Good morning. My name is Lisa and I will be your conference operator today. At this time, I would
like to welcome everyone to the Traverse Therapeutics Top Line Interim Results from Phase III DUPLEX Study of the Sparsentan and FSGS Conference Call. All lines have been placed on mute to prevent any background noise. I would now like to turn the call over to Mr. Chris Klein. Please go ahead, sir.
Great. Thank you, Lisa. And good morning, and thank you all for joining us on short notice today to talk about the top line interim results from our ongoing Phase III DUPLEX study as farsentan in FSGS. A copy of the press release announcing the results are available on the Investors section of our website. Today's call will be led by Chief Executive Officer, Doctor.
Eric Dube. Eric will be joined for the prepared remarks by Doctor. Noah Rosenberg, our Chief Medical Officer and Doctor. Bill Roat, Senior Vice President of Research and Development, will join us for the Q and 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 of our Forms 10 Q and 10 ks filed with the SEC. In addition, any forward looking statements represent our view only as of the date such statements are made, 02/02/2021, and Travear Therapeutics 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, Chris, and good morning, everyone. Thank you for joining us today to talk about the promising top line interim results from the ongoing DUPLEX Study released earlier today. First and foremost, I would like to thank the patients and their caregivers, patient advocacy organizations, and investigators and site staff for their ongoing commitment to our study, particularly in light of the ongoing COVID-nineteen pandemic. Collectively, they have enabled DUPLEX to become the largest interventional study in FSGS to date. And their continued participation has been instrumental in getting us to this important milestone today.
There's been a lack of innovation in rare kidney disorders for decades. And new treatment options are desperately needed to slow the progression to end stage kidney disease, transplant, and dialysis. For the more than forty thousand patients with FSGS in each of The U. S. And in Europe, there are no approved medicines indicated for their condition.
Physicians treating people living with FSGS rely on therapeutic strategies that are limited to ACE inhibitors, ARBs, calcineurin inhibitors, and steroids. And they are often not enough, either due to limited efficacy or long term safety issues. People with FSGS live every day coping with the fear of seeing their proteinuria increase, signaling progression towards dialysis. It is estimated that thirty to sixty percent of people living with FSGS progressed to end stage kidney disease within five to ten years. And fifty percent of patients with severe FSGS progressed to kidney failure within one thousand days of diagnosis.
This is why we have made our sparsentan investigational programs the highest development priority at Trevere over the last several years. Today I am pleased to report that our phase three DUPLEX study of sparsentan achieved a statistically significant response on the clinically meaningful interim proteinuria endpoint compared to irbesartan after thirty six weeks of treatment. Based on the data from the interim analysis, we intend to pursue submissions for accelerated approval of sparsentan for FSGS. We will continue our engagements with regulators in the 2021, with the objective of sharing additional details from the ongoing study and establishing next steps for filing with the available data set. In tandem, we plan to continue our NDA and CMA preparations, as well as commercial and medical readiness activities to prepare to bring this important treatment to people living with FSGS if approved.
Before I turn the call over to Noah, I'd like
to remind everyone that DUPLEX is an ongoing study. And as we previously guided, we can provide only limited detail from this interim readout in order to maintain the trial integrity for the full study out to one hundred and eight weeks of treatment. Now I'll turn it over to Noah. Noah?
Thank you, Eric, and good morning to you all. I'd like to start by repeating Eric's gratitude for all those participating in our DUPLEX study. As you'll recall, the ultimate goal of our sparsentan programs is to deliver the first novel nonimmunosuppressive medicine indicated for people living with FSGS and IgA nephropathy. The ongoing DUPLEX Study in FSGS is a landmark trial, and one of the first of its kind. We believe that it has the potential to not only support eventual approval of sparsentan, but to also significantly advance the understanding of FSGS for the nephrology community.
