This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk04: You are currently on hold for the Travere Therapeutics third quarter 2022 financial results and corporate update call. At this time, we are assembling today's audience and plan to be underway shortly. We appreciate your patience and please remain on the line. Good day and welcome to the Travere Therapeutics Third Quarter 2022 Financial Results and Corporate Update Conference Call. Today's conference call is being recorded. At this time, I would like to turn the conference call over to the Vice President of Investor Relations, Naomi Eichenbaum. Please go ahead, Naomi. Thank you, Kari.
spk05: Good afternoon, and welcome to Trivia Therapeutics' third quarter 2022 financial results and corporate update call. Thank you all for joining us. Today's call will be led by our Chief Executive Officer, Dr. Eric Dubé. Eric will be joined in the prepared remarks by Dr. Jula Enrich, our Chief Medical Officer, Tia Herma, our Chief Commercial Officer, and Chris Klein, our Chief Financial Officer. Dr. Bill Roach, Senior Vice President of Research and Development, will join us for the Q&A session. Before we begin, I would 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 10Q and 10K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, October 27th, 2022. And Trevier specifically disclaims any observation to update such statements to reflect future information, events, or circumstances. With that, let me now turn the call over to Eric. Eric?
spk12: Thank you, Naomi, and welcome to Tavir. And good afternoon, everyone. During the third quarter, we continued to execute toward our vision of being a leader in the global rare disease community. We did this through the continued development of our pipeline with the objective of positioning it for sustainable, diversified growth for years to come, and by strengthening our organization to support broad access to our approved medicines while being in a position to meet the need of patients as our potential new therapies become available. Notably, during the quarter, we continued our efforts to position sparsentin to become the first non-immunosuppressive therapy for IJ nephropathy and FSGS as a potential new treatment standard if approved. A couple of weeks ago, we provided a regulatory update on our NDA for sparsentin in IJ nephropathy that is currently under priority review with the FDA for subpart H accelerated approval. In that update, we were pleased to report that we had received a draft label on time. that no advisory committee is expected, and no new data or trials have been requested as part of the review process. During our late cycle meeting interactions, the FDA did unexpectedly ask us to incorporate liver monitoring into our planned REMS. I am pleased to report that we have submitted our proposed updated REMS, and we recently received confirmation of the expected three-month extension of our PDUFA target action date which is now February 17, 2023. Perhaps most notably, we have been very pleased with the continued enthusiasm for the strength of our clinical data supporting the profile of sparsensis. We have continued to hear this from the nephrology community since the update was provided a couple of weeks ago. I would also like to highlight that while the submission of a revised REMS has resulted in an extension of our PDUFA target action date, Our teams were well prepared and in a strong position to launch this November. This is a great testament to Peter and his teams, and to the whole organization, as it is no small feat to prepare for the launch of a potential new treatment standard. We will utilize the added time to further enhance our understanding for how we can best support patients and providers in the IJ and nephropathy community, and be even more prepared for a successful launch. Outside of the U.S., we were very pleased to have the EMA accept for review the conditional marketing authorization application for sparsentin for the treatment of IgA nephropathy. We look forward to working closely with our partner CSLV4 throughout the review process, and we expect a review decision on a potential approval in the second half of 2023. Lastly, on sparsentin, we continue to be pleased with the progress of our ongoing pivotal duplex study in FSGS. and we look forward to top-line data from the two-year endpoints in the first half of next year. If the data are supportive of an FSGS regulatory submission and assuming approvals in IgA nephropathy, we would anticipate being in a position to submit an SNDA in the second half of next year and a subsequent variation to our European CMA application. Elsewhere in the pipeline, our PEG to Batinase program for classical homocystinuria, or HCU, continues to advance. Jula will be going into a bit more detail shortly, but we're pleased with our regulatory interaction during the quarter, which enabled us to advance on the path towards utilizing a total homocysteine biomarker as a primary endpoint in a Phase III study. Let me now turn the call over to Jula for the clinical update. Jula?
