Good day, and welcome to the Travere Therapeutics Filspari FDA Full Approval Conference Call. Today's call is being recorded. At this time, I'd like to turn the conference over to Nivi Nehra, Vice President of Corporate Communications and Investor Relations. Please go ahead, Nivi.
Great. Thank you, Justin. Good afternoon, and thank you all for joining us today. Earlier today, we announced full FDA approval of Filspari. A copy of the press release, along with the slides that we'll be referencing on today's call, can be found on our corporate website. Today's call will be led by our President and Chief Executive Officer, Dr. Eric Dube. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer, and Peter Heerma, our Chief Commercial Officer, Dr. Bill Rote, Senior Vice President of Research and Development, and Chris Klein, our Chief Financial Officer, will join us for the Q&A session. Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 .
Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, September fifth, twenty twenty-four, and Travere specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, let me now turn the call over to Eric. Eric?
Thank you, Nivi, and good afternoon, everyone. Today's full approval of Filspari for the treatment of IgA nephropathy, or IgAN, marks a significant achievement for both Travere and the IgA nephropathy community. Our commitment to the rare kidney disease community began over a decade ago as one of the only companies at the time to embark on clinical development in RKD. Building on our work in RKD, our efforts in IgAN have been found in our core belief that patients living with IgAN remained at risk for kidney failure with historical standard of care, and that we could deliver a better foundational treatment. All patients with biopsy-confirmed IgAN show evidence of kidney damage, which often manifests as increased levels of proteinuria.
As the RADAR study now shows us, even patients with proteinuria as low as 0.5 g per day are at risk of kidney failure within 10 years. Approximately 90% of patients diagnosed with IgAN in the US have been treated with ACE inhibitors or ARBs as foundational therapy. Despite the widespread use of these kidney protective medicines, most patients fail to gain control, ideally, complete remission of their proteinuria and continue to progress towards kidney failure. This evolving landscape provides hope and a brighter future for the treatment of this disease. With full approval, Filspari is positioned to further expand its use as a superior foundational treatment relative to historical standard of care. You will hear from Jula how the long-term data from the phase III PROTECT study now further strengthens Filspari's profile, as well as how we expect the treatment landscape will evolve.
But first, I'd like to share with you the voice of patients who have been treated with Filspari to date. We regularly hear from people living with IgAN who are taking Filspari, and that they are relieved to have found a medicine that is working for them, that they are now better able to manage the complexities of living with IgAN, and that for the first time, they feel like they are winning against this disease. One young man shared his sentiment towards Filspari by conveying to us, quote, "When my disease first flared up, my protein was at 3.8 g. Now, after 10 months on Filspari, it is 0.45 g. I never thought I would be even close to normal. I've been diagnosed for 18 years, and we truly believe that on this last flare-up, it would be it for my kidneys." End quote.
While this is just one patient's experience and perspective, it highlights the impact that we are having on this community. Each story and each such connection with a patient continues to energize and inspire us to ensure that we are working as hard as we can to get patients who need Filspari access to this medicine. You will also hear from Peter about how the full approval of Filspari will help us reach more patients. At the highest level, there are four priorities for us at Travere to deliver growth in the next phase of the launch. One, educate nephrologists and patients about the superior long-term profile of Filspari that is now included in our label. Two, reach more patients by engaging with nephrologists who have not yet prescribed Filspari to their patients with IgAN.
Three, build upon our existing prescriber base to educate them on how to identify additional patients with IgAN who can benefit from upgrading their foundational therapy to Filspari. And four, expand access to new patients outside the U.S by working with our partners, CSL Vifor and Renalys. Before I turn the call over to Jula for her overview, I would like to express my deepest appreciation to the IgAN patient community, including their families and caregivers, the PROTECT investigators, and the team at Travere, who has executed with perseverance and a compassionate focus on what is best for patients. And now, I would like to turn the call over to Jula for her overview of the clinical importance of full approval. Jula?