It has been informed and designed with the key learnings from the prior successful DUET study of sparsentan in FSGS, and data from more than 600 subjects in aggregate from the program's clinical history. The DUPLEX Study is a global, randomized, multicenter, double blind, parallel arm, active controlled Phase III clinical trial assessing the efficacy and safety of sparsentan in three seventy one patients ages eight to 75 years with primary FSGS. After a two week washout period, patients are randomized one to one to receive either sparsentan or orbusartan, the active control, and a representative RAS blocker, which is considered standard of care in the absence of an approved medicine for FSGS. Patients are then dose titrated over a two week period to the maximum dose of eight hundred milligrams of sparsentan or three hundred milligrams of irbesartan as tolerated. Overall, we continue to be pleased with the conduct in the study and the commitment of the investigators and site staff.
Because the trial is ongoing, we must remain vigilant in the conduct of the trial to ensure a high quality completion. This means that we will focus on maintaining strong patient retention, and minimize any chance of biasing or inadvertent unblinding of the trial. As such, today we will not be able to provide data beyond the planned interim proteinuria assessment. The DUPLEX Study protocol provides for an unwind analysis of at least 190 patients to be performed after thirty six weeks of treatment to evaluate the interim efficacy endpoint, which is the proportion of patients achieving an FPRE or FSGS partial remission of proteinuria endpoint, defined as a UPC, or urine protein to creatinine ratio, of less than or equal to 1.5 gram per gram, and a 40% reduction in UPC from baseline at week thirty six. Complete or partial remission of proteinuria is widely regarded as beneficial in the slowing of progression of FSGS, and is recognized as a treatment goal amongst nephrologists.
Achieving FPRE has been shown to be a clinically meaningful and robust correlate of kidney survival in patients with primary FSGS. This has been demonstrated across five independent cohorts from clinical trials in the field. As Eric mentioned, the DUPLEX study met its interim FPRE endpoint. After thirty six weeks of treatment, forty two percent of patients receiving sparsentan achieved FPRE compared to twenty six percent of irbesartan treated patients. And the results were statistically significant with a p value of 0.0094.
To date, sparsentan has performed in line with our expectations for FPRE response, and consistent with the findings from the Phase II duet study. The confirmatory primary endpoint of the DUPLEX study to support full regulatory approval is the rate of change in eGFR over one hundred and eight weeks of treatment. As of the time of the interim analyses, available long term eGFR data for the confirmatory endpoint were limited given the long term nature of this endpoint. Consistent with the DUPLEX Study Protocol, patients will continue in a blinded manner to assess the treatment effect on eGFR slope over one hundred and eight weeks. From a safety perspective, we are very pleased with the interim results, which indicate sparsentan has been generally well tolerated and that the safety profiles in the study to date have been generally comparable between treatment groups.
Of note, the independent data monitoring committee recently completed their fifth scheduled meeting to assess safety in both DUPLEX and ALPROTECT study in IgA nephropathy. And I am pleased to report that the DMC recommended both studies proceed as planned based upon their safety review. We will not be able to provide further data on efficacy or safety because this is an ongoing trial. And we must do all we can to protect the blind and full completion of the trial to ultimately support full approval. I would like to commend our internal biostatistics and medical teams for achieving an expeditious and high quality readout.
These interim results build upon the foundational evidence generated by the Phase II DUET study. We believe these data provide further support for the potential of sparsentan, an innovative product candidate combining selective endothelin A receptor and angiotensin receptor blockade to treat the high unmet need in rare kidney disorders, if approved. I would like to again thank the patients, their caregivers, investigators, and site staff, whose continued commitment is critical to reaching this milestone and to ultimately completing this important study for those living with FSGS. As Eric mentioned earlier, we look forward to meeting with regulators in the coming months to share the available data set and establish next steps for potential accelerated approval. I'll now turn the call back over to Eric for his closing comments.
Eric?
Thanks, Noah. There is
a clear unmet need in FSGS, and we are very encouraged by the data released from the DUPLEX study today. We believe this interim analysis brings us another step closer to realizing our goal of delivering a new treatment standard for people living with FSGS. Moving ahead, we look forward to engaging with the FDA and EMA with the available data set from DUPLEX, as well as the robust and supportive data from our previous Phase two DUET study to establish next steps in our intent to pursue accelerated approval. Additionally, we will remain focused on maintaining excellent study conduct and integrity in DUPLEX to enable a high quality readout of the confirmatory eGFR endpoint. Finally, we are looking forward to the upcoming readout of the PROTECT study of sparsentan in IgA nephropathy.
