowering effect of 25%-30%.
So it's, it's in combination, and I think with more aggressive treat line targets, I think it requires more combination therapy as well. And I think it comes back to Eric's earlier point, it's a two-prong approach. You wanna address the damage in the kidney, and you wanna go upstream in the immuno overactivation. That's the process moving forward, and you have different medicine in those two classes, but I think the profile that we have is very competitive. And next week at the European Renal Association conference, we will, we will see more of the data as well and discuss that.
Got it. Does that extend to, like, the BAFF/APRIL antagonists that are coming online? Again, you know, when you think about combination approaches and maybe FILSPARI thus far, you know, pretty superior profile.
Yeah, I would say the BAFF/ APRIL, very promising data so far, but it plays more into the immuno activation. So I think it's more competing with steroids. To Eric's earlier point, like, how long do you wanna suppress the immune system? Because that's what those drugs do. So I think it has probably a place if they will be approved, and again, this is phase two data that we're talking about. We haven't seen the phase three data yet. But it's in combination with... I mean, the studies are done on top of current standard of care, and the current standard of care is foundational therapy, RAS inhibition, and ARBs. That's where FILSPARI plays. So it's not like a winner takes all.
It's a two-step approach anyway, and those products are being used on top of FILSPARI's taking the space of ACE inhibitors and ARBs.
Great. Well, in the time we have left, I do wanna kinda cover what comes next. Obviously, you're looking to expand sparsentan into FSGS. What does this opportunity look like, and what were the lessons learned from DUPLEX?
Well, I think the opportunity really is to help give hope to the most difficult and severe of the rare glomerular diseases. These are patients that oftentimes are diagnosed as kids. I met a father and a patient at a rare kidney disease conference this weekend, whose son was diagnosed at 18 months. And when you see how rapidly progressing this disease is, and that there's very little in clinical development, this is a high unmet need. What we learned from the DUPLEX study is that FILSPARI has a very consistent and profound benefit on proteinuria. It's the most-- FSGS is the most proteinuria of the rare kidney diseases, and most patients that... and particularly those that we studied, are nephrotic in their proteinuria range. You were still able to get patients into-- There are 50% reduction in proteinuria.
One in five of these patients in DUPLEX were able to get into complete remission, three times greater than the current standard of care, ACE or ARB. While we did not achieve statistical significance on eGFR, I think the medical community and the FSGS treatment experts very quickly, in fact, within a matter of days after the New England Journal of Medicine published the DUPLEX trial, came together and said: "This is not about whether FILSPARI or sparsentan works in this disease, it's how we measure it." The treatment effect on eGFR versus active compared to irbesartan was actually quite similar between IgAN and FSGS. The variability in FSGS, in DUPLEX, was more than double, and that's because FSGS is a highly, highly variable and heterogeneous disease.
The experts, as well as regulators, now are looking at what is the right measure, what is the right endpoint longer term, to be able to prevent these patients from going into kidney failure? Because it is a matter of years to less than a decade, where many of these patients are gonna be facing kidney failure.
Great. We have about a minute left, but I did wanna give you some time to talk about HCU, and I apologize it's not much, but, what does the opportunity here look like?
Well, I mean, these are patients that have a rare metabolic disease that is genetic in origin, and they over time have a toxic accumulation of homocysteine based on their diet. Patients basically have to have a incredibly restrictive diet for protein because that's where you get much of the methionine and homocysteine. And so, these patients, you know, typically will face eye problems, skeletal problems, developmental problems, and perhaps most scarily, ischemic events in their teens and twenties. And so we really are looking to transform that with a pegylated human enzyme replacement. It's the only therapy in development and one that we believe will be, you know, disease-modifying for these patients.
There are about 10,000 patients that are addressable in the US and Europe, and we believe that pegtibatinase can offer, you know, a real change in how these patients manage their disease.
Well, exciting times. We'll look forward to those data when they come. Gentlemen, thank you so much for joining us.