Thank you, Eric. Let me also, first and foremost, add my gratitude to the entire IgAN community for inspiring and motivating us every day on this journey to reaching full approval for Filspari. Historically, IgA nephropathy was thought to be a relatively benign disease, but we now know that most IgAN patients will face kidney failure in their lifetime. As outlined in the recently released draft KDIGO guidelines, IgAN patients need to be diagnosed earlier and treated to a lower proteinuria target of close to complete remission in order to reduce their lifetime risk of kidney failure. Having served as a practicing nephrologist for over twenty years, treating IgAN patients with limited treatment options, I am thrilled for the IgAN community about the full approval of Filspari and its potential for slowing the course of progression for patients with IgA nephropathy.
As we highlight on slide seven of our deck, Filspari is unique in targeting the overactivation in the kidney by blocking two key pathways, endothelin-1 and angiotensin II, which work together to cause kidney injury in IgA nephropathy. As the only kidney-targeted medicine approved for IgAN, Filspari offers patients a simple once-daily oral, non-immunosuppressive treatment that can provide superior results and replace their RAS inhibitors. And most importantly, this full approval milestone enables Filspari to be positioned as a foundational treatment to preserve kidney function for patients with IgA nephropathy. This is consistent with what we hear from speakers and thought leaders on their views of the role of Filspari for treating their IgAN patients. Core to this belief is our now expanded label for Filspari, that we believe is a great outcome.
It is important to remember that PROTECT is the only phase III study conducted against an active comparator, which is outlined on slide eight. This is especially relevant because maximum-dose irbesartan, which was used as a comparator in our study, has demonstrated a statistically significant better response than optimized background RAS inhibitors, which was used as a placebo in other studies, as outlined on slide nine. Filspari still demonstrated superior results over maximum-dose irbesartan. I'll now walk through the updated label. Filspari's indication statement is now reflective of a broader patient population of IgAN patients and allows the physician to determine who is at risk for progression. We know from the RADAR data that even patients with proteinuria levels of close to 0.5 g per day have a one out of four risk of kidney failure within 10 years.
Accordingly, the recently updated draft KDIGO guidelines state that all patients with proteinuria greater than 0.5 g per day are at risk for progressive loss of kidney function and should be biopsied and treated. Our label also now includes more details around proteinuria reduction. Treatment with Filspari resulted in a rapid reduction in proteinuria, nearly 50% at 36 weeks, and the antiproteinuric effect is sustained over the study period. Importantly, the KDIGO guidelines have changed the treatment targets from 1 g per day to 0.5 g per day or 0.3 g per day to achieve near or complete remission. As shown on slide 10, we have published that nearly three times more patients achieved complete remission when treated with Filspari versus irbesartan.
This compelling complete remission data is also within the context of nearly three times more patients on irbesartan in the PROTECT study, requiring rescue immunosuppression therapy as compared to Filspari. These data are important for patients, as many want to avoid immunosuppression treatment and its associated side effects. The kidney function preservation data in our label outlines the ability for Filspari-treated patients to maintain significantly more kidney function over time, compared to treatment with maximally dosed irbesartan. Importantly, the benefit of Filspari on kidney function accrued year over year over the course of the 2-year measurement period. As highlighted on slide 11, we see that the absolute difference in kidney function based on eGFR with Filspari versus irbesartan is +1.9 mL per minute at 1 year, and this increases to +3.8 mL per minute at 2 years.
Filspari is the only approved medicine to demonstrate this effect in IgAN thus far. The analysis included in our label, preferred by the FDA, is the intention to treat analysis with imputation of data after a patient receives rescue medication or reached kidney failure. These results are consistent with what we have published in The Lancet and demonstrate a statistically significant and clinically meaningful effect on preservation of kidney function, based on a total slope difference of 1.2 mL/min per year. What this beneficial kidney function data translates into is shown on slide 12. If you extrapolate out the potential treatment effects, you can observe the theoretical benefit on avoidance of kidney failure for a patient who started Filspari with stage 3A kidney disease.
They could potentially add almost five years free of kidney failure and or dialysis to their life, compared to maximally dosed irbesartan. Our label also includes updated safety data. Importantly, there were no new safety findings, no cases of drug-induced liver injury, and an overall safety profile that supports the long-term use of Filspari as a foundational treatment. As we previously discussed, our full approval submission was the first natural juncture since accelerated approval to engage with the FDA regarding the potential modification to the liver monitoring REMS that is in place for Filspari. This process is independent of the review, involving multiple divisions of the FDA, and we are pleased to report that we have made progress with the process.