PROTECT remained on track to deliver top line interim results from its thirty six week proteinuria endpoint in the third quarter of this year, and if successful, could serve as the basis for accelerated approval submissions of sparsentan in IgA nephropathy as well. Let me now turn the call back over to Chris for Q and A. Chris?
Great. Thanks, Eric. Lisa, can we go ahead and open up the line for Q and A please?
Your first question comes from the line of with Jefferies.
Hi everyone. Good morning and much congrats on the update today. Thanks for taking my questions. So on your 3Q20 call, you implied that it might be important to see a positive trend in eGFR at week thirty six. So I'm not necessarily asking for data on this because it seems like you're not providing much more data.
But just asking if there was a positive trend in eGFR at week thirty six that you can comment on.
Yeah, thank you, Maury, for the question. And you're right. As we mentioned, we're going to be very limited in the information that we share. And, you know, certainly we will be looking at data that are going to be critical for our submissions to regulators. And, you know, evaluation of the early read of eGFR will certainly be part of that, along with other measures of efficacy and safety.
Noah, is there
anything else that you'd like
to add to Maury's question?
Yeah, I think, you know, eGFR is a long term endpoint, you know, that really is measurable at 108. So any look right now would not be fully mature. And I think to your point, if we were to speak about it, would potentially introduce biases to the trial. So we need to keep those patients in the study long term. This is aligned with the regulatory view and in the best interest of the study conduct.
So I
think you covered it well, Eric.
Got
it. Thank you. And I'm also wondering if you can talk more about the correlation between FPRE and predicting eGFR and FSGS. And so if FDA extrapolates and predicts based on your FPRE results, can we assume the extrapolation will indicate eGFR falls into the approvable scenario? Or what else could influence that prediction?
Sure. Well maybe I'll have Noah talk a bit about some of the existing data in those cohorts that he mentioned to support the development of FPRE. But I would say that, you know, from a regulatory perspective, we're going to need to continue to meet with them and make sure that we understand what their needs are for data, understanding that they will be looking at FPRE, looking at longer term eGFR, and certainly assuming that they will evaluate the totality of the data. As Noah mentioned, the eGFR data at this point is not a mature endpoint. It's an one hundred and eight week endpoint that is meant to serve the basis for the confirmatory approval.
Noah, do you want to share a little bit more about how, you know, we're thinking or maybe Bill on the way that regulators might be looking at eGFR?
I can go ahead and get started, Bill, if you want to follow in. So just, you know, FPRE, as you alluded to, is really a very relevant endpoint given its clinical meaningfulness to kidney survival. So it's been linked in, you know, databases in a number of studies to improvement in outcomes and stabilization or improvement in eGFR. So you know, it's something that across renal diseases has been shown, but also within FSGS. Bill maybe I'll turn it to you for the regulatory perspective.
Certainly. I think that thanks, Noah. We believe that the FDA is very engaged in the glomerulonephropathy space at looking at the linkage between proteinuria and effects on eGFR, preservation of eGFR based on a reduction in proteinuria. This is evidence based on their interaction with joint workshops with EMA and the National Kidney Foundation and publications that they participated in. So I think that, you know, the field as a whole, is on the same page here and is enthusiastic about this as a way to provide a tractable development path for innovative therapies in nephrology.
Got it. Okay. Thank you very much for taking my questions and congrats again. I'll hop back in the queue.
Thank you, Maury.
Your next question comes from the line of Michelle Gilson with Canaccord Genuity.
Hi. Congratulations and thank you so much for taking my question. You indicated that you're intending to pursue an accelerated approval submission. Is it safe to assume that results are generally in line with what you've previously discussed with the FDA, or are your plans to reengage regulators to discuss anything specific in the data set that
you've observed?
Good morning, Michelle, and thanks for your question. So we are confident in the interim proteinuria results, and that they can support accelerated approval. And as we have been, we'll continue to engage with regulators to make sure that we understand what data analyses they would want to see from this trial, given that it's ongoing. And that the evidence we have now is based on a surrogate marker for the longer term endpoint. And so, you know, we will look to understand and meet their expectations in our file.
And, you know, certainly those would be planned meetings that we have in the first half of this year.
Okay. And if I could just one more. It looks like the placebo arm outperformed, you know, some investor expectations. I'm just curious if, what you saw in these results on the proteinuria changes or evolves the way that you think about the study in IgA nephropathy at all.
Yeah. So Michelle, that's right. The one thing that I will say is that it was an active control. So irbesartan, not placebo. I'll ask Noah to give his perspective on how it performed.
Yeah, thanks Michelle. As we've shared previously, we knew there was limited data for irbesartan FSGS. And this is the first long term study that includes Urbisartan and FSGS. So we're learning about this in sparsentan over time. Having said that, we accounted for this level of response in FPRE.
Notably, despite the increase in FPRE in the irbesartan arm, we saw a clear difference between arms. And sparsentan showed a statistically significant response. You know, FPRE is a clinically meaningful endpoint, and we are encouraged by the forty two percent response for patients treated with sparsentan after thirty six weeks.
Thank you. And congratulations again.
Thank you. Your
next question comes from the line of Joseph Schwartz with SVB Leerink.
Good morning. Congratulations on the positive data. I was wondering if you've had the opportunity to look at the proportion of patients that were able to get to other remission thresholds like complete remission and tied in with that, you know, if you've been able to, analyze, you know, the impact of or the benefit of higher doses, towards achieving that or FPRE?
Joe, good morning. And thank you for your questions. And I'm going to reinforce that we're just not going to be able to comment on any of the additional analyses that have or will be conducted in this interim analysis. We really want to ensure that we're not introducing any bias to the trial. So I recognize that we're asking for your patience in this.
But certainly we will be looking at a number of different measures of efficacy in this study. But importantly much of that will be once the study is fully completed. No anything further that you would like to add?
No, I think the key here really is, you know, we're charged with the thirty six week FPR endpoint, and that's what we've reported out. Obviously, we'll continue to look at additional analyses potentially for the submission. But at this time, you know, that's what we're comfortable with. We don't want to do anything, as we said earlier, to impute or bias the results and want to make sure to maintain integrity of the study out to the full one hundred and eight weeks.
Right. That's very understandable. I appreciate that. Thanks. And then just based on your prior discussions with the FDA, how much of a trend towards showing a positive eGFR benefit do you think that they want to see in order to grant the go ahead to file for accelerated approval?
You know, how strong does the trend need to be? Is it sufficient do you think as long as it doesn't go against the drug, in a more neutral scenario? Or do you think that they would like to see any degree of positive impact on GFR given the limited amount of data that's going to be available?
Thanks, Joe. So I would let me put it perhaps this way, that we will continue to understand how they want to see these data, you know, as they are limited and interim based on a longer term measurement. And so I would say there's not a specific threshold at an interim look at this endpoint. But again, this is part of why we want to make sure we continue to have dialogue with FDA and EMA to understand, you know, what data they would
like
to see in the submissions.
Makes sense. Congrats again.
Thanks, Joe.
Our next question comes from the line of Tim Lugo with William Blair.
Hi, congratulations on the impressive results, especially around managing this trial through COVID. It's very impressive. One question though. Can you discuss maybe the slope of effect at earlier time points such as week eight, sixteen, 24 and if those earlier time points were in line with what we saw at DUET in the OLE?
Thanks, Tim, and good morning. So maybe I'll ask Noah to talk a bit about, that. But let me just reinforce that we're not going to be able to share any further data from this trial other than the week thirty six analysis on FPRE. Again, we want to make sure that no patient can look at their individual data and unintentionally blind themselves. Noah, anything further you'd want to add and perhaps, you know, inferences from DUET rather than DUPLEX?
Yeah. That's where I was going, Eric. You know, I think that, you know, let me start. We're encouraged by what we've seen in the first cystic analysis. And we can't speak to specific trends in DUPLEX, but I think, Tim, to redirect you back to Duet, I think we've got a pretty good idea of how this drug behaves.
