The level of effort to create the quality of data needed in the database to address not only death in liver transplant but also liver-related events has really matured over the years. So we were able to collaborate with that group to develop an understanding of event rates incidence prevalence and to come up with a design that allowed us to estimate as you allude to the power of what we would expect to see in a patient population based on not only their natural history and rate of events. But also taking into consideration some thoughts around what we expect to be the risk reduction that we have seen in prior studies with CymaBay based upon the surrogate. So you know the surrogates have effects on the composite for example and we could factor that in.
So we think that we’ve — I guess, we could use the phrase thread the needle a balance between the practical aspects of asking patients to participate in a longer-term placebo-controlled study but for which they might have benefited. In this particular advanced population they’re really in many cases don’t have other treatment options especially Child-Pugh B. There’s nothing on label. Child-Pugh A there’s a limitation and agents that are approved that might be used in that population are not available in every country in every situation. So I think it’s a nice balance to really try to take into account the developing a scientific evidence placebo-controlled is the gold standard but also keeping the patient in mind. Having an opportunity it’s a 2:1 ratio active to placebo.
There’s an opportunity to get a benefit. They really in many cases have no other way to go. And then — and it’s a fixed duration. It’s not a — some of these event-driven trials typically would enroll a patient they go on placebo and they just go and tell you collect a total number of events which could be many, many years many more than three years in duration.
Steven Seedhouse: Thank you so much.
Sujal Shah: And Steven just to end it out, I know you asked about cirrhotics and non-cirrhotics. We do believe that regulators have at least confirmed that chilling outcome in the cirrhotic population will pertain to the broader population.
Operator: Our next question comes from Kristen Kluska with Cantor. Please go ahead.
Kristen Kluska : Hi everyone. Given the unique observations that you’ve shown with itch, are you planning to do more work around IL-31 in the RESPONSE study? And if so, when can we see that data? And then second, now that you have a larger N and number of patients you could follow, are there any other analysis you’re trying to conduct to further understand what’s driving your differentiated benefits? Thank you.
Sujal Shah: Yeah. I appreciate the questions, Kristen. