Retrophin (RTRX) Q4 2019 Earnings Call Transcript

Retrophin (TVTX -5.05%)
Q4 2019 Earnings Call
Feb 24, 2020, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good afternoon, ladies and gentlemen, and welcome to the Retrophin, Inc. fourth-quarter/full-year 2019 financial results and corporate update conference call. [Operator instructions] As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr.

Chris Cline. Please go ahead.

Chris Cline -- Vice President, Investor Relations and Corporate Communications

Great. Thank you, Angela. Good afternoon, everyone, and welcome to Retrophin's fourth-quarter and full-year 2019 financial results and corporate update call. Today's call will be led by our chief executive officer, Dr.

Eric Dube, and will be joined for the prepared remarks by our chief medical officer, Dr. Noah Rosenberg; and our chief financial officer, Laura Clague. Peter Heerma, our chief commercial officer; and Dr. Bill Rote, 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, 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 Form 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, February 24, 2020, and Retrophin 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?

Eric Dube -- Chief Executive Officer

Thank you, Chris, and good afternoon. I am incredibly proud of our team at Retrophin and our accomplishments for 2019. Specifically, we continue to identify and reach new patients with our commercialized products, including through the successful launch of our new formulation of THIOLA, and we continue to advance sparsentan in our two pivotal Phase 3 studies. We also made the difficult but prudent decisions to move beyond programs that did not meet our criteria for advancement.

This includes discontinuing our development activities for the L-UDCA program and declining to exercise our option under the Censa collaboration. It also included ending further development of fosmetpantotenate following the disappointing results from the FORT Study. Notably, these actions allowed our organization to come together with a clear focus and make significant progress on the key priorities that we believe will position us to become a leading company dedicated to the delivery of innovation and hope to patients in the global rare disease community. Maximizing sparsentan's potential for patients with rare kidney disorders remains our highest priority.

For the last 50 years, clinical trials in nephrology has been too few and those in rare nephrology have been nearly nonexistent. With sparsentan, we are changing that. Our DUPLEX and PROTECT studies are viewed as landmark trials that have the potential to change the treatment paradigm for FSGS and IgA Nephropathy. If successful, they have the potential to deliver the first medicine approved for these rare disorders and the prospect of impacting the more than 100,000 currently underserved patients living in the U.S.

and Europe. This is why our primary near-term focus is executing on the enrollment of our pivotal studies as quickly as possible while maintaining the high-quality conduct of the trials we have seen since initiation. I am pleased to report that as a result of our clinical and operational team's solid execution over the last several months, we are well on our way to reaching the enrollment milestones that will enable top-line read-outs from our pivotal studies. In DUPLEX, we are approaching enrollment of the 190th patient with FSGS to enable the 36-week proteinuria analysis.

We anticipate reaching this milestone in the next two months, which keeps us on track to report top-line data in the first half of next year and, if positive, submit our regulatory filings for approval in the U.S. and Europe. We also made substantial headway with enrollment of our pivotal PROTECT study of sparsentan in IgA nephropathy. We have leveraged our learnings and synergies from the DUPLEX study to create a high awareness and growing enthusiasm among investigators and patients for the PROTECT study.

This has resulted in a meaningful inflection point, which gives us great confidence in achieving our enrollment target by early next year to support the top-line data from the 36-week proteinuria analysis in the first half of 2022. We clearly have positive momentum for enrollment in both of our studies, and we look forward to updating you as we reach key milestones later this year. As part of our priority to explore opportunities to maximize sparsentan's potential to help patients, we've also continued to evaluate additional development opportunities. As we mentioned on our previous call, we have seen encouraging preclinical, exploratory work in Alport syndrome.

Our team continues to make progress in evaluating clinical feasibility, and we anticipate making a decision later this year on whether to pursue an additional indication. Our main priority alongside sparsentan's advancement is to build upon our strong commercial teams' capabilities. We are focused on this so that we may optimize the full potential of our approved products and ultimately prepare for a successful launch of sparsentan. In addition to our clinical and R&D teams, I continue to be impressed with the execution of our commercial organization.

A successful commercial stage rare disease company must have a foundation built upon earning and keeping the trust and respect of the patient communities, and it must have a deep understanding of who the patients are, what is most important to them and their families, as well as where they are on their treatment journey. This is how our organization has continued to identify new patients and deliver our life-changing therapies. We continue to have a successful launch of THIOLA EC, and it serves as a good example of how we have listened to the needs of our patients. Prior to introducing the new product to the market, our market research told us that approximately two-thirds of cystinuria patients would ultimately choose the new EC formulation, because it provided the potential for freedom of administration and potential to reduce the number of tablets necessary to manage their cystinuria.

I am pleased to report that within six months of making THIOLA EC available, we have reached that mark. This demonstrates our ability to understand patients and their needs, to execute a launch plan and to identify new patients, including by reengaging those who have previously discontinued therapy. Additionally, it gives us a high degree of confidence that we have a robust foundation in nephrology to launch sparsentan, if approved, and that we will be able to maximize its potential for patients. We also continue to have solid execution with Cholbam, where our goal is to help patients manage their bile acid synthesis disorders or liver disease from Zellweger spectrum disorders.

