Good morning, and welcome to Mirum Pharmaceuticals' business update call. My name is Ben. I will be your operator today. All lines are currently in a listen-only mode. There will be an opportunity for Q&A after management's prepared remarks. I would now like to hand the conference over to Andrew McKibben, SVP of Strategic Finance and Investor Relations. Please go ahead.
Thank you, Ben, and good morning, everyone. I'm very happy to welcome you to Mirum's conference call to discuss our recent clinical readouts, including the top-line results of our VISTAS phase II-B study of volixibat in patients with primary sclerosing cholangitis, or PSC, and last week's announcement of top-line results from the phase II portion of the AZURE-1 study of brelovitug in hepatitis delta. For our prepared remarks, I'm joined today by our CEO, Chris Peetz, and our Chief Medical Officer, Joanne Quan. I'm also joined by our President and Chief Operating Officer, Peter Radovich, and our Chief Financial Officer, Eric Bjerkholt, who will both be available for Q&A. The call will begin with opening remarks from Chris, followed by Joanne, who will review the clinical data. After prepared remarks, we will open the call for Q&A.
Earlier today, Mirum issued a press release announcing the VISTAS Phase II-B study results. A copy of that release, along with a presentation summarizing these results, is available on the Investors section of our website. Before we start, I'd like to remind you that during the course of this conference call, we will be making certain forward-looking statements based on management's current expectations, including statements regarding Mirum's programs and market opportunities for its approved medicines and product candidates, and financial guidance. Inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. We are under no duty to update these statements. Please refer to the risk factors in our latest Form 10-K and subsequent SEC filings for more information about these risks and uncertainties.
With that, I'd like to turn the call over to Chris. Chris?
Thank you, Andrew McKibben, and thanks to everyone joining our call today. It has been a busy couple of weeks for the Mirum clinical team. Today marks a defining moment for Mirum and, more importantly, for patients living with PSC. We are very pleased to announce that the VISTAS study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in cholestatic pruritus for PSC patients treated with volixibat. These results represent the first successful demonstration of a therapy addressing a core symptom of PSC in a controlled study and positions volixibat as a potential first approved medicine for patients. PSC is a progressive and highly burdensome condition with no approved therapies. For patients, pruritus is not a secondary concern. Along with fatigue, it is often one of the most debilitating aspects of the disease, impacting sleep, daily function, and overall quality of life.
These results highlight the potential for volixibat to meaningfully change the treatment paradigm in PSC. It is a transformational moment for Mirum as a company, as this progress comes on the heels of the Phase II-B portion of the AZUR-1 study of brelovitug in hepatitis delta we shared last week. Our commercial team looks forward to the potential to bring both of these standard of care-changing medicines to patients. Before turning it over to Joanne to walk through the highlights of the VISTAS data, I want to also acknowledge the patients, investigators, and advocacy groups who made this study possible. PSC is a challenging disease to study, and their commitment is reflected in the strength of these results. Now over to Joanne. Joanne?
Thank you, Chris. I'm very pleased to review the results from the VISTAS study, and I will also take a few minutes to walk through the top-line results of the AZUR-1 phase II-B study we announced last week. First, I would like to extend my gratitude to the patients, investigators, and study teams whose participation made this work possible. PSC is a chronic progressive cholestatic liver disease characterized by impaired bile flow, leading to the accumulation of bile acids and subsequent liver injury. Patients experience fluctuating elevations in liver enzymes and progressive fibrosis, often accompanied by the development of biliary strictures and recurrent and unpredictable episodes of acute cholangitis that can require repeated endoscopic or interventional procedures to manage. PSC can ultimately result in cirrhosis, liver failure, and the need for liver transplantation. PSC is also associated with extremely increased risk of cholangiocarcinoma.
Importantly, beyond disease progression, patients carry a substantial symptomatic burden, particularly cholestatic pruritus and fatigue, which meaningfully impacts daily functioning and quality of life. As a reminder, VISTAS is a phase II-B randomized, double-blind, placebo-controlled study evaluating volixibat in patients with PSC and pruritus over 28 weeks. Patients with moderate to severe pruritus at baseline were placed in the primary cohort, and patients with mild pruritus at baseline were evaluated in the secondary cohort. All patients were included in the safety evaluation. All patients were randomized to receive volixibat 20 milligrams twice daily or placebo. Baseline demographics and patient characteristics were well-balanced across study arms in the primary cohort, with a mean baseline itch score of about 6 out of 10, reflecting the severity of itch in this patient population.