spk00: Thank you, Eric, and good afternoon, everyone. We continue to hear regularly that physicians and patients are seeking non-immunosuppressive treatment options to treat their rare kidney disorders. Importantly, sparsentin is the only molecule in development which blocks two causal pathways in the pathophysiology of kidney disease progression, namely the endothelin and angiotensin pathways. The relevance of this dual inhibition in a single molecule is that sparsentin has shown the greatest reduction in proteinuria to date for a non-immunosuppressive agent in a pivotal study against inactive control in IgA nephropathy. If approved, sparsentin would be the first and only non-immunosuppressive treatment approved for IgA nephropathy, and we continue to have confidence that it can ultimately become a new treatment standard. As it relates to our NDA under priority review for sparsentin in IgA nephropathy, we noted in our update two weeks ago that we were pleased to have received a draft label and that the overall process appears to be moving well. As Eric highlighted, we did receive an unexpected request for our REMS to include liver monitoring. I will reiterate that FDA communicated to us that this request is being made in part because serious drug-induced liver injury has been associated with other treatment options that intervene in the endothelin pathway and that the sparsentin database will not be final while being reviewed under the accelerated approval pathway. Additionally, it was highlighted to us that there was a desire to have education and monitoring, as this would be the first time nephrologists would be using a medicine which blocks endothelin. Most importantly, there have been no reported clinical diagnoses of sparsentin-related liver injury in the program to date, and are adverse events of interest related to ALT-AST elevations in both of our phase three studies, spanning nearly 800 participants at the time of the data analyses, were comparable between sparsentin and active control erbisartan. As you heard from Eric, we have submitted our updated REMS proposal back to the FDA. Our goal is to make the REMS effective for liver monitoring and convenient for patients, their physicians, and support staff. And there have been a number of examples that we've been able to learn from in the recent weeks. It's also important to note that many nephrologists and their practices are already familiar with the REMS process. Additionally, nephrologists routinely order and monitor labs for every patient, so monitoring liver function tests should be seamless with their current clinical practice. We recently received confirmation of the three-month extension and our new PDUFA target action date of February 17th of next year. We look forward to continuing to work with the FDA through the labeling and review process. We will use the opportunity provided by the extension to further our IJ nephropathy disease state education for physicians and our work with the supportive patient advocacy groups in the nephrology field. Our FSGS program for sparsentin continues to progress as planned. We believe that we are on a path to an S&DA submission next year if sparsentin is approved for IJ nephropathy And the two-year data in our pivotal Phase III duplex study progresses in a favorable manner. To that end, we are pleased with the continued conduct of both the ongoing duplex and PROTECT studies, and we remain on track for the top-line readouts from the two-year endpoints next year. For FSGS, we expect this will be in the first half of 2023, and for IG nephropathy, in the second half of 2023. Lastly, on sparsentin, ASN Kidney Week is occurring next week. This is an excellent opportunity for us to engage with the nephrology community. We look forward to sharing insights from our growing body of research for sparsentin in both IJ nephropathy and FSGS, including our two oral presentations and nine poster presentations. I'll now turn to our PEG2Batinase program, which continues to advance towards phase three development. I am pleased to report that we believe we have line of sight to completing enrollment in the sixth cohort of our ongoing Phase I-II Compose Study and that we continue to gather data from patients from the first five cohorts in the Open Label Extension, all of which will be critical in forming our views for a pivotal study. We also completed our second official biomarker interaction with the FDA and believe we are making sound progress towards utilizing total homocysteine as a primary endpoint in a pivotal study. We'll be utilizing our learnings from this interaction to guide our upcoming multidisciplinary meeting afforded by breakthrough therapy designation to further align on the design of a pivotal study. In parallel to the clinical and regulatory work, we continue to work through the burden global supply system to make progress on building supply for the pivotal phase of development and commercial readiness. Overall, I am very pleased with the continued progress of our pipeline and the potential for us to continue to deliver new, greatly needed treatment options to the rare disease community. I'll now turn the call over to Peter for the commercial update. Peter?