Per discussions with the FDA, in order for them to evaluate a potential REMS modification, we intend to submit an updated safety summary in an sNDA for a major REMS modification. We are engaging with the FDA to ensure alignment on the data package to support this submission and will then submit for a potential modification. We are proud of our full approval and updated label for Filspari, and we intend to present and publish new data to support the role of Filspari as a kidney-targeted medicine that can safely be used in combination with other medications in order to extend a patient's kidney life. As outlined in KDIGO, the treatment landscape is evolving to a two-pronged approach, treating the kidney injury and treating the immune overactivation simultaneously.
Filspari is the only approved IgAN medicine that directly addresses the kidney injury and is in position to replace RAS inhibitors as foundational care and potentially be used as a first-line treatment. In support of optimizing this foundational kidney-targeted medicine for IgAN patients, we will be presenting data at ASN on the combination of Filspari with SGLT2 inhibitors and with immunosuppressants. We also have additional data examining Filspari as an early treatment option for newly diagnosed RAS inhibitor-naive IgAN patients from the SPARTAN trial, and data in patients with lower ranges of proteinuria. The earlier SPARTAN data previously presented showed nearly two-thirds of the patients achieved complete remission with Filspari, and that kidney function remained stable out to nearly a year. In summary, the full approval of Filspari represents a significant milestone and new hope for patients with IgAN.
This approval also represents many years of commitment from patients and our advocacy partners, our investigators and collaborators, and our teams at Travere, who all contributed to this success and to whom we are immensely grateful. Let me now turn it over to Peter for a commercial update. Peter?
Thank you, Jula, and good afternoon, everyone. Filspari's full approval is an important milestone for the entire IgAN community and for our team at Travere. We couldn't be more excited about the opportunity ahead of us, building upon the strong foundation that we have established since our accelerated approval in February of last year. This full approval opens an exciting new chapter, allowing us to further accelerate Filspari's growth trajectory for two reasons. One, we can now leverage the full potential of Filspari in our physician communication and educational initiatives. Thus far, consistent to FDA regulations, we have been limited in our commercial communication efforts under accelerated approval.
But now, with this full approval, we can discuss how Filspari's rapid and sustained proteinuria reduction translates into superior long-term kidney function preservation relative to active comparator Irbesartan, and this kidney preservation benefit accrues year over year for two years, supporting long-term use of Filspari. And two, the new and compelling indication statement supports broader use of Filspari in all adult patients with IgAN who are at risk of progression. As a reminder, under accelerated approval, our indication statement guided physicians to use Filspari only in patients generally at or above one point five g per g. With the removal of the reference to a proteinuria threshold, we now have an opportunity to serve more patients with Filspari. In addition, as Jula mentioned, KDIGO released their new draft guidelines just last week, and I am particularly excited about these for three reasons.
One, the urgency to diagnose and treat patients earlier is amplified by the more ambitious treatment targets, aiming for proteinuria levels near remission. Two, optimal treatment of IgAN patients includes two treatment categories that should be used simultaneously. One targeting kidney injury and one targeting the overactivation of the immune system. This is critical, as Filspari is the only kidney-targeted medicine indicated for IgA nephropathy. And three, the guideline recommends Filspari as treatment options to target kidney injury, thereby positioning Filspari as a foundational treatment option that is more efficacious to ACE inhibitors and ARBs. It is important to realize that most patients are being diagnosed with significant kidney injury already. These patients can directly benefit from a more efficacious kidney-targeted therapy like Filspari.
With our new label and a goal to treat patients earlier in the draft KDIGO guidelines, we believe we have the potential to extend the addressable patient population from 30 to 50 thousand at accelerated approval to more than 70 thousand, and we expect this to further grow over time. Our teams are ready, passionate, and prepared to seize this opportunity to its full potential in serving more patients. Our first priority is to broaden our prescriber base by reaching nephrologists who have not yet prescribed Filspari to their IgAN patients. We have identified a segment of about 1,000 physicians who believe in this medicine, many who are already REMS-certified, but have been waiting for the validation of full approval to start prescribing. We plan to reach these physicians through targeted campaigns, professional meetings, and direct interaction with our field teams.