It's well characterized. We've gone out to six years and published the recent forty two point five month median, analysis. So I think I would just earn your attention there. That's not unexpected for us in DUPLEX, but I can't speak directly to the data. And as I said earlier, the top priority is really to maintain conduct and not bias.
Understood. Thank you for the color. Can you maybe speak a little bit of just generalizations around the side effect profile in the PR interim safety look to be comparable, but could you talk maybe about some of the serious side effects that came up and were those relatively balanced between arms?
Yeah. I I can take that one. You know, Tim, again, for the reasons we cited, not won't be speaking to specific AEs, but looked across a number of different avenues, including, you know, some of those that you mentioned. And we are encouraged by these interim results from the study to date, you know, indicating that, you know, SPAR has a comparable safety profile at this current time in this ongoing study to the comparator to irbesartan. I'll also add that, you know, we just completed a fifth data monitoring committee meeting.
And they, of course, have access to unblinded data. And they gave us the green light to proceed as planned. And, you know, we're of course monitoring adverse events, serious adverse events, EOIs carefully as we continue on with the study.
All right. Thank you for that. And again, congratulations.
Thank you, Sam. Thanks, Sam.
Your next question comes from the line of Lisa Bayko with Evercore ISI. Hi, congratulations on the data. A couple additional questions from me. First of all, can you speak to the balance and use of background meds like steroids and immunosuppressives? Are you comfortable with, with how how they look at baseline?
No. Why don't you take that one?
Yeah. We're we're not guiding, as you said, to any specifics on baseline. But we can say that in general, we published the thirty six week with the knowledge that, you know, the groups were balanced in general at baseline between groups with regard to, you know, demographics and background treatments. Of course, we'll do a much deeper dive for the NDA, but, you know, we're encouraged by the results. And I think we're, you know, seeing that balance between groups.
Okay. In the DUET study, there seemed like there was a, greater treatment differential over irbesartan in the more mild patients. What are you seeing here with respect to kind of, the above three grams versus below three grams in terms of kind of treatment benefit? Is it is it pretty much the same despite severity, or are there some nuances there
in terms of Yeah.
What I can say is, we're not we're not gonna be guiding to specifics and specific subgroups, but we did mention on the previous call that the baseline characteristics in DUPLEX are similar to DUET with regard to UPT. And so I'll just say that, you know, we're very pleased with the forty two percent achievement of response for FPRE with the baseline close to DUET. Imagine there would be a significant number of patients above and below that threshold. So that contribute to that overall effect.
Okay. Did you actually just to to to ask a little bit more about eGFR, and I know you can't comment, but did did you look at it yourselves at this interim? Just trying to get a sense of if there was alpha spend on this on this interim on term in terms of eGFR.
So as we discussed previously, the hierarch the statistics were hierarchical. Maybe I'll ask Bill to talk a bit about that.
Certainly. The way the interim is structured in the statistical analysis plan with positive data on FPRE, that is statistical significance which we've achieved in this interim look, all of the alpha now flows to the confirmatory endpoint of eGFR slope at 108. So we don't have, an alpha spend penalty, for taking the interim analysis.
Okay. Interesting. And then I I guess what I was trying to understand is did you actually take a look at eGFR on a unblinded basis at this
though I know you're not
gonna disclose it because you wanna keep the study blinded? I understand that. I'm just wondering if that's something you took a look at.
So, Lisa, our focus at this point was the thirty six week FRE endpoint and key safety data, and we will continue to, assess the interim data in line with expectations from regulators. And so much of what we will be doing in the coming months is precisely that. And that will also be informed by the plan meetings that we have with regulators.
Okay. Can you maybe talk about your timelines to file here? And then as you file, will you be filing on data that's kind of maturing over time and so, you know, the kind of future readouts may be different than today? And maybe you could talk about then kind of trends you're seeing on proteinuria and such. Thanks.
Sure. Bill would you like to take that?