Our efforts with specialists, including pediatric geneticists and hepatologists are resulting in the identification and treatment of new patients with these ultra-rare conditions. Chenodal also continues to grow. And we recently initiated clinical development that may ultimately lead to an NDA to support a label for CTX. Noah will talk a bit more about that shortly.

Our final priority is to evaluate opportunities to diversify our growth potential through business development. We continue to look opportunistically within the rare and ultra-rare spaces. Importantly, we will remain disciplined to only act on transactions where we believe we can leverage our current expertise to create meaningful value. Let me now turn the call over to Noah for a clinical update.

Noah?

Noah Rosenberg -- Chief Medical Officer

Thanks, Eric, and good afternoon. Sparsentan has the potential to be a first-in-class therapy and shape the treatment paradigm for patients with FSGS and IgA nephropathy. The goal of our ongoing pivotal DUPLEX and PROTECT studies is to ultimately deliver sparsentan as a potential first medicine approved for these rare kidney disorders. As Eric mentioned, the awareness and enthusiasm for these programs continues to rise, which is in part due to broad support for proteinuria and eGFR measurements serving as clinical endpoints and glomerular disease like FSGS and IgAN.

We also hear from investigators and thought leaders in this space that sparsentan has a well understood mechanism with an established safety database of more than 500 subjects. And that our Phase 2 DUET study, one of the largest FSGS trials conducted to date, provides confidence in sparsentan's potential to impact disease progression. In the DUET study, the overall sparsentan-treated group demonstrated a significant reduction in proteinuria and a clinically meaningful response in the FSGS partial remission of proteinuria endpoint or FPRE. This is the 36-week endpoint in DUPLEX to support potential FDA and EMA submissions next year.

After eight weeks in DUET study, we also saw that 28% of the sparsentan-treated patients achieved the FPRE endpoint, a threefold increase when compared to irbesartan. Importantly, we saw an increasing proportion of patients achieving FPRE during the 84-week open-label period, including nearly 50% of sparsentan-treated patients qualifying as responders at 36 weeks. These components, along with an efficient network of sites and scientific engagement have fueled the momentum in both of our pivotal studies to end 2019 and begin the new year. As you have just heard, both our DUPLEX and PROTECT studies are enrolling well, and we are maintaining high-quality study conduct.

This is a testament to the collective hard work of our entire organization and partners. Enrollment in our lead pivotal study DUPLEX in FSGS continues to benefit from a heightened sense of awareness and engagement in a broad global network of open sites. We have designed DUPLEX to recruit a similar patient population to our DUET study, and thus far, the baseline characteristics of the enrolled population remain consistent with our expectations and how the study was powered. Our most recent months have produced some of the strongest screening and enrollment trends yet.

This gives us confidence in reaching 180 patients enrolled in DUPLEX in the next two months and keeps us on track to report top-line results from the 36-week proteinuria analysis in the first half of next year. The proteinuria analysis will measure the proportion of responders that reach FPRE after being randomized to either sparsentan or irbesartan for 36 weeks. Importantly, if sparsentan shows a statistically significant improvement in response rate in DUPLEX, we would expect to then file a new drug application under the Subpart H accelerated approval pathway in the U.S. and for conditional marketing authorization consideration in Europe.

To ensure we're in a position to file for approval after receiving top-line data, our teams are conducting regulatory submission planning in parallel. We also made noteworthy progress recently with our PROTECT study in IgA nephropathy. We continue to leverage the established nephrology footprint built by the DUPLEX study, the heightened awareness of IgA nephropathy and the larger overall patient population to accelerate recruitment. We have maintained momentum in the study including through the holiday period, which has resulted in some of the highest recruitment months to date.

As a result, we are very confident in our ability to meet the enrollment milestone of 280 patients in PROTECT by early 2021 and to report top-line results from the 36-week proteinuria analysis in the first half of 2022. The proteinuria analysis in PROTECT will be the percent reduction of proteinuria after being randomized to either sparsentan or irbesartan for 36 weeks. It has been widely established that proteinuria exposure over time is one of the strongest predictors of renal function decline in IgA nephropathy. Thus, if we are successful in demonstrating a meaningful difference in proteinuria reduction between sparsentan and irbesartan after 36 weeks in the PROTECT study, we would expect to then file an NDA under the Subpart H accelerated approval pathway in the U.S.

and for CMA consideration in Europe. As we move through 2020, we will channel the momentum in our two pivotal programs to continue our pioneering efforts with the goal of potentially delivering the first medicine approved for FSGS and IgA nephropathy. Our focus remains on completing enrollment in both studies and preparing for our subsequent FDA and EMA filings. Last, before I turn the call over to Laura for the financials, I would like to point out that we've recently initiated a small pivotal study, evaluating the efficacy and safety of our approved product Chenodal for the treatment of CTX or cerebrotendinous xanthomatosis.