Consistent with PSC, slightly over 70% of patients had concurrent inflammatory bowel disease, and baseline liver function tests were characteristically elevated and generally comparable across study arms. The primary endpoint evaluated the mean change from baseline in pruritus compared to the average of the last 12 weeks of treatment using a mixed effects model with repeated measures analysis. Pruritus was assessed using the Adult Itch Reported Outcome, a once-daily 0-10 numerical rating scale, with a score of 10 being the worst itch. I'm very pleased to say that volixibat demonstrated robust and statistically significant reductions in itch. Specifically, treatment with volixibat saw a 2.7-point reduction in the itch score compared to a 1-point reduction for patients receiving placebo. This translates to a placebo-adjusted improvement of 1.64 points with a P value of less than .0001.
We believe this is an outstanding treatment effect, the magnitude of improvement is consistent with what we have observed in other cholestatic indications and reflects a meaningful benefit for patients. The safety profile of volixibat was consistent with the known effects of IBAT inhibition, characterized by gastrointestinal adverse events and changes in liver laboratory parameters such as alanine aminotransferase, ALT, and total bilirubin. There were similar numbers of patients in both treatment groups with grade 3 or higher treatment emergent adverse events, there were no treatment-related serious adverse events. There were eight patients in the volixibat group and five in the placebo who experienced serious adverse events. In general, these were reflective of the course of their underlying disease. There were seven patients with treatment emergent adverse events leading to premature study discontinuation in the volixibat group and two in the placebo group.
Of the seven patients in the volixibat group who discontinued the study, three were for diarrhea. 40% of patients on volixibat had treatment emergent diarrhea compared to about 9% on placebo. Elevations in ALT, AST, ALP, and bilirubin were observed more frequently in volixibat-treated patients than placebo-treated patients. This trial represents an important step toward bringing a potential first-in-disease treatment option to patients with PSC. We are looking forward to presenting the full results as an oral late-breaking presentation at the EASL International Liver Congress at the end of May. We also plan to review these results with the FDA at a pre-NDA meeting scheduled for this summer. Following this interaction, we plan to submit an NDA in the second half of this year. A quick reminder on the recently announced Phase II-B portion of the AZURE-1 study, which also met its primary endpoint.
AZURE-1 is evaluating treatment-naive hepatitis delta patients randomized to 300 milligrams once weekly, 900 milligrams once every four weeks, or delayed treatment, with a 24-week primary composite endpoint of virologic response and ALT normalization. This is an earlier time point than the 48-week phase II brelovitug data previously shared at AASLD. In the first 53 patients evaluated at week 24, brelovitug demonstrated robust antiviral activity across both those groups, with 100% of patients in the 300 milligram arm and 75% in the 900 milligram arm achieving virologic response, compared to 0 in the delayed treatment arm. The primary composite endpoint was achieved in 45% and 35% of patients in the 300 milligram and 900 milligram arms, respectively, versus 0 in the delayed treatment arm.
Importantly, we continue to see further reductions in ALT and hepatitis delta RNA beyond the 24-week time point. brelovitug was well tolerated across those groups, with no treatment-related serious adverse events and very low rates of flu-like symptoms. Overall, these results reinforce a compelling profile for brelovitug as a potential well-tolerated, convenient, single-agent therapy for hepatitis delta and provide confidence as we look ahead to top-line data from the Phase III AZURE-1 and AZURE-4 studies in the second half of this year. We look forward to presenting full results from the Phase II-B portion in a late-breaking posted presentation at EASL. With that, I'll turn it back over to Chris.
Thank you, Joanne. These results represent a major milestone for Mirum, advancing potential game-changing new medicines to patients. Stepping back, Mirum is entering a new phase of growth and value creation. We now have a high-performing commercial business that continues to generate strong and durable growth alongside two emerging therapies in adult liver disease, each with important upcoming milestones as we move towards potential registration. Looking ahead, our focus is clear. For brelovitug and hepatitis delta, we are on track with the AZURE-1 and AZURE-4 phase III studies, with top-line data expected in the second half of 2026. For volixibat and PSC, our next step is this summer's pre-NDA meeting with the FDA as we prepare for potential NDA submission in the second half of the year.