Simultaneously, we will focus on building upon the experience of our existing prescriber base. In daily practice, we have seen that IgA nephropathy treatment typically isn't adjusted until patients reach higher proteinuria levels. With a more ambitious treatment target in the draft guidelines and no longer a proteinuria threshold in our label, there is an opportunity to identify more IgAN patients who can benefit from upgrading their ACE and ARB therapy to the superior and foundational use of Filspari. To achieve this, we will be training our field teams to the new label and provide them with our newly developed campaigns, messages, and materials. This allows our field force to engage and educate nephrologists on the new indication statement and the superior long-term kidney preservation benefits of Filspari for their patients, with a safety profile similar to active comparator irbesartan.
Our national account directors will be educating payers about the new label and indication statements, Filspari's enhanced value story with superior long-term kidney preservation evidence, and the new draft KDIGO guidelines. This will allow for an opportunity to adjust payer plans and authorization criteria for reimbursement and broaden the eligible patient population that can benefit from Filspari. Often, IgA nephropathy patients are diagnosed in their early twenties and thirties, and at risk of kidney failure within ten years. For so many years, these patients had no treatment options indicated for their disease, and they have often been faced with the burden of taking multiple pills a day to try to take control over their IgAN. As you heard Eric say earlier, we continue to hear from patients that for the first time, that they feel they are winning with Filspari.
Patients can now replace their ACE and ARBs without adding a new medicine. This one pill, once a day, makes it easy to adhere and also seamlessly fit in their daily routines. This is reflected in the high compliance rates we are observing with Filspari. The future for treatment of IgAN is bright, and we are excited to play a pivotal role in establishing the new treatment foundation for IgAN patients and accelerating the growth potential of Filspari. We are on track to outperform benchmark recent rare nephrology launches in the second year of launch, and our teams are ready to seize this opportunity and serve the increasing patient population that can benefit from Filspari. Let me now turn the call over to Eric for his closing remarks. Eric?
Thank you, Peter. We are deeply humbled by everyone who helped us to reach this achievement, particularly considering the historical gap in development in RKD. Supporting the RKD community and providing hope has been a driving force for us at Travere. As our attention turns to reaching more patients with IgAN, we also remain committed to finding a path forward for the FSGS community. We are eagerly awaiting the output from the PARASOL group. In the meantime, our remit is clear, help patients with IgAN upgrade their foundational therapy. Now, let me turn the call over to Nivi for Q&A. Nivi?
Thank you, Eric. Justin, we can now open up the line for Q&A.
Thank you. If you would like to signal with a question, please press star one on your touchtone telephone. If you're joining us today using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. As a reminder, we ask that you limit yourself to one question. If you have another question, please rejoin the queue. We'll now take the first question from the line of Joe Schwartz with Leerink Partners. Joe Schwartz, your line is open.
Great, thanks so much, and congrats to the whole Travere team on a hard-fought win. So I'm just wondering if you can give us some insight into your discussion with the FDA on the REMS. How did that go? Who has weighed in already? Who still needs to weigh in, and what's the process there? And what's the most likely change to the REMS? Do you have a sense whether it's a relaxation, or could it actually be an entire removal?
Joe, thank you so much. And let me take the the question around the REMS. And I think it's it's very aligned with what we've said previously, which is that the full approval process that we just obviously went through was the first opportunity for us to engage the multiple divisions of FDA in request of modifying the REMS. We made really good progress with these engagements, and we've got some more work to do. Our intent is to submit an sNDA for modification, as Julie mentioned, and you know as is our practice, we don't provide commentary on those engagements or the details until we get through them. What I can say is that with the additional exposure data that we have to date, and still no cases of drug-induced liver injury, we remain confident on this path.
So, let me pause there and ask Bill if there's anything else that he would like to add on Joe's question.
I guess the only thing that I would add is that the agency guided us that this needed to be a separate submission. They wanted to keep it separate from the full approval process, and that as we engage with them more and we hit milestones, we'll be back and we'll update stakeholders at that point.