As many of you may know, Chenodal is not labeled for the treatment of CTX, and we do not promote the product. Over time, we've been working toward the path that will potentially allow us to gain an updated label. Our hope is that this study will ultimately lead to a CTX indication and allow for us to support greater identification and earlier treatment efforts in this ultra-rare, progressive neurological disorder. Let me now turn the call over to Laura for the financial update.

Laura?

Laura Clague -- Chief Financial Officer

Thank you, Noah. During the fourth quarter, net product sales from our commercial portfolio grew to $46.7 million, a 7% increase over the same period in 2018. For the full-year 2019, we reported $175.3 million in net product sales. This achieved our guidance and represents our fifth consecutive year of organic growth.

We reported a GAAP net loss of $30.3 million for the fourth quarter and $146.4 million for the full-year 2019. After adjusting for noncash expenses and income tax, we reported a non-GAAP net loss of $11.2 million for the fourth quarter and $89.9 million for the full-year 2019. On a GAAP basis, R&D expenses were $36.4 million for the fourth quarter and $141 million for the full-year 2019. The increase over 2018 is largely attributable to higher expenses to support our clinical and product development efforts.

On an adjusted basis, R&D expenses were $34.5 million for the fourth quarter and $132.9 million for the full-year 2019. Relevant noncash expenses for the fourth quarter included $1.9 million of stock-based compensation and amortization. On a GAAP basis, selling, general and administrative expenses for the fourth quarter were $27.5 million and $129 million for the full-year 2019. The increase over 2018 is largely attributable to increased compensation expense and higher professional fees.

On an adjusted basis, SG&A expenses for the fourth quarter were $19.6 million and $95.5 million for the full-year 2019. Significant noncash adjustments for the quarter consisted of $7.9 million in stock-based compensation and depreciation and amortization. Looking ahead for the year, we anticipate that our net product sales will continue to grow in the mid-single-digit range, similar to what we experienced in 2019. As has been typical for us in years past, we anticipate seasonality in net product sales, including higher gross to net discounts during the first quarter of the year.

We do expect that to normalize throughout the balance of 2020. We anticipate that our operating expenses for the full-year 2020 will be similar to what we reported for the full-year 2019. This includes ongoing disciplined investments to achieve our enrollment and development milestones for our Phase 3 studies. We entered the new year with a solid financial foundation and $398.5 million of cash and cash equivalents as of December 31, 2019.

Importantly, we believe that we have sufficient cash on hand to fund our operations beyond our Phase 3 data readout. Let me now turn the call back to Eric for his closing remarks. Eric?

Eric Dube -- Chief Executive Officer

Thank you, Laura. The outlook for our organization is clear, and as a result of our dedicated team members' hard work and accomplishments, we are in a great position to build upon our momentum in 2020. We are fortunate to hear directly from the communities we aim to serve, including in the case of a renal pathologist, who is living with IgA nephropathy. He recently shared with us that he has been hoping and waiting for a medicine that could meaningfully improve treatment options for rare kidney disorders for many years.

For him, it is not just about his patients. It's also personal, hearing stories like this gives us a deep understanding of the unmet need and provides an incredible sense of urgency for all of us at Retrophin. We will channel this urgency throughout the year to remain focused on the execution and advancement of our pivotal DUPLEX and PROTECT studies so that we deliver top-line data and potential FDA and EMA filings next year. In parallel, we will continue to deliver our commercial products and build upon our commercial capabilities so that if approved, we are in a position to quickly reach the greatest number of patients with sparsentan.

Let me now turn the call back over to Chris to open it up for questions. Chris?

Chris Cline -- Vice President, Investor Relations and Corporate Communications

Great. Thanks, Eric. Angela, can we go ahead and open up the lines for Q&A, please?

Questions & Answers:

Operator

Yes, of course. [Operator instructions] And your first question comes from the line of Joseph Schwartz with SVB Leerink. Please go ahead.

Joseph Schwartz -- SVB Leerink Partners -- Analyst

Great. Thanks so much for taking my question, and congrats on the progress. Several sessions at ASN during the fourth quarter highlighted a significant amount of interest in new treatments for glomerular disease among the treatment community, so I was wondering if you could just summarize your main takeaways from the sessions. And do you have any new insights on where sparsentan could fit in?

Eric Dube -- Chief Executive Officer

Thanks, Joe, for the question. Let me start, and then I'll ask Noah to weigh in. I think importantly, what we saw at the most recent ASN was a growing body of evidence to support the link between proteinuria and eGFR, particularly within IgA nephropathy and rare renal diseases, which gives us great confidence in how we have designed our studies. Noah can share a little bit more about what he saw from ASN.

Noah Rosenberg -- Chief Medical Officer

Yes. I think, Eric, I would just support your statement about the emphasis on proteinuria. And I think that's probably, Joe, what's really spurred a lot of interest in the area. The nice thing about where we are at this stage is, in FSGS, in particular, we're in Phase 3.

There are no other programs in Phase 3, and we're pretty far ahead of the pack. I think we've got an established database. From a safety standpoint, the drug is well accepted and well understood. I think the other advantage that we have is that we're non-IST, meaning that we're not in immunosuppressive therapy.