In parallel, we will continue to advance the VANTAGE study in PBC through its confirmatory stage, with top-line data now expected in the first quarter of next year. For the balance of the pipeline, the LIVMARLI EXPAND study is on track for top-line data in Q4, and we expect top-line data from MRM-3379 in Fragile X syndrome next year. Taken together, we see a clear opportunity to extend our leadership in rare disease, building on the same foundation that has driven our success to date. Once again, thank you to the patients and investigators who participated in VISTAS and AZURE-1, and a huge thank you to the Mirum team who are working tirelessly to make these major advances in research possible. With that, operator, please open the line for questions.
We will now begin the question and answer session. Your line will remain open for follow-ups. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question comes from the line of Ryan Deschner with Raymond James. Ryan, your line is open. Please go ahead.
Hi, good morning, and thanks for the call. Congrats on the data set. What did you learn from the baseline characteristics of the enrolled population and the placebo response in this study with regards to patient heterogeneity and how chronic or intermittent pruritus can be in the PSC indication? I have a follow-up. Thanks
Thanks for the question, Ryan. Yeah, I mean, a first observation on that, I mean, we've enrolled this study for pruritus, that shows up in the baseline criteria. You know, one of the things that I think worked very well in the study design and give credit to the team here at Mirum, is you see a quite low placebo response on those pruritus values. Not only does that point to good study conduct, but also shows that, you know, the concept that has been talked about of intermittent pruritus and PSC is not really something that showed up in these patients.
This, that placebo arm, you see persistent itch throughout the study, which is, you know, I think kind of a new finding for a study like this, being the first time we've looked at pruritus in this amount of detail in PSC. What was your follow-up?
Quick question on the pruritus signal seen in the mild pruritus patients, statistically significant, which is impressive to see. Can you remind us what range is considered mild, and if you can, the mean baseline ItchRO score for this mild group? Thanks.
Yeah. We're not discussing the specifics of that at this point. Just to kind of reassure you that, you know, we did measure it carefully, and then sorted the patients kind of based on their severity of their itch at that point. You know, essentially, based on the 0 to 10 ItchRO scale, there's kind of less room to move when you look at the mild pruritus. I think that actually makes the results, you know, pretty satisfying for us in that group as well. We certainly didn't expect to see that statistically significant response, but I think that just shows you know, how well the look of that works.
Yeah. We'll look to have some of that data presented at one of the upcoming conferences. The baseline was really just over 2. It was about 2.3. To have a significant move from that baseline was a great finding from the result.
Excellent. Thanks and congrats on the data.
Thanks for the questions.
Your next question comes from the line of Josh Schimmer with Cantor Fitzgerald. Josh, your line is open. Please go ahead.
Great. Thanks for taking the question, and congrats on another positive trial. Did you get a look at the interim analysis of the VISTAS study and how that compared to the final results, since there may be some relevant read-throughs to how we interpret the interim from the VANTAGE trial? Maybe you can talk a little bit about why the magnitude of separation in PSC may not be quite as large as you've seen in PBC. Thank you.
Thanks for the questions. Yeah, we did, as part of the unblinding, we did see the results from the interim portion. Overall, consistent profile. What I'd say is, you know, the way we designed this study, having the data monitoring committee make the dose decision, in viewing the results, you know, all generally consistent with the final results, I think we would have made the same decision if we had been unblinded. Overall, again, you know, pleased with how the study design and conduct played out here. In terms of the magnitude of change, you know, we powered this study on a 1.75 change versus placebo, really saw that coming, very much in line with that.
What played out differently from a statistical standpoint was the variability of the data was much lower, so a much tighter response range. Placebo performance that we talked about before, that ended up with a, you know, higher significance from a statistical standpoint.
In terms of the underlying disease biology, any reason why one would be more responsive than the other?
Josh, you know, I think that's a good question. You know, I think we have to remember that PSC and PBC are really different diseases. I know, you know, we're doing studies of volixibat in both of them. We consider them under the umbrella of cholestatic pruritus. If you think about just the course of disease and the origins, they're quite distinct. With PSC really showing, you know, a lot of fluctuation, both biochemically as well as just in the clinical course. You know, patients with cholangitis that can occur. Some patients have multiple episodes. They may have biliary strictures require intervention. That fluctuating disease course with kind of underlying progression is a bit different than kind of the slower kind of monotonic progression that you see in PBC.