spk16: Thank you, Joanne. During the third quarter, our commercial organization continued to deliver our approved products and build further momentum towards the potential launch of Spar Centrum and IGA nephropathy As for the approved products, we have another quarter of solid demand across our commercial portfolio. For Fiola, we are pleased with the continued performance despite the evolving competitive landscape. As we have talked about throughout the year, we are seeing the impact of generic dynamics affect net sales, and we expect this to materialize further in the quarters ahead. Overall, we remain pleased with how we have continuously identified treated and supported patients in the cystinuria community. Our bile acid portfolio continues to deliver solid growth in the third quarter. The Colbond field team has had a longstanding dedication to educating pediatric geneticists as well as hepatologists, and these efforts have been key to Colbond's continued success. Our established commercial footprint allows us to build upon our strengths as we prepare for successful launch of sparsenton in IgA nephropathy, if approved. Over the last eight years, our commercial organization has built a track record of strong execution in identifying, treating, and serving people affected by rare diseases. This has allowed patients timely access to treatment and support for approved indications. We completed our recruitment efforts to expand our team in preparation for the sports income launch in IGA nephropathy and have built a seasoned nephrology field force. This established sales group has an average of nearly 20 years of specialty experience, mostly within nephrology. The team has completed initial trainings and is gaining familiarity with the communities they expect to serve. Of note, our team was prepared for a launch of SparSymptom in November, if it would have been approved. And as a result, we have great confidence that we will be even better positioned in February. After speaking to patients and nephrologists about Nurem's requirement for liver monitoring, we believe that the potential for SparSymptom to become a new treatment standard in IgA nephropathy remains unchanged. As you heard from Jula, The need for non-immunosuppressive treatment options that address the active pathway for people living with progressive IgA nephropathy has never been greater. As a dual endothelin and angiotensin receptor antagonist, Sparxentrum is the only treatment in development that inhibits two critical pathways in the pathophysiology of the disease. We believe that is what has contributed to sparsenton demonstrating an ability to reduce proteinuria by nearly 50% in a pivotal phase three study against an active control. With our results and the fact that sparsenton would be the first non-immunosuppressive treatment indicated for IgA nephropathy if approved, we continue to believe there will be an addressable patient population of 30 to 50,000 patients at launch in the United States. Based on what we know today, the initial onboarding and education in the REMS process and the frequency of monitoring could result in a more gradual uptake than we had originally expected. But we will continue doing additional research to further understand these dynamics. We have already learned quite a bit from studying some of the other programs that have done very well with similar types of REMS. We believe the key to our success will come in proactive education and providing the support needed to make the process most convenient for physicians, their staff, and patients. With the added time from the PDUVA extension, our team will be even better positioned for a successful launch of sparse income for IGA Neuropathy, if approved. Let me now turn the call over to Chris for the financial update. Chris?
spk09: Thank you, Peter, and good afternoon, everyone. I'm pleased with the continued financial strength of our organization. We're well positioned to support our ongoing development programs, as well as the upcoming potential launches that can meaningfully change our growth trajectory. For the first quarter of 2022, we reported total revenue of $53.5 million, consisting of approximately $50.8 million in net product sales and $2.7 million in collaboration revenue from our European collaboration with CSL v4. This compares to $54.2 million in net product sales and $14.0 million in collaboration revenue reported for the same period in 2021. We reported a gap net loss of $69.7 million for the third quarter of 2022. After adjusting for non-cash expenses and income tax, we reported a non-GAAP net loss of $48.9 million for the third quarter of 2022. On a GAAP basis, research and development expenses were $59.3 million for the third quarter of 2022. The increase compared to 2021 is largely attributable to the continued advancement of the sparsent and pegged to bad news programs, including increased headcount as well as medical affairs activities. On an adjusted basis, R&D expenses were $54 million for the third quarter of 2022. Relevant non-cash expenses for the third quarter included $5.3 million of stock-based compensation and amortization. On a gap basis, selling general and administrative expenses for the third quarter of 2022 were $57.5 million. The increase compared to 2021 is largely attributable to launch preparations, including increased headcount and commercial support. On an adjusted basis, SG&A expenses for the third quarter of 2022 were $45.4 million. Significant non-cash adjustments for the quarter consisted of $12.1 million in stock-based compensation and depreciation and amortization. For the balance of 2022, we anticipate a modest increase to operating expenses from our third quarter levels, and we continue to have a strong financial foundation. We ended the third quarter with $506.3 million in cash and cash equivalents. Importantly, we believe this cash balance can support our operations into 2024. This takes into account the extension of our PDUFA date into the first quarter of next year, the potential for further competitive dynamics for Thiola, investing in sparsentin launches for both IGA nephropathy and FSGS, advancing PEG-tibatinase, as well as the milestone payments we expect to pay related to regulatory achievements for sparsentin and PEG-tibatinase. I'll now turn it back over to Eric for his closing comments.