As you probably noticed, quite a bit of interest in the area or in areas of complement in different immune suppression, steroid-sparing approaches, but many of these approaches have not yet been proven from a safety standpoint. And while, of course, we hope that they are successful to bring new cures to patients because they direly need it. Number one, they still have to be proven in terms of both efficacy and safety. And number two, I would say that there really wasn't anything out there, Joe, that I could see that we really couldn't necessarily be complementary to given the way the drug works.

So I think it further supplements the arguments that there's a role for sparsentan not just when we get there, which is probably first, but also when some of these other therapies potentially get there as well and working together.

Joseph Schwartz -- SVB Leerink Partners -- Analyst

That's very helpful. Thanks. And then as a follow-up, I was wondering if you could talk about the requirement for patients in DUPLEX to wash-out of any RAS blockers other than irbesartan before entering the study. Has this been an impediment for any patients or investigators who might prefer a different RAS blocker than irbesartan? And is this being handled the same way in PROTECT? It seems like it could be different based on the protocol I see online.

Eric Dube -- Chief Executive Officer

Yes. Noah, do you want to take that one?

Noah Rosenberg -- Chief Medical Officer

Sure. To answer or address your first question, in terms of the way that DUPLEX is designed, these patients do go undergo a wash-out period. I would say the majority of the patients that are coming in are on RAS blockade. Because as we know, those patients are often treated with that therapy.

We saw that in DUET, about 85% of patients are on RAS. I think that we've talked frequently with sites and investigators. They've told us from beginning that this is a very recruitable protocol. That specifically was not raised to us as a particular concern.

And I think the reason for that, Joe, recall that sparsentan is a dual blocker, so we've got not only an endothelium blocking component, but an angiotensin blocking component as well. So essentially, it's kind of, in a sense, two drugs in one. The patients who aren't going to be randomized on to SPAR go on to, as you know, irbesartan. So either way, they're going to get an ARB, and frankly, when you look at the data, it's not really clear that one ARB necessarily is superior to another.

They're generally thought of as a class effect, these drugs tend to work pretty uniformly. So I think that's kind of how I would answer that. And then I think with regard to the two studies, while there is a two-week wash-out in DUPLEX, it's a small nuance. But we actually do have in the PROTECT study, the ability to go directly and switch over to SPAR or irbesartan without the wash-out effect there.

There's certainly always debate in these studies, and we've had many, many discussions about what's right and what's the best approach. Frankly, it probably doesn't matter that much. Because the two weeks, once they get into the study, they're just going to switch over anyway, so it doesn't have much of an impact on the overall data set.

Joseph Schwartz -- SVB Leerink Partners -- Analyst

That makes sense. Very helpful. Thank you.

Operator

And your next question is from the line of Maury Raycroft with Jefferies. Please go ahead, sir.

Maury Raycroft -- Jefferies -- Analyst

Hi, everyone. Congrats on the progress, and thanks for taking my questions. I was wondering for Phase 3 DUPLEX, the confirmatory endpoint is change in slope of eGFR after 108 weeks. I'm wondering if you can remind me what exactly is the confirmatory endpoint in Phase 3 PROTECT.

And then for both studies, how important will the results be after the four-week drug cessation at end of study? What are your goals post drug cessation and what will FDA be looking for?

Eric Dube -- Chief Executive Officer

Thanks, Maury, for the questions. Why don't I take the first part around the confirmatory endpoint, and then I'll have Noah talk about the end of treatment measurement. So for both -- sorry, DUPLEX and PROTECT, the confirmatory endpoint is eGFR slope with an interim analysis on proteinuria, and we're confident in sparsentan's ability to have efficacy both for proteinuria and eGFR. With regard to this approach for both diseases, it's very much aligned with the nephrology community and the wide belief in the utility and the link between proteinuria and eGFR and this is supported by the literature and, in fact, a growing body of evidence that supports the link between proteinuria and eGFR.

And it remains a focal point for future use in clinical studies as we've seen both at ASN this past year that we just talked about, but also we think from a regulatory standpoint that there is growing confidence and acceptance of this approach, which we're seeing now reflected in more and more studies using this methodology of proteinuria and eGFR in rare renal trials. For us, it's critical to demonstrate that link in a trial, and we designed our studies to have some flexibility. As is common in studies like this, we have planned a sample size reassessment procedure that would allow us to further derisk the eGFR endpoint if we think it would be helpful. Importantly, if the decision is made to do this, we believe it would not impact the timelines for our proteinuria analysis or subsequent NDA and EMA filings of the proteinuria data.

So overall, that confirmatory endpoint of eGFR we think is well established and for our clinical trials, everything is aligned to make sure that we are successful and so we've got a high degree of confidence in that confirmatory endpoint. Now I'll ask Noah to add anything else and also to address your question around the cessation of treatment at the end of the trial.

Noah Rosenberg -- Chief Medical Officer

Thank you, Eric. So Maury, it's a great question. If you look across, it essentially is a regulatory requirement to stop drug and then measure four weeks off. Frankly, if you look at bardoxolone and some of the other programs, the ADPKD drug from Otsuka, they were required to do this as well.