I think we see that as well in terms of labs and also just, you know, the, you know, how these patients behave during the course of six months. I think, you know, even though we have kind of lined them up side by side and we're studying the volixibat in two different studies, they are different disease entities. I think it is difficult to claim in different disease condition. To our view, I mean, this is really the only controlled study of itch in PSC that's out there, and I think the result is a robust and it's one.
Got it. Thanks very much.
Thanks for the question.
Your next question comes from the line of Swayampakula Ramakanth from H.C. Wainwright & Co. Your line is open. Please go ahead.
Thank you. Thanks for doing this call, Chris and team. two quick questions from me. The first question was on the hepatic safety. Can you quantify the magnitude and reversibility of the ALT, AST, and bilirubin elevations? Were there any Hy's Law cases? In terms of the discontinuations of 9.1%, you know, can you help us understand what percent was LFT driven versus diarrhea driven? The second question is on the breadth of the label. Obviously, the mild itch secondary cohort showed statistical significance, which is pretty good. Do you think you can get a label which covers all the way from mild to severe populations?
Yeah. Thanks for the questions. I'll start with the label and then have Joanne comment on some of the safety profile questions. You know, overall, the labeling we've seen for IBATs as a class really just points towards pruritus being the indication, cholestatic pruritus. There's not really a concept of grading of severity. That's kind of what we expect to play out here. I'd also say, you know, kind of on the labeling, this kind of reads into the safety profile here for what we see in this study. The results are pretty consistent across IBATs as well in terms of the liver safety and having monitoring labeling as part of the class. Expect that to be part of an eventual volixibat label as well.
I'll have Joanne speak to the specifics.
Thanks for the question. You asked about Hy's Law. I think, you know, you're aware that Hy's Law really was developed in the setting of having, you know, a normal liver, and obviously these patients don't have a normal liver. Actually we also know that PSC disease without volixibat or any other treatment by itself actually can be associated with fluctuations in some of the biochemical abnormalities that look dyslike Billy. All of those things make it pretty difficult to kind of sort out all this. We're in the process of, you know, putting that together. We'll be reviewing it with some independent, external folks to help us with that assessment.
You know, for today, I think, you know, Wiggy, what's important to note is just so you can see on the adverse event slide, I think, which is in slide 10 of the deck, you can see, you know, some of those things reflected the underlying changes, you know, essentially in some of the, what we viewed as clinically significant lab elevations like ALT, bilirubin.
Specific to your question on discontinuation, there was one patient who discontinued for lab elevations in the volixibat arm.
Yeah.
Okay. Okay. Thanks. Thanks for taking my questions.
Thanks for the questions.
Your next question comes from the line of Gavin Clark-Gartner with Evercore ISI. Your line is open. Please go ahead.
Hi, this is Yesha on for Gavin. Thanks for taking the question. I was just wondering if you guys could speak to what you saw in the patient-reported outcomes, specifically around fatigue and sleep. Were you able to note directional improvements or nominal significance across any of the groups?
Hi, Yesha. Thanks for the question. We did see trends in fatigue and sleep in terms of improvements that favored volixibat. For fatigue, you know, it was a trend and because of the way that we set up the hierarchical analysis, once we start missing something, then we're kinda technically not allowed to go further, because the FDA kinda holds our feet to the fire for that. The nominal P value for sleep was actually significant, however. I think this actually all kinda hangs together. It makes sense. You know, we significantly improved itch, trend in fatigue, trend in sleep.
You know, the fatigue and sleep were included in the study to kind of give us some insight into that, but, you know, obviously, the study itself is not designed to look for those improvements. I think the overall data really kind of hangs together for what we would expect.
Awesome. Thank you so much.
Thanks. Thanks for the question.
Your next question comes from the line of Mani Foroohar with Leerink Partners. Your line is open. Please go ahead.