Yeah. Thanks, Bill. Joe, the only thing that I would add just on this topic, and it's not directly to your question, but we'll certainly provide, you know, more information as we progress along this path, is just a reminder to you and everyone that we have delivered very strong performance with this launch to date. And as we stated previously, you know, we plan for very strong growth regardless of how the REMS is treated with the full approval label. And we believe that based on the expanded indication statement, based on the draft KDIGO guidelines that now are in hand, and most importantly, the tens of thousands of patients with IgAN who deserve better, I am absolutely confident that we're gonna see strong growth moving forward.
Thank you.
Thanks, Joe.
The next question will come from Anupam Rama with J.P. Morgan.
Hey, guys! Thanks so much for taking the question. Just wanted to follow up on Joe's question a little bit on what are the timelines for submission of the sNDA for Filspari? And is this just kind of like a matter of repackaging data and some of the real-world evidence that you have on liver modeling, or something more expansive than that? Thanks so much.
Yeah, thanks for the question. Bill, why don't you take that one?
Yeah, I think. Thanks for the question, Anupam. The short answer is yes. With the expanding clinical trial data that we're generating with the open label extension and the expanding real-world data that comes through the commercial experience, the exposure database, as you can imagine, is growing quite significantly. And that provides us with, you know, a quantum of data that's sufficient to go back to the agency and present what we're seeing, which is no signal, and have that conversation with the agency. So we're in the process of aligning on just what that package needs to include, and once we have that, then we'll move rapidly toward a submission.
Just a clarification question, you will be working with KDIGO to ensure what kind of, like, the full product label language is now going to be reflected in sort of the final KDIGO guidelines? Thanks so much.
Great question, Anupam. Thank you. Jula, why don't you take that one?
Certainly. We are working with KDIGO. Since our data was already published in the Lancet, as you recall, last year, they have the vast majority of this information, so there would just be some minor adjustments. But to reiterate, we're very pleased with the KDIGO guidelines and where we're placed, demonstrating that we can preserve kidney function, we reduce proteinuria, and that we should be placed as a foundational treatment. So it's really just some minor adjustments, but be assured we're working with them.
Cool. Thanks again, and congrats.
Thank you.
Our next question will come from Carter Gould with Barclays.
Great. Good afternoon. Congrats to the team on the full approval. Maybe one for Peter and team. When you think about sort of the timeline by which payers will sort of maybe update policies on the back of the KDIGO guideline changes, you know, what's sort of the expectation, Peter, there? I know it's early days, but is that something that you expect to happen immediately, a more meaningful amount of time for, I guess, the bureaucracy to churn, or is this something that we should expect more around sort of with the turning of the calendar? Any commentary there would be helpful. Thank you.
... I'll take that one. Yeah, it depends on the payer policy, but rest assured, we have a very active national account team that is contacting payers basically directly now that we have the full approval. I feel very strong about this position that we're in. Just to give you the context, Filspari was studied in the most rigorous trial design, and I would say that we have the gold standard for the study design. Filspari was studied first as an uptitrated, maximally dosed active comparator. We have a strong value proposition now with the rapid and sustained proteinuria reduction that is now also having the evidence of kidney preservation that is accruing year-over-year versus an active comparator.
So I think we are in a very good spot to have conversations with the payers. And, I've been very pleased with the progress that we have been making, and I think we are in a strong position to update authorization criteria with the new label as well as with the new KDIGO guidelines.
Thank you. And the next question will come from Laura Chico with Wedbush Securities.
Good evening. Thanks very much for taking the question. I have one kind of related to the four priorities you mentioned, Eric, and bottleneck probably is not the right word, but at this point, commercially, is it more a matter of getting patients diagnosed, so naive to treatment, or is it more reaching the already diagnosed patients under care? I guess I'm trying to understand perhaps how many earlier-stage patients have already been identified but not necessarily prescribed Filspari. Hopefully, that makes sense. Thanks.
Yeah, Laura, really great question. Peter, do you want to take that?