My sense is that what they're looking for is to ensure that there are no significant, number one, safety concerns and any changes in eGFR off drug. Once you stop drug, there's no dramatic changes there. That probably doesn't apply as much to our therapy, but I think it's a standardization technique that they're probably applying. Again, I'm just intuiting here across programs so they can sort of look from one to the other.

But for us, it's probably not a huge relevant piece.

Maury Raycroft -- Jefferies -- Analyst

Great. That's very helpful. And then I had a question for the Chenodal Phase 3 in CTX. Just wondering if FDA recommended that trial or is Retrophin proactively running in.

And then I see the primary endpoint is changing, urinary bile alcohols week 4 and 16. I guess can you walk through the crossover design for the study?

Eric Dube -- Chief Executive Officer

Yes. So I'll give a brief overview, and then I'll ask Bill to mention it. With the Chenodal program, it is quite unique. And I think it's important to just remind everyone that this is a medicine that has been available for some time and is not approved for CTX but is commonly used for this ultra-rare condition.

And we believe that it was the right thing to do to study this and to get an approval for this and to have a label that would help in guiding our discussions with clinicians at how to use Chenodal in these patients. Bill, do you want to talk about the design of the trial?

Bill Rote -- Senior Vice President of Research and Development

Certainly. The trial is a placebo-controlled, randomized, crossover design with a blinded withdrawal that happens twice during the study. So the way that works, patients who are already on Chenodal, once randomized, go into their first period of blinded withdrawal, and their medication is changed. And the physicians don't know whether it's being changed to placebo or they remain on Chenodal.

And there are observations for clinical symptoms on the part of the patient and the physician. There's also biomarkers that are being assayed, and you referenced the urinary bile alcohol, to see if there are biochemical changes that are evident with cessation of treatment. By having two periods, we repeat the process and just split the treatment selection, that way each patient serves as their own control. And so by using a short window of time for withdrawing the medicine from the patient, we're able to maintain a study that's safe and ethical and hopefully enrollable, that patients will accept, the physicians accept.

But it will give us the data that allows us to demonstrate the utility and support an ultimate regulatory filing to get CTX on the label for Chenodal.

Maury Raycroft -- Jefferies -- Analyst

Thank you very much.

Operator

And your next question is from the line of Gena Wang from Barclays. Please go ahead.

David Hoang -- Barclays Capital -- Analyst

This is David for Gena. Thank you for taking my questions. First question is regarding the DUPLEX and PROTECT trial. Can you remind us the priori assumptions for the trial? And then a follow-up with Maury's question.

So you said that you're planning to do a sample size assessment. Can you just help us understand whether the sample size assessment would actually affect the powering of the trial?

Eric Dube -- Chief Executive Officer

Thanks, David. Noah, why don't you take these questions around powering and then how does sample size modify?

Noah Rosenberg -- Chief Medical Officer

Sure. Thanks, Eric. So let's start with DUPLEX. For the proteinuria analysis of 190 patients, the analysis will evaluate the proportion of patients achieving FPRE at week 36.

So with 190 patients, that gets us power at approximately greater than 90% for the two-sided alpha of 0.05. This assumes that the treatment difference in FPRE response at 36 weeks is consistent with the observed difference at week 8, so the end of double-blind treatment, which was 28.1% with sparsentan and 9.4% for ARB from the sparsentan Phase 2 DUET study. For the eGFR endpoint, we'll be looking at eGFR slope, and that is the confirmatory endpoint to week 108 and the projected treatment difference between slopes was obtained by modeling the relationship between eGFR and FPRE using DUET and the NEPTUNE database. Importantly, what has been observed is that even what appears to be small differences in eGFR slope, such as like -- we use 0.8 to 1.52 as that range.

That small range around one has been considered to be clinically meaningful, so that's kind of how it works for DUPLEX. For PROTECT, the primary endpoint, remember, is slightly different in DUPLEX's FPRE. In PROTECT, it's percent change from baseline. And that's because they utilize separate databases to derive these cut points.

And that is the last -- so for PROTECT, the percent change from baseline, the last pretreatment value available before the first dose of study medication. In UPCR, based on a 24-hour urine collection at week 36, so they have similar time point and similar measure, just a different percent versus absolute. PROTECT is empowered to detect a 30% difference in proteinuria between SPAR and placebo and this is based on two large IgAN registries in Western, Glasgow. And basically, it's showed in these registries that, greater than 1 gram per deciliter change or patients who had greater than one change, who achieved a 30% reduction at nine months with RAS blockade had decrease in long-term eGFR decline.

And consistent with findings from the NKF workshop based on the KHI white paper, a 30% reduction at nine months is also predicted to reflect the treatment effect on outcomes. So you can see we've incorporated multiple ways in these two studies of assessing these endpoints, and they are consistent with the data and literature that's out there. So that was the first question on powering, right? And the second question was sample size.

David Hoang -- Barclays Capital -- Analyst

The sample size, how that might affect powering?