Hey, guys. You have Ryan on from Mani. Thanks for taking our question, and congrats on the data. How should we think about the differences in baseline characteristics, whether that be gender or serum bile acids, and how that may have impacted the results between the two arms? Then maybe just one commercial one. Can you guys just talk about your launch expectations given, you know, this is moving into an adult setting. Based off our channel checks, pruritus is not active or proactively asked about by physicians. Maybe just some initial launch expectations as well as we look into next year. Thanks.
Hey, Ryan. Thanks for the question. Your question was about impact of gender differences and serum bile acid differences. You know, I'm not sure that that has a big impact really. You know, the gender balance was fairly equal among both sides, I think, in terms of the groups, 46% versus 61% being female. I don't think that's that big of a difference. You know, the study result is strong, I doubt that that has any impact on it in terms of that. In terms of the serum bile acids, you know, there is an imbalance at baseline, the serum bile acids in the volixibat group is higher. However, both of those values are significantly higher than normal.
Again, I think that reflects, you know, probably, you know, a few kind of outliers there. We don't really read a whole lot into that. You know, patients were not selected based on serum bile acids. They were selected based on itch. I think that's where, you know, where we look to the interpretation is that we selected patients with pruritus, and it demonstrated improvement in pruritus. I think that's where we, that's where our takeaway is. Obviously, we'll look more closely at bile acids and other predictions at some later point.
Ask Peter maybe to speak about the launch expectations.
Yeah. Thanks for the question, Ryan. I think, you know, it's an astute point. Certainly if, you know, if you do doc calls, you'll hear a wide range of
Clinical practices and estimates for pruritus and it's, you know, not as front and center today as it should be, perhaps, because there are no approved therapies and nothing to offer these patients. This will be our wood to chop as we move towards launch. It's not an unfamiliar exercise for Mirum. It's, you know, this is somewhat similar to what we had to do on the pediatric side over the last five years. And we'll, we will expand our team to have a larger footprint in adult care settings. Really excited about the opportunity to have the potential first approved therapy in this setting.
Thanks, guys. Congrats again.
Thanks for the question.
Your next question comes from the line of Joseph Thome with TD Cowen. Your line is open. Please go ahead.
Hi there. Good morning. Congrats on the data, and thank you for taking my questions. Maybe the first one, just a bit of bookkeeping. Can you comment, is this all you need from a safety database side of things for the NDA submission, or do you need to follow these patients for any longer, and that might be gating to the H2 submission in any way? Can you comment a little bit in the real world, how often are these patients assessed for liver enzymes when they're seen with their physicians? Maybe last quick question, how do you think about any necessary changes to your sales force once hopefully volixibat is approved and available to your team? Thank you.
Thanks for the questions, Joe. I'll start off, we'll pass it over to Joanne on monitoring and Peter on the commercial team. This overall and the expectations for the NDA submission, we do see this as everything we need from a clinical standpoint for the NDA. Given the size of PSC as an indication, this is a substantial safety database. Just as a reminder that this conversation and expectation with FDA is that this will be submitted for a full approval with pruritus being the outcome for the basis of that approval. Looking forward to discussing all that with FDA this summer. Then maybe Joanne can speak about kind of standard of care monitoring in PSC.
Yeah. You know, these patients, because of their risks and just their clinical course, are seen fairly frequently. I mean, you know, their risk of cholangiocarcinoma is actually quite high. I believe the AASLD recommendations are they're essentially monitored every six months or so. If they have cirrhosis, they're also monitored for hepatocellular carcinoma. As well, many of them have, you know, might have episodes of acute cholangitis, which bring them in as well, and they may need procedures for that. This is a fairly closely monitored population just because of the complication rate, you know, of their underlying disease.
In terms of our, you know, field force sizing, as mentioned before, we will be expanding. You know, just to use the U.S. as a frame of reference, I mean, today we have about 15 folks on the sales side doing, you know, the liver side of things, which gives us a strong presence across the board in pediatric care delivery settings, as well as, I would say, the top decile, the biggest centers on the adult side where we're finding adult PFIC patients. We'll expand into probably somewhere in the 60s total on the liver side. That'll actually, we'll use that team to promote brelovitug, if approved, in hepatitis delta.
That'll allow us to get into the full kind of setting where PSC patients are taken care of and also hopefully, you know, find more adult PFIC patients out there.
Great. Thank you very much.
Thanks for the questions.
Your next question comes from the line of Jessica Fye with JP Morgan. Your line is open. Please go ahead.