spk12: Eric? Thank you, Chris. With confirmation of our new PDUPA date and the ongoing CMA review process in Europe, we believe we are well positioned for sparsensin to become the first non-immunosuppressive treatment approved for IJ nephropathy in the U.S. and Europe. With the added time afforded to us by the extension in the U.S., our experienced commercial and medical affairs teams will be working even more diligently to enable sparsensin to become a new treatment standard if approved. In parallel, we will look to add to our sustainable growth with the upcoming readout from the duplex study of sparsentin and FSGS in the first half of next year and the continued advancement of the PEG-2-Batinase program towards a pivotal study in 2023. Let me now turn the call over to Naomi for Q&A. Naomi?
spk07: Thank you.
spk08: Naomi, if you're there, you might be able to.
spk04: If you would like to ask a question, please signal by pressing star one on your telephone keypad. If you are using a speakerphone, make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star one to ask a question. We will take the first question from the line of Maury Raycroft with Jefferies. Mr. Raycroft, your line is open.
spk01: Hi, thanks for taking my question and congrats on the update. Starting off, wondering if you can talk more about what your proposed REMS plan is and talk more about the recent examples that you've learned from, which Julo mentioned. And lastly, do you have evidence that would support less frequent REMS testing, such as every three months, if you can talk about that?
spk12: Sure, Maury. Great question. Thank you for that. Well, I'll certainly turn it over to Jule to provide a bit of detail on the proposed REMS and what we've learned from other REMS, particularly those within the renal space. What I would remind you and everyone is that the REMS that is submitted is still proposed. We do not yet have a final REMS designed and agreed with FDA, nor do we have a final label. But with that in mind, Jule, I'll turn it over to you to provide a bit more detail on those questions.
spk00: Yeah, thanks, Maury. So we submitted back monitoring that's consistent with how we monitored within our phase three studies. And as a reminder, we monitored quarterly within our trials, and this was effective. We didn't identify any cases of concern of liver injury. We do know there's a number of other analogs, less that are within the rare nephrology space with regards to liver monitoring. We know Tolvaptan And there's a cadence of different levels of monitoring that has been done from slightly more frequent monitoring, which then tends to decrease over time. I will also point out that there's a number of agents that nephrologists are familiar with that we're quite aware of, like MMS that's used within the patient population, that are familiar with REMS processes and ESAs, and then some other in the transplant pace. space and importantly that hasn't impacted the utilization of these agents and really they're important for education of the nephrologist their practice and the patients and ultimately our goal is to make it convenient and effective.
spk04: If you find that your question has been answered you may remove yourself from the queue by pressing the star key followed by the digit 2. And we'll take our next question from Greg Harrison from Bank of America.
spk10: Hi, guys.
spk04: Your line is open.
spk10: Hey, guys. Thanks for taking our questions. First one is, do you have a sense on whether the cephalomide chemistry has anything to do with FDA's view of the liver risk for sparsitin?