Noah Rosenberg -- Chief Medical Officer

Right. So in terms of how sample size might affect powering, it's hard to put a specific likelihood on either study, whether it would affect the overall endpoint. But remember that this reassessment, which is a de-risking piece, right, which allows us to recalibrate, really is designed to affect the confirmatory endpoint and not the initial proteinuria endpoint, so we don't expect that to impact our primary endpoint, 190 patients and the timeline. We don't have visibility into whether that reassessment will or will not occur.

We'll just continue to monitor the data and monitor our data and externally what's out there. And as we mentioned earlier, if the reassessments result in any change, it would not be expected to impact the timelines for proteinuria, so the time lines that we've been speaking about.

Eric Dube -- Chief Executive Officer

Thanks, Noah. I think just to take a step back, David, from the detailed description that Noah has provided. If we were to adjust the sample size for either of the trial, it would be for eGFR to ensure that we have sufficient power and thus, derisk the trial in demonstrating the confirmatory endpoint. And again, if we do that, it has no bearing on -- or unlikely to have any bearing on our timing for proteinuria and certainly would not impact the power assumptions for that endpoint.

Noah Rosenberg -- Chief Medical Officer

And just, Eric, if I may add one more thing. It is a technique that's commonly used in the area, and there are examples out there, companies have used this in renal rare.

That's helpful. Thank you, guys.

Operator

Your next question comes from the line of Christopher Marai with Nomura Instinet. Please go ahead.

Jackson Harvey -- Nomura Instinet -- Analyst

Hello. This is Jackson Harvey on for Christopher Marai. Now that you have quite a few patients on the Duplex study, I was just curious if you can provide some early color around the proportion of patients that have had to reduce dose due to tolerability and maybe there are reasons for doing so. And my second question is, if the 36-week proteinuria measurement is not statistically significant, but trending in the right direction, will you continue to run the trial for the eGFR endpoint? Thank you.

Eric Dube -- Chief Executive Officer

Thanks, Jackson. Noah, why don't you take these questions?

Noah Rosenberg -- Chief Medical Officer

Sure. Let me start with the DUPLEX question. I think, specifically, you're asking about the progress of the study and dosing and how many patients. And just to reflect back, for those who don't know, the DUET study and DUPLEX were slightly differently designed.

DUET did not have titration step, so everyone started at 200, 400, 800, and there were a number of patients at the 800 didn't tolerate it. They had to back down. We designed the DUPLEX study with a 400 to 800 titration step and that was to allow patients to acclimate to the dose and hopefully reduce any of the safety concerns. Well, it's an ongoing study, and we can't reveal the number.

We do track that, and I can say that we're not seeing any significant safety concerns or safety issues. The drug does appear to be well tolerated. And as you know, we had a recent data monitoring committee meeting, which we mentioned on the last call, that gave us the ability to continue to move forward with the study. And I think that's probably as much as I can say.

Eric Dube -- Chief Executive Officer

Yes, Noah. I think the only other thing I would add before you go to the 36-week proteinuria is, in the DUET study, we did see that there was a significant efficacy difference for the patients that were on 400 or on 800. So Jackson, while the team has designed the DUPLEX study to minimize that early onset RAS blockade-associated adverse events that we saw if those patients do down titrate, we don't believe that that would impact efficacy.

Noah Rosenberg -- Chief Medical Officer

Yes. Can you just repeat the 36-week question for me, the proteinuria question?

Jackson Harvey -- Nomura Instinet -- Analyst

Sure. I'm just curious, if that endpoint misses at 36 weeks, but it follows and trending in the right direction, will you continue the trial to the eGFR endpoint?

Noah Rosenberg -- Chief Medical Officer

Yes, that's a really great question. I would say this, that when the data -- in the first half of next year, when we have that data set, we will look at it, and we'll look at the totality of the evidence at that time. So there could be some circumstance where you might imagine, while we might not hit significance overall, perhaps, you might see a subgroup that shows significant difference. So we try to prepare for all scenarios.

But of course, when you get the data, you get the data and you look at it. And for me, as a clinician, having done many of these studies, it really comes down to do you have clinically meaningful data set that can help patients in the long run. If you look out there in the renal rare space, I mean, you have therapies that haven't necessarily even improved their endpoint and specifically in rare as well, but they're out there and even some therapies that are approved within select subpopulation. So I don't want to speculate on what that might look like, but we internally are always evaluating and looking at these different potential scenarios and we'll certainly update you at that time.

And hopefully, we won't have to cross that bridge and will be not significant.

Jackson Harvey -- Nomura Instinet -- Analyst

Great. And if I could squeeze in one more question, you said DUPLEX demographics are similar to DUET. So does that include the percentage of African American patients?

Eric Dube -- Chief Executive Officer

No.

Noah Rosenberg -- Chief Medical Officer

Yes, yes. Thank you, Eric. We haven't disclosed those numbers. And I will tell you that we've screened quite a number of patients in the study, including African American patients, and we've made all efforts to include as many patients as we can.

And that's really as much as I can say.

Jackson Harvey -- Nomura Instinet -- Analyst

Thanks.

Noah Rosenberg -- Chief Medical Officer

Operator, next question, please.

Operator

Your next question is from the line of Liisa Bayko with JMP Securities. Please go ahead.