Hey, guys. Good morning. Thanks for taking my questions. I had a couple on volixibat and then one on brelovitug. On volixibat, do you expect that the 56% versus 26% 2-point responder secondary endpoint data could get on the label? Second, on volixibat, it's between the, I think it was north of a 2-point placebo-adjusted benefit you saw at the interim in pruritus with PBC and the 1.64-point delta you saw today in PSC. Can you talk about your confidence in being able to deliver data in pruritus with PBC that would compare well to linerixibat?
On brelovitug, with the 300 weekly and 900 Q4 week data looking directionally different from the prior data, acknowledging the different time points, is it your expectation right now that you'll likely file for both the 300 weekly and 900 monthly brelovitug dosing regimens? Thank you.
Thanks for the questions, Jess. Yeah, I'll touch on some of those. You know, first on the label and what we'll be proposing for volixibat. You know, again, the indication statement that we're proposing we expect to have is treatment of cholestatic pruritus and PSC. Then in the, you know, clinical trial description, there'll be some discussion of the FTC data. Ultimately, at this point, unclear whether that response rate is one of the specific data points that's in there. A little early to be able to speak to specifically what we think will end up in there.
You know, speaking on PBC confidence, you know, given what we saw in the VANTAGE interim, what we're seeing here, I think we're in really good shape heading into the full analysis for the VANTAGE study. This is what we're seeing now consistently with volixibat, really strong placebo-adjusted.
A difference here. In particular with the PSC results, the VISTAS results, just as a basically the ratio of placebo change to drug is really remarkable. I think that speaks quite a bit for the VANTAGE study as well in the first quarter next year. Kind of moving down to bulevirtide, maybe you can have Joanne comment a little bit on the findings. You know, ultimately in the phase III study, both doses are in there in the final analysis, and we'll be able to make that determination when we have the data in terms of the filing package. I'll let Joanne speak to kind of what we observed from those two dose levels.
Yeah. Jessica , thanks for the question. You know, you're correct that directionally they were a little bit different. I think, you know, we have to remind ourselves that the dataset is fairly small. You know, we are running the phase III studies for the phase III for AZURE-1 and as well AZURE-4, and we'll make a final determination at the end of the year when we unblind those. I think we're hesitating from making too big conclusions based on a limited dataset. Directionally, you know, we feel confident in the results. You know, we're sticking with that, and we think this is actually, you know, overall very consistent with the prior phase II data that we presented.
no major differences there.
Thanks.
Thanks for the questions.
Your next question comes from the line of Mike Hall with Morgan Stanley. Your line is open. Please go ahead.
Good morning. Thanks for taking the question, and congratulations on the data as well. Maybe just to follow up on the significant benefit you saw in the mild patients, which I think was a bit of a positive surprise for us. I guess, does that change your view on the potential market opportunity for brelovitug? Then I have a follow-up.
Yeah. Thanks, Mike. Yeah, I mean, it certainly is nice to have that data and, you know, our message with LIVMARLI has always been any level of pruritus, you know, is a, is a signal, and it deserves to be treated. To have that data in hand, I think, you know, will be, you know, kind of helpful for the launch effort. I don't know if it fundamentally transforms. I mean, these are scales used in clinical trials in the real world setting. You know, it's unusual for someone to, you know, rigorously measure itch the way it's done in clinical trials.
I think what we've seen with LIVMARLI is that, you know, those patients do come to therapy, and we'd expect a meaningful proportion to do the same here.
Got it. Just for the upcoming pre-NDA meeting scheduled for this summer, anything specific you're looking to get clarity on from the FDA, or what's gonna be the focus there for you guys?
I would see it as a pretty routine pre-submission meeting just to align on, you know, a format of analyses and datasets. In terms of, you know, what's in the package overall, and we've had good communication throughout the history of the PSC program and also as part of the post the PBC Breakthrough Therapy Designation conversation. We've been able to get good feedback and clarity along the way. You know, don't feel that there's really much to be debated, so to speak. It's really just the standard pre-submission meeting.
Great. Thank you, and congrats again.
Thanks for the questions.
Your next question comes from the line of James Condulis with Stifel. Your line is open. Please go ahead.