spk12: So, Greg, thanks for that question. And no, we are not aware of any link that the FDA is looking to make there. We are aware of some misinformation about sparsentin in this regard that was circulating following our regulatory update two weeks ago. Now, the FDA has not in any time during our review of NDA or in our interactions mentioned anything related to the chemical structure or a sulfonamide group being related to the need for liver monitoring or the risk of liver damage. What they did raise, however, really is two important aspects in them making this decision. The first is the need for additional monitoring based on the potential class risk within agents that block endothelin. and the other is an evolving data set for sparsentin under accelerated approval. And that was really the rationale, not based on what has been sort of a hypothesis that arose about 20 years ago with the first approval of an ERA and whether the liver damage risk was associated with the sulfonamide group. What we do know now is that it's much more multifactorial, but this hypothesis has not really been proven out Most importantly, there have been no reported clinical diagnoses of sparsentin-related liver injury in the program to date.
spk10: Okay, that's helpful. Thanks for that. And then one follow-up is, do you expect that there will be any similar liver monitoring requirements in XUS geographies? And if so, could there be any change to your timing assumptions?
spk12: Sure, so we certainly have looked at what other agents in Europe have for their label as well as potential monitoring, and I'll ask Bill to cover what we've learned thus far.
spk14: Certainly, Eric. Our marketing application in the EMA was recently accepted for review, so we haven't engaged with active discussions with EU reviewers at this point, so we don't know their perspective. on potential monitoring for liver enzyme elevations. If you look at the process in Europe, they don't really have an analog to REMS. They take a slightly different tack where they focus predominantly on education. So we'll be able to assess this in the future as we get more interactions with the EMA.
spk10: Got it.
spk07: Thanks for taking the question. Thanks, Greg.
spk04: We'll take our next question from the line of Joseph Schwartz from SVB Securities. Please go ahead.
spk02: Great. Hi, all. This is Will on for Joe. Thank you for taking our questions today, and congrats on the continued progress this quarter. So I guess one for us to start, you know, with the addition of the liver REMs and the expected Black box warning, some may view the perceived risk-benefit profile of sparsentin as changed a bit. So have your assumptions of the addressable market also changed, and do you still expect that similar kind of demographic to be addressable at the launch? Thank you.
spk12: Yes, it's a great question, Will. And I'd say that based on our assumptions, that has not changed. And, you know, I need to caveat this by we've not seen the final label, but based on what we understand and how others have labeled for liver monitoring, we do not believe that our calculations of addressable population that Peter mentioned in his prepared remarks will change. But I'll ask Peter to comment a little bit more about how he and his team are thinking about the potential opportunity upon approval.
spk16: Certainly, Eric, and thanks, Will, for the question. I think it's important to realize that this is a rapid-progressing patient population with limited treatment options. So the unmet need remains high, especially for a product with a non-immunosuppressive profile that has demonstrated to reduce proteinuria with nearly 50%. As you may have seen over the last few years, research has consistently called out that nephrologists characterize paracetamol as the most desirable product in development. So within that context, if you look at the liver monitoring within the REMS, I think there's good analogs out there, and Julo was talking about it, that have made it convenient for patients and physicians. And these products were successful in their commercial uptake. So we believe that the profile of sparsantin remains unchanged and has the potential to become foundational treatment for IgA and nephropathy patients. REMS may take some additional educational and logistical efforts, and that may have some impact on the initial uptake. But we are further informing ourselves what it could look like. But most importantly, we have the experience with our hub and patient services infrastructure to provide customized patient solutions that will support the REMS implementation. And it's also good to realize that many progressing patients see their nephrologist on a quarterly base and quite often even monthly. And to Julio's earlier point in the script, obtaining lab values is a standard practice to inform these patient visits.
spk02: Great, thank you. And then if I could just sneak in a quick follow-up here, you know, looking next year to the early days of the launch, you know, are there any analogs for kind of the gradual uptake you might expect with the liver monitoring, and how are you thinking about the overall cadence for the first year? Thank you.
spk12: Yeah, Peter, why don't you take that one?