Liisa Bayko -- JMP Securities -- Analyst

Hi. I also want to say congrats on progress. And just a couple of questions from me, one follow-up. For this adjustment, is there a particular time frame where you'll be doing that? And is that something you'll communicate to us just letting us know that you've increased the size or that you're proceeding as with no adjustment? Or just curious on that point.

Noah Rosenberg -- Chief Medical Officer

Yes. Eric, maybe you like to answer?

Eric Dube -- Chief Executive Officer

Yes. So Noah, why don't you take that one?

Noah Rosenberg -- Chief Medical Officer

OK. Liisa, the reassessment is based on enrollment trends in DMC scheduling, so we really cannot provide a specific time frame there. As is common in these assessments, any change will be done working with the DMC after reviewing the available data and with regulatory input. So just want to reemphasize, if any of these reassessments occur, they're not likely to have an impact on the proteinuria endpoint.

And of course, once we are confident if such a change were made, we would let you know.

Eric Dube -- Chief Executive Officer

Yes. I think importantly, Liisa, if there was a change, we would make sure that we communicate anything around the timelines that we have committed to. And I think, as Noah and I have mentioned, if we were to do this, it would be on the confirmatory endpoint. And we don't believe that it would have any impact on the proteinuria and the timelines that we've committed to over the next year in terms of proteinuria readout and regulatory filings, but certainly, we will make sure that we provide any update.

Liisa Bayko -- JMP Securities -- Analyst

OK. And it's not a futility analysis. It's just an interim check to see if things are trending in the right direction. And then if any adjustments are needed to highlight those operational bulwarks, OK? And then for the CTX...

Eric Dube -- Chief Executive Officer

Yes, that's absolutely right.

Liisa Bayko -- JMP Securities -- Analyst

OK. For CTX, can you talk about sort of the -- a little more specifically about the growth opportunity in doing the study? Maybe you can quantitate it in some way in terms of maybe additional number of patients that you could maybe able to treat or some percentage growth that you might expect or something along those lines. Just give us a sense of what we're talking about.

Eric Dube -- Chief Executive Officer

Sure. Thanks, Liisa. So just as a reminder, the rationale for doing the study was to make sure that we have a label for this treatment that has been around for some time and is considered a very important treatment option for these patients. I'll ask Peter to talk a little bit about what he sees as the opportunity if and when we receive the approval.

Peter Heerma -- Chief Commercial Officer

Thanks, Eric, and thanks, Liisa, for the question. Based upon what we know today and the fact that CTX is an ultra-rare population, with Chenodal currently available as the standard of care, we do not anticipate a material change in the market opportunity. We would, however, like to pursue additional investments in raising awareness and ultimately, earlier diagnosis to help patients. We think it's appropriate to give the right guidance for our field force to the physicians, so they are in a good position to write a prescription for Chenodal.

Liisa Bayko -- JMP Securities -- Analyst

OK. I thought part of it was to maybe uncover to be able to kind of look for more patients. But I guess is that sort of an unknown? OK, OK...

Eric Dube -- Chief Executive Officer

Yes, I think it's certainly -- yes, Liisa, thank you. Certainly, it would give us the opportunity. As we've done over the last few years with our promoted products, finding these rare and ultra-rare patients is not an easy task, and so with something like CTX, where we don't promote it, we think that we'd be able to help in identifying these patients. I'd say right now, we're not in a position to say that it's going to have an inflection on any of the growth that we've seen with that product.

But I think it's going to be, as Peter says, an opportunity for us to continue to raise awareness, and hopefully, for these patients to be able to get that diagnosis and connected to treatment even earlier. And once we get closer to completion of that trial and filing, we could talk more in detail about what that might look like.

Liisa Bayko -- JMP Securities -- Analyst

OK, great. Thank you.

Operator

Your next question is from the line of Tim Lugo with William Blair. Please go ahead.

Lachlan Hanbury-Brown -- William Blair -- Analyst

This is Lachlan Hanbury-Brown. Thanks for taking the questions. You sounded pretty positive on the PROTECT enrollment. So I was just wondering what -- and you mentioned that leveraging your footprint and increasing awareness has helped with the enrollment there.

Are there any other specific learnings you've been able to apply from DUPLEX that have helped there? And are there any more that you're sort of in the process of implementing that could further speed up the rate of enrollment?

Eric Dube -- Chief Executive Officer

Thanks, Lachlan. Noah, why don't you take this one?

Noah Rosenberg -- Chief Medical Officer

Yes. Number one, I would say, to reemphasize the foundational sites, I think that's a key point. We continue to grow the site footprint. And I think it's really important that you have a global reach.

I would also say that one thing that we've observed, and I think this maybe why PROTECT is benefiting. Beyond the fact that PROTECT is a little bit of a larger population or IgAN is a larger population, when you recruit these studies, we have a pretty big overlap between the two studies. So PROTECT and DUPLEX, we have a substantial overlap there. And physicians as investigators, what they'll typically do is they will enroll a patient and they'll see how that patient does on therapy.