Certainly. Well we believe that the agency is very engaged and interested in bringing these new treatment options to patients. And we're in a good position to engage and have planned interactions as we've stated in the coming months. From a timing perspective, we're continuing to work on preparing the NDA and CMA applications in parallel. And we expect to submit those in the second half of the year pending, regulatory interactions, to really align on how they want the data presented.
We're committed to providing updates, following those regulatory interactions which is our custom.
Okay. And then will you be I guess when you file will you be filing on kind of data that's evolving or just exactly the cut you saw today? And then if it's data evolving, can you maybe talk about any trends you're seeing on proteinuria as you kind of look at that out at patients who've gone out farther? Next. That's my
first question.
Yeah. Yeah. No. Understand the question. Taking the first half of the question, we'll be presenting analysis of pretty much all of the data.
And we'll be working with the agencies on how they want that presented. As far as trends, I'm not going to speak to trends today on what we're seeing for, the reasons we've stated.
Yeah just to add one thing, Bill, Lisa, your question. We did get an immature early look at eGFR. And as Bill alluded to, the data's not mature yet, enough to really analyze, to just ensure there was nothing concerning in terms of any safety trends or any concerns along those lines. And I think we're confident there. To Bill's point, as we evolve that data grows and its information fraction, I think we'll be more comfortable commenting.
And it's part of obviously the full dataset. And that's why we're not discussing to ensure we don't bias and keep patients in the study and ensure the integrity of the study.
Okay, good. That's great. Thank you for that clarity and congratulations again.
Thank you, Lisa.
Your next question comes from the line of Geoff Meacham with Bank of America.
Hey guys. Congrats on the data and thanks a lot for taking the question. Just had a quick one. If if the look at the patients, you know, that were maybe nonresponders or or even hyperresponders, are there any themes that you can tease out among that? I'm just trying to think of, you know, things that could interfere with effect like background therapy or disease progression or things of that nature.
Noah, do you want to take that one?
Sure. Jeff, it's a good question. I think in the frame of, you know, we can't really discuss any more specifics. I'll just say that, you know, if you look at DUET, I think we did publish some data then that showed that regardless of background, steroid therapy, above and below, EPC, and a number of other factors, race, etcetera, demographics, we were able to see results in those populations, pediatric, etcetera. So I think the drug does appear based on the DUAD.
We've got that long term data set to demonstrate an effect in a broad population. But specific to DUPLEX, you know, we just can't call it any further.
Okay. And then just last one. I I know you guys are are going to have a, discussion with, you know, with with FDA and with regulators. Maybe just help us with, you know, going into the the interim. Was there any sort of metric or effect size that, you know, they prospectively had discussed?
Or was it just the interim based on your protocol?
Bill I'll have you take that one.
Certainly. The interim analysis has been based on the achievement of FPRE. And that's been the agreement for what we will be bringing in our submission for accelerated approval both for the US FDA and for the EU. There isn't, I think as you describe it a specific metric or effect size that's been delineated. But ultimately it needs to be, and I think we've covered this some in the past, really a look at the totality of the data.
You have a surrogate endpoint that's predicting or thought to predict ultimate effect in the confirmatory endpoint. And the regulatory agencies want to be they want to have confidence that the effect that they are seeing is reasonably likely to predict success at the outcome. And so they will be looking at all available data to assess that question.
And Jeff, let me add that
we believe that FDA understands the unmet need in this space. And we are confident based on the proteinuria results that we have to date, and our ongoing dialogue that accelerated approval is that can be supported by these data. And of course we want to make sure that our ongoing dialogue reflects their thinking and their expectations. And we believe that we'll be able to get this across the line. And we'll continue to prepare for those files.
And we believe based on any regulators desire to see the full study completed, maintain as Noah says, the high focus on the quality and completeness of the study.
Okay, great. Thanks a lot guys and congrats again.
Thanks Jeff. Thanks Jeff.
Your next question comes from the line of Laura Chico with Wedbush Securities.
Hey good morning guys. Congrats on the data. Thank you for taking the question. I guess I just wanted to follow-up and I'm sorry to continue on this line. We're getting a lot of questions obviously related to the EGFR data.