Yeah, absolutely, Eric. And, Laura, I appreciate the question. I mean, what we have seen so far is that, and I made a statement in the prepared remarks as well, that the initial use for Filspari is often in the higher proteinuria ranges. And I think physicians have to get comfortable with that there is a higher urgency to treat those patients earlier and more aggressively. And I think that is the call to action that I see in the KDIGO guidelines. I think there is an opportunity to go to lower levels proteinuria. We have been talking about it. We were one of the sponsors for the RADAR data set to really get a better understanding what is really the risk of progression.
And as Jula stated today in her prepared remarks, even patients that are close to point five still have a one in four chance to progress to kidney failure in their life. So I think that is the call to action that we will further amplify to physicians. I think there is the group of patients out there that have been diagnosed, that have the confirmatory biopsy, but physicians are relatively comfortable and see them as stable. And it's now really the call to action to make sure that those patients are being treated and are being treated to the target level that KDIGO is now recommending.
Yeah, I think that's absolutely right, Peter. Thank you. Laura, the way that I would have you think about it is, in the short term, our opportunity is about upgrading patients that are on ACE or ARB, that have proteinuria above 0.5. That's aligned with the new expanded label, and it's aligned with now KDIGO's recommendations. As we think about long term, as Peter talked about in his prepared remarks, we will expect to see earlier diagnosis based on KDIGO, based on greater awareness, and as a result, we also expect them to be treated with combination therapy immediately. In fact, one of the most powerful things that struck me in the draft KDIGO guidelines is to say all patients need to be treated simultaneously with combination therapy. That includes a foundational therapy like Filspari.
So I think we're gonna see these sort of two stages of growth in the IgAN space. One is making sure you upgrade for those patients that are already under the care of a nephrologist, but we certainly expect there to be more, more growth over the long term.
Thanks very much.
The next question will come from Maury Raycroft with Jefferies.
Hi, I'll add my congrats on the full approval, and thanks for taking my question. Based on the expanded label, can you talk about how this impacts prescriber perception and maybe comment on go-forward pricing strategy based on the updated value proposition?
Sure. Thank you, Maury. I'll take the pricing one first, and I'll have Peter talk about the expanded label and impact on prescribers. What I would say is that today's focus really is about the full approval and certainly about KDIGO and the impact that we see in the growth moving forward, and as a matter of practice, we continue to look at the pricing and the value of our medicine, so certainly something we'll continue to look at, but today's focus very much is on the label. I think with that, Peter, why don't we have you talk about the potential impact on perception?
Absolutely. And thanks, Maury, for that question. I would start with building upon the conversation we just had with Laura. I think there's an opportunity to serve more patients, and we do this by targeting physicians that either have not yet prescribed or that have the experience and the potential to treat more patients. And as I mentioned in the prepared remarks, we have already identified a segment of about one thousand nephrologists that have been on the fence. They're having a positive attitude and belief to the Filspari profile, but just needed a bit more security on the longer-term efficacy and safety profile. And I think the full approval that we present today will allow that validation of Filspari's superior profile, including longer-term kidney preservation and safety, consistent to an active and maximally dosed comparator.
... Additionally, I would say that many physicians have initial experience, as I just mentioned to Laura. They have the experience with Filspari, but mainly in the higher proteinuria ranges, and when I mean higher, it's often in the 1.5- 2 proteinuria range. There's an opportunity to now go for the patients who have the lower proteinuria levels as well. In the draft guidelines that we discussed earlier, and Filspari's new label really allows for the identification of addressable patients at risk for progression with those lower proteinuria levels.
Got it. Really helpful, and maybe a quick follow-up question. Just based on the expansion, do you expect your orphan disease designation exclusivity could be extended?
Yes, that is a process that happens in parallel. That is our expectation, and we're working on that.
Got it. Okay. Thank you for taking my questions.
Thank you.
The next question will come from Yigal Nochomovitz with Citi.
Hi, thanks, and congrats as well on the approval. I just had one question on the data on the PROTECT trial. You show the complete remission for patients with less than 0.3 g proteinuria per day, three times higher complete remission with Filspari versus irbesartan. I'm wondering if you have similar data for the higher cutoff of the 0.5 g per day and what that would look like relative to irbesartan.
Thank you very much. Jula, why don't I turn that one to you?