In their hands, they want to make sure that patient does well. They're comfortable, they're confident. Once they do that, then sometimes you'll actually see them enroll two or three, they'll start to bring in more patients. They want to make sure they're confident and comfortable.

And I expect what's happened is for sites that are bringing in DUPLEX patients, they're getting comfortable and confident with sparsentan, and now they're bringing in patients onto the PROTECT side. So I think it's kind of a hand-in-hand thing. It goes back to the well-understood mechanism, they understand how the drug works, they're comfortable with it. So I think that's a big part of it.

We continue to drive a number of strategic imperatives. I'll just add one that's going to be -- that is key and important. It's been helpful. And community key is we talked in the last call about the 9,000 nephrologists in United States, 300 academic sites and 8,700 sites that are community-based nephrologists, and we continue to extend the connectivity between the academic sites and the community-based sites.

And here I'm specifically speaking about the U.S., which has got a pretty substantial amount of enrollment in DUPLEX and in PROTECT as well. Those are the kinds of things that we're doing. We will continue to drive those efforts to bridge and broaden out that enrollment and accelerate recruitment.

Lachlan Hanbury-Brown -- William Blair -- Analyst

OK, great. And can you give a sense of -- in terms of the recent uptick, is that mostly coming from those centers that already have patients enrolled? Or is that primarily driven by the addition of new centers?

Noah Rosenberg -- Chief Medical Officer

Yes. I would say it's a combination. We'll see sites as far as more recruiting and continue to recruit. But it's interesting, in this disease, we'll also see sites that haven't recruited in six months, bring a patient in.

So it really depends on the site. Yes. And the other thing is, I mean, just remember, PROTECT is moving very well. Trends continue, and we're pretty encouraged we could reach our enrollment milestones early, potentially.

And I think I just want to -- I'll leave it there.

Lachlan Hanbury-Brown -- William Blair -- Analyst

Thank you.

Operator

And your final question comes from the line of Lina Kaminski with Canaccord. Please go ahead.

Lina Kaminski -- Canaccord Genuity -- Analyst

Hi, guys. Thank you. So it's Lina for Michelle. So one of the things that were mentioned at ASN for the SONAR study was the higher baseline UACR in non-responders versus responders.

So given the majority of FSGS patients, they have higher proteinuria, do you think this would be true to FSGS around the population that is most likely to respond? And I guess have you done any analysis on this with respect to DUET population?

Noah Rosenberg -- Chief Medical Officer

Yeah. I mean, I believe there is an analysis. There's a whisker plot in the DUET paper that, Lina, I think it's a great question that speaks roughly to this. Chris can provide it after the call.

But yes, we've looked at the cut point of above and below. It was two or three was the cutoff there for -- in this case, UPC, or we're using UPC in this case. But yes, we've looked at that, and there appears to be an effect both above and below that "nephrotic-range proteinuria level" that you're getting at.

Lina Kaminski -- Canaccord Genuity -- Analyst

Got it. And then just another one on Alport syndrome. Since you mentioned that earlier on the call, just wondering, it seems like you're still looking at this. Can you maybe provide some color on kind of how the competitive landscape influences your decision on making the progress on this disease, specifically since bardoxolone has a risk of fluid retention? And this may prevent ability to dose it in combination with sparsentan.

Noah Rosenberg -- Chief Medical Officer

Yes, Lina, thanks for that question. We are looking at that. And certainly, we want to make sure that we understand how the market and the treatment paradigm may evolve. But also part of our assessment is looking at what the clinical and regulatory path would look like.

We will continue to look at how other products may be developed and used, and we think that there potentially could be a role for sparsentan. We're not in a position really to talk much in more detail about that or about the potential competitors in that space, but I will say that we will go into that if we believe that there is a clear role and a clear pathway for sparsentan.

Lina Kaminski -- Canaccord Genuity -- Analyst

Thank you. This is super helpful, and congrats again on the quarter. Thank you.

Eric Dube -- Chief Executive Officer

Thanks, Lina.

Operator

And I'm showing no further questions at this time. I would now like to turn the conference back to Chris Cline for closing remarks.

Chris Cline -- Vice President, Investor Relations and Corporate Communications

Great. Thank you, Angela, and thank you all for joining us today. This concludes our call. We look forward to seeing you over the next few weeks at the upcoming investor conferences.

Operator

[Operator signoff]

Duration: 58 minutes

Call participants:

Chris Cline -- Vice President, Investor Relations and Corporate Communications

Eric Dube -- Chief Executive Officer

Noah Rosenberg -- Chief Medical Officer

Laura Clague -- Chief Financial Officer

Joseph Schwartz -- SVB Leerink Partners -- Analyst

Maury Raycroft -- Jefferies -- Analyst

Bill Rote -- Senior Vice President of Research and Development

David Hoang -- Barclays Capital -- Analyst

Jackson Harvey -- Nomura Instinet -- Analyst

Liisa Bayko -- JMP Securities -- Analyst

Peter Heerma -- Chief Commercial Officer

Lachlan Hanbury-Brown -- William Blair -- Analyst

Lina Kaminski -- Canaccord Genuity -- Analyst

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