And I guess I just wanted to clarify, if the accelerated approval filing submission is largely based on FPRE, I guess what is giving you confidence to move forward with that submission? Or is there other are there other elements beyond eGFR that are really more important here to focus on? I guess I'm just trying to understand basically what gives you confidence that things are trending in the right direction at this point?
Thank you, Laura, for the question. And yes, we are confident that the data that we have from the interim proteinuria results can support accelerated approval. And, you know, as we discussed previously, we do recognize that regulators are going be looking not just at those data, but also in the totality of evidence, particularly given that FPRE is a surrogate marker of longer term endpoints. And that longer term endpoint of EGFR isn't yet mature. And we think that regulators recognize that.
And that's why we believe this engagement with regulators is so important so that we understand how they want to see the data, what type of data they see, and that we ultimately can meet their expectations for the interim data and ultimately, you know, in the confirmatory endpoint. And so, you know, I think that we are in a good position. But, you know, we've got to continue to see the study through. And that I think is going to be a high priority for regulators as well. You know, of course there's no guarantee.
But it's going to come down to the quality of the file and ultimately ensuring that we have a study that is conducted with the highest level of integrity. And then it'll come down to a review decision. But what we see today, we're confident in our path forward.
Okay. Thank you, Eric. That's helpful. And I guess one last follow-up. Can you just remind us at this point how many more DMC assessments we should be expecting for DUPLEX?
And then in terms of kind of what would constitute a safety event that would warrant pausing the study or pausing dosing, Could you give us an example of an event that would necessitate kind of having that trigger occur? Thanks.
Noah, do want take that?
Yeah, I can answer that. I just want to follow on to previous question too, just to say that what's also important, and I think it ties into your question, is the safety data. And I think we've seen balance, you know, between groups, which is very encouraging for us. It's a well characterized mechanism. You can see, again, back to the data out to six years in DUET, the long term follow-up, we know how the drug works.
We understand, you know, their AEOIs. We're following those very carefully. And, again, patients are tolerating the drug quite well. You know, physicians are comfortable. You know, so I think that's the key.
Also just point out that this is a heavily pro neurotic disease. Physicians, when they target an approach in practice, they will try to treat proteinuria down as low as they can get, because they realize that proteinuria is directly toxic to the kidneys. And that's really the basis of the FPRE, right, is that the proteinuria endpoint itself is clinically meaningful. And there really aren't good options out there. I think Eric alluded to that in his opening.
There are drugs that are either limited in their efficacy, or they've got long term side effects of the IST. So having a non IST achieve a forty two percent reduction, just to summarize, in a disease with a high unmet need of proteinuria disease, where half these patients on average are going to dialysis within ten years, I think it's pretty important data in light of seeing a drug that is safe and will continue to follow these patients long term. To your question about the DMC, we don't typically guide in their driven proposal. But I think it's encouraging that we had this stiff meeting. They see completely unblinded data, and they've given us the green light to move forward.
I think we'll continue to follow the study. Your question about what event would occur, that's really a DMC question. I mean, that's the type of information that they're evaluating. If you're asking me as a clinician, I would say if you saw some very surprising event that came in with some frequency, either something very serious or with frequency, you know, that was unexpected, it would have to be looked at carefully. But I think we're in a really good place.
I think, again, I'd point to DUET out to six years. We published all that data. We're in a quite unique position in having that long term data set to point to 600 plus patients, again well characterized. So hopefully that addresses to some degree your question.
Yes it does Noah. Thank you guys. Congrats.
Thank you Laura. You.
Your next question comes from the line of Do Kim with BMO Capital Markets.
Hi, good morning. Thanks for taking my questions and congrats on the data. I guess my first question is when you look at the FPRE results at this interim analysis, how do you think about the assumptions that you made for the eGFR confirmatory endpoint and the statistical powering around that, did you account for this level of difference in FPRE?
Yes. So Joe, good morning, and thanks for the question. These results are consistent with our assumptions and our powering. And so we were pleased to see the results thus far. And I think, you know, we are our focus is that, eGFR will also play out and is well powered.