spk16: Yeah, I think Julia was mentioning Tolvaptom. I think that's a good analog in rare nephrology. That was launched in 2018, has been successful in their uptake, but I think that's a good benchmark for us.
spk12: Yeah, and I think what's important is the work that Peter's team is doing to, you know, further refine our assumptions and estimates through market research with a revised target product profile that reflects liver monitoring. So we will be able to provide a bit more detail on that in the future, but I think as you point out, we've been focused on the analogs and You know, it does suggest that long-term we will be successful or can be successful at the launch. But as Peter mentioned, you know, it's going to take a bit of education up front, and we want to be cautious just in assuming that that could lead to, you know, slightly more gradual uptake to begin with.
spk04: We'll take our next question from the line of Carter Gold with Barclays. Please go ahead, sir.
spk13: Hi, this is Justin on for Carter. Thanks for taking the question, and congrats on all the progress. I'm wondering if you can provide sort of a rough estimate around the number of patient years' worth of data you have for patients that have been treated with sparsen, and related to that, if there's sort of a hurdle with thinking about how substantial the database might need to be to revisit the REMS requirement down the road?
spk12: Yeah, Justin, thank you for the question. And, Jula, I will turn that over to you.
spk00: We haven't publicly released the amount of patient years that we have. What I can say is that we are going to present at ASN upcoming some long-term data that we have from Duet. Realize that this is under accelerated approval, so as we've released before, how much data that we have of patients. Under accelerated approval, we don't have the full data set or analysis. So as we said, we have 800 patients on our clinical trials. Half of those are on sparsentin. As we've said before, we have about 1,200 patients who've been exposed to sparsentin, but some of those were earlier trials where patients got shorter duration of exposures and treatment time periods. So some of them might not have been exposed for a longer duration. And to your second point of what is it going to take, that's going to be a continued conversation of how much data we will need to present over time. Of course, when we complete these trials next year, we'll have additional exposure from our open label extension studies, both in duplex and protect as they complete and read out next year. And additionally, assuming we get approval, we'll have patients who have gotten commercial therapy to be able to submit that data. So it'll be a continued conversation over time. Okay, awesome, thank you.
spk07: Thanks, Justin.
spk04: We'll take our next question from Tim Lugo from William Blair. Please go ahead, sir.
spk03: Thanks for taking my question. Congratulations on the progress. You know, we've seen REMS become something that is maybe proprietary for companies that have implemented them for certain therapies. I guess one of your thoughts on maybe a REMS could dampen uptake but also impact the sale value of the sparsense enfranchise. And then maybe can you discuss the possibility that REMS, that the REMS program maybe is a bit different for certain patient subgroups, you know, like I'm thinking maybe pregnant patients or patients on certain concomitant therapies.
spk07: Yeah, Tim, thanks for the question.
spk12: And I'd say first, you know, we'll be able to assess the full impact once we have alignment with FDA on the final design of the REMS. But based on our work and assumptions to date, we believe that it shouldn't have a major impact on the uptake or the, you know, the impact on practices. You know, and I think as Jula alluded to, what we see is that whether it's monthly or quarterly, this very much aligns with how many of these patients are being treated, you know, for their condition anyway. And I'll turn it over to Jula on the rest of the question.
spk00: Yeah. Just to clarify, Tim, was your question around how they're going to monitor for embryo fetal toxicity? Can I get a clarification on that and subgroups?
spk03: Yeah, I guess so, sure. I mean, I'm just thinking any sort of different monitoring in certain subgroups versus others and maybe how that could alleviate FDA concerns if you include monitoring on pregnant patients versus broader monitoring.
spk00: Well, let me clarify that everyone's going to have to sign up for embryo fetal toxicity and this is a consistent thing that is done for all patients to confirm their reproductive potential. So across the ERA class, every single participant will have to sign up and document that because you cannot confirm what their reproductive potential is going to be. And there's education around that up front when they get a prescription. It's pretty simple and they attest to it. And then there's a monthly pregnancy testing that's done for people who can become pregnant. And this is across class.