Hey, thanks for taking my question and congrats on the data. Just wondering, you know, what we can expect at EASL in May in terms of like, additional data. Is that where we may see things like, you know, fatigue and sleep? Then maybe one more sort of follow-up on the commercial side of things. Totally understand it's way too early to be any sort of, you know, get into specifics, but just curious if there are, you know, good analogs to look at here as it relates to things like price and the launch, you know, as we approach a potential launch here. Thanks so much.
Thanks. On EASL, you know, a little early to comment on what specifically will be presented. Excited that EASL recognizes the importance of this dataset and that we're having one of the headline late breaker oral presentations. We, you know, do plan to get deeper into some of the analyses in that presentation. Maybe I'll ask Peter to speak to the commercial analogs.
I think probably the best analog we can think of is right here at home at Mirum. LIVMARLI in Alagille syndrome, you know, well-diagnosed disease, perception amongst providers of a variable, you know, pruritus phenotype. You know, we're almost five years in, you know, from our first launch in the U.S. there, and we've talked about how we've reached about a 50% penetration. We continue to add patients every month, every quarter, and have kind of clear line of sight to that being kind of the continuous adoption dynamic for the lifecycle of the product. As best we know, that's probably a pretty reasonable way to think about how a launch adoption curve looks in PSC.
Thanks so much.
Thanks for the questions.
Your next question comes from the line of Jonathan Wolleben with Citizens. Your line is open. Please go ahead.
Hey, thanks for taking the question. Just a couple for me. When you guys talk about the commercial opportunity in your slides, you mentioned that median worst itch score is typically around eight, and baseline here is more around the 6 level. Wondering if you captured the patients you wanted to in this primary group or, if there's any difference in the population here than you would have expected?
Thanks for the question, Johnny. Overall, I mean, we see this, the VISTAS population as really representative of, you know, what PSC looks like out there, both in terms of the pruritus burden and what we see over time. You know, kind of what we spoke to with the persistent itch on the placebo arm. You know, the rough proportion on how people are scoring their itch between the moderate to severe and the milder patients. Then also just the underlying kind of complications that happen in PSC patients that we saw throughout the study, just that it's a really tough disease. I do think we have a very representative population in the VISTAS study.
Okay. The diarrhea, it actually was a little bit better than we would've expected based on the VANTAGE interim. I wonder if you talk a little bit about categorization, temporal pattern, if there was any difference in the IBD population as well. Thanks.
Thanks for the question. The diarrhea was all grade 1 or grade 2, no grade 3 diarrhea in the double blind portion. In terms of kind of onset, you know, onset median within the first couple weeks of starting therapy. Duration in terms of the median is about a couple weeks as well. In most patients, not prolonged. It, you know, we looked carefully to see if, you know, giving an IBAT with a known characterized adverse event of diarrhea could trigger exacerbations, and we don't see an evidence of that.
There was a pretty careful look, in patients with IBD if they developed diarrhea, so we collected, you know, fecal calprotectin to see if we could see evidence of increased inflammation, look carefully for Clostridioides difficile and all of those other kind of causes. Currently we don't have any evidence that giving an IBAT to these patients actually increased IBD exacerbation. I think that's actually very reassuring for us and also for patients as well.
Your next question.
Thanks for the question, John.
Your next question comes from the line of Lisa Walter with RBC. Your line is open. Please go ahead.
Good morning. Thanks for taking our question and congrats on the results today. Just two from me. Did the 80% of patients on UDCA background therapy have a greater improvement with volixibat added on versus those on monotherapy? During your pre-NDA meeting with the FDA, do you plan to discuss the potential for priority review for volixibat? Any color here would be helpful. Thanks so much.
Thanks for the questions, Lisa. Let's, you know, starting with the FDA conversation, we will propose priority review. I think this setting, you know, has tremendous unmet need and really fits the profile for priority review, so that'll be part of the conversation. Kind of on UDCA response, you know, initial look, we're not seeing really any difference in response across different criteria. Still early in cutting the data, but nothing really to speak to out of the top line results. Well, thanks for the questions.
There are no further questions at this time. I will now turn the call back to Chris Peetz for closing remarks.
Great. Well, thanks everybody for joining the call this morning. Really excited about bringing volixibat forward to for PSC patients, and we also look forward to providing our Q1 update later this week.
This concludes today's call. Thank you for attending. You may now disconnect.