Yeah, thanks for the question. We do, and that is in the Lancet supplement. So we had about 30% of patients achieve complete remission, which is defined at 0.3 versus about with Filspari versus about 10% with irbesartan. I do not recall the numbers off the top of my head for the threshold of 0.5, so I'm gonna encourage you, and we can send you the supplement thereafter, but we did look at other thresholds, 0.5 g per day as well as 1 g per day. All were directionally favorable and fairly comparable to the complete remission data. But as you can imagine, you get more patients to those higher levels of proteinuria because the complete remission is the hardest to achieve.
So, each threshold that's suggested in the KDIGO guidelines, we have significantly more patients achieving each of those important thresholds with Filspari versus Irbesartan. That's the important take-home.
Got it. Thank you.
The next question will come from Vamil Divan with Guggenheim Securities.
Hey, great. Thanks for taking my question. Congrats as well on the approval. I had one specific question. I don't know if this is too detailed, but I noticed in the highlights of the prescribing information on the first page of the PI, in the warnings and precautions sections, they have now removed hepatotoxicity and the embryo-fetal toxicity sort of call-outs, pointing people to sections five one and five two. Obviously, in those sections, the language is still there. I'm just wondering if there's any reason as to why that was removed, those two were removed from the front page. I don't know, it may be more of a question for the FDA, but just curious why they would choose to remove that from the new PIs. Any insights would be helpful.
Vamil, thank you for that. I wouldn't read into any changes. I think, Bill, you can speak to how FDA, you know, looks to labeling, but I wouldn't look at it in terms of any change to the safety profile or the REMS. Bill?
Yeah, you're correct, Peter. It doesn't reflect any change in attitude from the agency, but they do have a consistent push on every label to try and make it as short as possible. They're long documents, and they've got a concerted effort to be as brief as possible. So if they see something that's available in the label twice through multiple rounds of revision, sometimes those get cut down, and I think that's exactly why they were motivated to take it out of that early part of the label and point to the spot where it's discussed in detail.
Okay, thank you.
Moving on to Alex Thompson with Stifel.
Hey, great. Thanks for taking my question and congrats on the approval. I guess shifting gears to FSGS, I wonder if you could talk through really what the path forward would be following the PARASOL update. Sort of what would you be able to do next, and sort of what would be the path to talking to FDA about next steps? Thanks.
Thanks, Alex. Jula, why don't you take that one?
Yeah, so we're really excited about the work that the PARASOL group is doing because we really have always believed that there's a role for Filspari for the treatment of FSGS, and that's based on what you see in our data. The proteinuria reduction, favorable trends on eGFR, and really a high unmet need for these patients. And as PARASOL continues to work, they've already been meeting, continue to meet with a readout planned for next month. What our plan is to then engage with the FDA on a potential path forward, and after that, we'll give an update. But some more to come after they read out and as we have additional engagements thereafter.
And our next question will come from Cameron Bozdog with Bank of America.
Hey, this is Cameron Bozdog on for Jason. Congrats on the update and thanks so much for taking our question. I'm curious if you could provide any color regarding the timing of potential amendments to the KDIGO guidelines and how quickly you would expect an inflection in Filspari sales post a potential inclusion. And then what sort of impact is this likely to have, you know, especially for prescribers who may be a little bit more reluctant to enroll patients in the REMS? Thanks so much.
... Yeah. So, Cameron, thanks for the questions. I'll take the first one. The KDIGO guidelines have a very rapid turnaround. There's an open comment period now. They expect to have these completed in the fall, so it's a very quick turnaround. We largely believe that, you know, the way that Filspari is treated is gonna be consistent, which we are absolutely thrilled about. Peter, why don't you talk about how we can expect to see, you know, the impact of KDIGO on prescribing and future growth?
Yeah, I think the timing is perfect to have last Friday an update of the guidelines in KDIGO, and then today we have the new label. I think to have two of those major milestones within a week is definitely driving some tailwind in the opportunity for Filspari. So I absolutely believe there will be an acceleration. How fast it will go? Well, we are ready, our teams are ready and trained to really fully seize this opportunity. Yeah, we will see that acceleration soon.