spk07: Okay, all right, thank you.
spk04: We'll take our next question from the line of Lisa Baco from Evercore ISI. Please go ahead, ma'am. Hi there, thanks for taking the question.
spk06: Could you talk about your timing for final data, so final data with the EGFR endpoint? When do you think you might have that? When do you prepare? Do you think to file with SBA? Do you think this could start to address some of the concerns? And then, yeah, that's my first question.
spk12: Okay. Thanks, Lisa. It was a little bit difficult to hear, so let me just confirm. You're asking for confirmation of the timing of the final data from our trials as well as what our expectations are about those data, including EGFR, addressing any questions from the FDA. Is that right?
spk06: Yeah, sorry, I'm on a plane.
spk12: That's okay. That's all right. Well, thank you for joining the call. So, yeah, I think, you know, we are on track as we've guided throughout the year that the final data from Duplex will be available in the first half of next year, and then the final two-year data from Protect will be available in the second half of next year. And as we get closer to bringing the data sets in-house, we'll be able to further refine the the timing, perhaps in a tighter window. But we are on track for delivery of those data sets, and we'll certainly work diligently to package those for submission to the FDA, both for full approval for IG nephropathy, for full approval as an SMDA for FSGS, but also in assessing the safety data to assess the potential for any adjustment or removal of liver monitoring as part of the REM. So I think, you know, we'll be able to make further kind of assessment once we see those data and have further conversations with the agency. But at this point, I think that's certainly our intent and the plan for next year.
spk06: And can you remind us on the size and duration of that database, just in context?
spk12: Sure, and I'll turn that over to Jule in terms of the size and also what data will be part of that submission.
spk00: Yeah, certainly. So for duplex, recall that we have about 370 patients who got randomized to active treatment versus sparsentin. So we will have that. And realize that patients are eligible to roll over to active treatment with sparsentin once they complete the two-year trial. So we'll have patients who have rolled over, so additional data. For the PROTECT trial, we have about 404 patients who got randomized to sparsentin versus active control. And again, similar study design that the patients who got erbisartan will then roll over. So we'll have additional exposure in those open label extensions where patients roll over to active treatment. So in totality, roughly about 800 patients. And again, we had significant patients in the early days of hypertension where we have patients, but shorter duration of exposure in some of those early studies. And then additionally, we have the DUET study, which has about 108 patients who got exposed to different doses. And we have patients who have now been on treatment for really up to almost seven years now.
spk06: Right, and when you look at other packages that other companies have filed to get these liver testing removed, what size and what duration are you seeing out there of data that was submitted?
spk12: Yeah, it's difficult to say. I think particularly because within this instance, we know that FDA and the cardiorenal division is looking at this through the lens of a subpart H accelerated approval. We haven't heard anything with regard to a particular threshold or number of patients. It's really particularly based on an evolving data set within the diseases that we're studying. So I think if we do certainly find further kind of insights, we will share those as we've tried to do along the way. But I think the other aspect that I would just remind you, Lisa, is that this is rare disease, and the others were non-rare and were submitted for full approval. So I think it's a unique situation that we continue to navigate and certainly will provide FDA with a much more complete data set when they are finished next year.
spk06: Thank you so much.
spk12: Thank you.
spk04: We'll take our next question from the line of Laura Chico from Wedbush Securities. Please go ahead, ma'am. Good afternoon. Thanks for taking the question.
spk15: I wanted to follow up on one earlier comment, Jula, that I think I heard. I apologize if I didn't hear this correctly. I think you said sparsentin is showing ALT-AST elevations that were comparable to erbisartan in the studies. If I recall correctly, herbicartin rates of ALT-AST elevations, I think, are low single digits. I'm not sure if that's correct, but I'm wondering, is it comparable in terms of the rates of incidence or in terms of the magnitude of increase, or is it both with respect to sparsetin? And then I have one quick follow-up.