That is a longer term endpoint. That's why you'll hear us continue to repeat that we've got to make sure that we maintain the blind and keep these patients in for that full one hundred and eight week measurement.
Great, thank you. And as we think about the IgA nephropathy data in the third quarter, are there any takeaways that we could look at the FSGS proteinuria data and apply it to the upcoming IGAN trial?
So I'd say that we're encouraged by the statistically significant response in FPRE with DUPLEX. And we think that it supports the hypothesis that sparsentan can meaningfully reduce proteinuria for patients with rare kidney disorders. And so we think it does build further confidence that sparsentan can be effective in IgA nephropathy. But I want to point out that these are different trials. They're different diseases.
And so our focus is making sure that we conduct that trial well. And, you know, reinforce that the mechanism addresses a common pathway between the diseases. And so we're confident, but we've got to wait until quarter three to see those results.
Okay. And then last question. Could you comment on how the dose titration worked
in this study?
Did it did it go and prevent the dose interruptions and reductions that you saw in the phase two?
Noah, why don't you take that one?
Yeah. Good question. So we had looked at that in an unblind sorry, in a blinded manner previous to unblinding, and I think we had reported that the two week titration was allowing patients to get to that higher dose. And so no reason to change that statement. And again, we'll continue to, you know, analyze the data and follow these patients.
But we feel confident that that titration step was an important chain between DUET and DUPLEX, given the blood pressure related side effects that we saw in DUET.
Got it. Congrats again and thanks for taking my questions.
Thank you, Joe. Thanks.
Your next question comes from the line of Lisa Bayko with Evercore ISI. Hi, thanks for taking the follow-up question. I just wanted to ask, in your conversations with FDA, does it seem like FDA is well informed with kind of, you know, a temporary dip due to, you know, initiation of therapy, a temporary dip in eGFR, which is actually seems to be a good thing versus a sort of change in slope over time that can be an indication of kidney worsening. So a change of slope in eGFR versus a kind of temporary dip due to initiation of therapy. Is that something that, you know, kind of FDA is aware of?
Can you maybe speak to how informed and educated they are on this point? And it's a point that was kind of like well articulated with a KOL call we hosted earlier this week. And so that's why I'm just following up to ask. Thanks.
Sure. Thank you for the follow-up question, Lisa. I'll provide my comments and ask Bill to provide anything further. You know, I think that the acute hemodynamic effect is well understood for these classes of medicines. And I think, you know, would imagine, I certainly don't want to speak for the FDA, but that it would be well understood that the blood pressure lowering effect of sparsentan could be associated much like we saw in DUET with that acute hemodynamic effect.
And there are other classes of drugs that don't have that acute effect. But I think as you point out, our understanding and the broad nephrology community's understanding is that that is, it's well understood, and it is not deleterious to the long term renal health of the patient. Bill, I'll ask you to speak anything further with regards to the regulatory perspective.
Certainly. It's a great question, Lisa. The folks on the other side of the table both at The U. S. Regulatory agencies and in Europe are really very well versed in nephrology as well as trial design.
And they do understand the physiology of drugs that present with a reduction in blood pressure and then the concomitant transient reduction in eGFR. They understand the nature of it. They're well versed in this. And it's been a focus of some of their work externally with the National Kidney Foundation and with academic groups studying just how do you run trials when you have a physiology or a pharmacology of the drug that creates an intermittent confounder to the overall confirmatory variable? I think part of the reflection of that is the duration of the study.
You know, a two year endpoint allows for what, you know, a readout that would be immature at thirty six weeks to mature and to allow things to stabilize and get a true read on, the comparison of the efficacy of the agents. And I think that, is reflected in the study design and those discussions that we've had for quite a while.
Great. Thanks for that. And there are no further questions at this time.
Great. Thank you Lisa. And thank you all for joining us on short notice this morning and appreciate the quick pulling together to talk about the promising results from the DUPLEX Study. We look forward to speaking with you in the near future as we continue to make our progress and also when we report full year results later on this month. Thank you again and have a great rest of the day.
This concludes today's conference. You may now disconnect.