And our next question will come from Ed Arce with H.C. Wainwright & Co
Great. Let me add my congratulations to your full approval. A couple questions from me. First, I wanted to ask, again, I know this has been touched upon, but in broadening your prescriber base, those roughly one thousand nephrologists that you were waiting for approval, wondering if you could further characterize how those physicians have been viewing Filspari, if any of them, for example, have yet tried Filspari in patients, or it's just a situation where you've communicated with them and they've expressed that they're really waiting for the full approval.
And then secondly, just wondering, given that the agency clearly focused on the total slope of the two-year data, if you can discuss discussions around that particular aspect, and in particular, how that might impact, you know, precedents going forward. Thank you so much.
All right, Peter, why don't you take the first one on nephrology prescribing and, let's see, Jula, you can take the one on the slope data.
Yeah. Thanks for the question. In the past, we have talked about, like, our targeting of the nephrology community, and I think there is about 10, 11 thousand practicing nephrologists in the US. We have been targeting six thousand nephrologists that we believe has about 85% of the addressable patient population for Filspari. We do measure within that target where the physician is based in the adoption continuum. And based on that, we have a good sense on physicians, where they are. And the 1,000 physicians that I was talking about are physicians that have a positive attitude towards Filspari. They believe in the product, but we're a little bit reluctant in waiting for, like, the validation of full approval.
Both from an efficacy perspective, what do they do on the long-term function of the kidney, as well as what is the longer-term safety profile? And I think we have now a very strong story to go back to those physicians. As I mentioned, many of those are already REMS-certified. They already have in mind a patient that they would want to treat with Filspari. So this is really our opportunity to go back and provide them with further confirmation of the profile of Filspari.
Ed, let me answer around the kidney function data. I'd say that the FDA was looking at how well Filspari can help patients preserve more kidney function over time. It wasn't about one exact measure, and you can see we have more than just total slope in our data because the figure is the change in kidney function year over year. You can see that in year two, you're saving more kidney function than in year one. That is what is the meaningful impact, is that with long-term treatment, patients can preserve more kidney function over time. That's what we understand they were looking for, and that's what's presented in our label.
I can't speak for future or precedent or what they're going to look at with, other therapies that work differently, but the most important part is the preservation of kidney function that was demonstrated with Filspari.
Great. Thank you.
We'll take a question from Allison Bratzel with Piper Sandler.
Hey, good afternoon, and congrats on the full approval. My question is a bit of a follow-up on some of the prior discussion on the REMS. I guess, do you have any color on the status of the enrollment in that two-year liver safety study that's part of the post-marketing requirements? Or, when would you expect that to be fully enrolled? And is it your sense that, you know, data from that study is needed or is gating to the SNDA submission for that modified REMS? You know, just curious, you know, how should we be thinking about that? Thank you.
Allison, thank you for the question. Let me answer the second one first. No, it is not gating. That is a requirement for the removal of the REMS, which we would see as a future prospect. And so part of the process that we're in now is evaluating, you know, specifically what FDA needs for modification. For example, getting to a less frequent, more aligned with how most patients are seen by their nephrologist. And, Jula, why don't you comment on the status of the safety study?
Yeah, certainly. So we have started that safety study and are enrolling into it, but I would say it's complementary to the additional data that we have, as Eric mentioned. We have patients who are increasingly being exposed month over month in the commercial setting. We have patients from PROTECT and DUPLEX as well with regards to exposure, and that's the data that we are planning to go back to have a discussion around the modification of the REMS. And as Eric said, we don't believe that that enrollment of that full PMR is required for that initial step of the discussion of the modification.
Got it. Super helpful. Thank you.
While we're waiting on the next question, we can just follow up on the answer to the rates in PROTECT of patients that got their proteinuria below 0.5. That's 51% with sparsentan or Filspari versus 24% on max dosed irbesartan. So still a profound improvement for those patients. As Jula mentioned, the most rigorous and unfortunately not often reported on other trials, is complete remission of getting below 0.3.
Ladies and gentlemen, this concludes the question and answer session of today's conference call. I'll hand the call back over to Nivi.
Great. Thank you for joining us for our FDA full approval of Filspari call. We are very excited about our path forward, and we'll continue to share more updates along the way. Have a great rest of your day.
Thank you. That does conclude today's conference. We do thank you for your participation. Have an excellent day.