spk00: So we collected it with regards to rates. of increases because that was our pre-specified adverse event of interest. And that adverse event of interest was three times the AST ALT elevations, which we monitored prospectively and also submitted to our DSMB for monitoring. And that's what we've released that was similar between the two arms and comparable.
spk15: Got it. Okay. And then I apologize if you have not disclosed this, but can you confirm were the elevations you've observed so far with sparsensin in the IGAM setting or is this in FSGS dose patients? Thanks very much. Across the trials.
spk07: So we've looked at it in totality. Got it. Thanks.
spk04: We'll take our last question from Ed Arce from HC Wainwright. Please go ahead, sir.
spk11: Great. Thanks for taking my questions, and congrats on the progress in the quarter. A couple questions from me. Firstly, I just wanted to confirm sort of some perspective shared here today on the call with regard to the liver monitoring and the REMS. As you said, you've taken a second fresh look now over the last couple weeks at some analogs and the history there, and I think you had said that really you don't expect, as others hadn't, any impact to utilization ultimately. Question is, a couple weeks ago when you had mentioned, and I think you mentioned earlier today, a more gradual uptake is your impression. So I just wanted to clarify that although the longer term remains sort of unchanged, you're really more focused on the initial uptake part that could have a little more gradual uptake. And then I will follow up.
spk12: Thank you, Ed, for the question. And that is a correct assessment that we've made. We believe that the need for... Liver monitoring in REMS does not change the addressable population, nor does it change the clinical profile of sparsentin or the unmet need. But we do recognize that this will require some additional education of nephrology practices, as well as just having clinicians and patients sign up initially. And so that we do believe is going to have that impact short term, but certainly long term we believe that that is not going to be an issue. And that's really what we've gleaned from others who have launched successfully with the REMS. And as we had mentioned previously, we will continue to refine those assumptions and provide any guidance once we've completed the market research to make sure that we have a contemporaneous view of our launch assumptions.
spk11: Okay, understood. Thanks for that. And then secondly, just turning to PEG-2-Batinase, what are the barriers that FDA is considering before accepting total hemocysteine as the pivotal study primary endpoint? And what gives you confidence that ultimately you would be successful in securing that? And in that regard, does the six-cohort data from COMPOSE play any role in that? Thank you.
spk12: Yeah, thank you for that question, particularly on tegdebatinase. And as we close out October, which is Homocystinuria Awareness Month, it's, you know, one that we recognize is certainly a community that has a high unmet need. And I think that's really driven our desire to have a biomarker endpoint which will facilitate, you know, the next phase of development. I'll ask Bill to talk a little bit about what that might entail and what we believe FDA may be looking for. Bill?
spk14: Certainly. We've gone through several interactions with the agency discussing the utilization of total homocysteine as an endpoint. We believe that we've gotten agreement there from a big picture view of using total homocysteine as the primary endpoint in a phase three pivotal trial, but what we haven't completed and is important detail are the specifics of that trial and how you utilize it. Is that endpoint as a threshold or a percent reduction? The overall design of the trial, that work we're still working on with the agency and having received breakthrough therapy designation, we have a multidisciplinary meeting coming up before the end of the year and then subsequent interactions are a little bit easier to have under breakthrough. So we look forward to having those discussions. You asked also about the sixth cohort. That is testing a higher dose as well as a lyophilized formulation. So we need to see the data in order to make a final dose selection and to confirm the safety and tolerability of the lyophilized formulation as opposed to the liquid formulation that was in the earlier. So it's on the path to phase three, but it's not dating to further discussions around trial design.
spk07: Great. That's helpful. Thanks so much. Thank you, Ed.
spk04: That concludes today's question and answer session. At this time, I will turn the conference back to Ms. Eichenbaum. for any additional or closing remarks.
spk05: Great. Thank you, everyone, for joining us this afternoon to learn about Travere's recent updates. We have exciting milestones ahead and look forward to sharing more updates along the way. Have a great rest of your day.
spk07: Bye-bye. That concludes today's conference. Thank you for your participation, and you may now disconnect.
Disclaimer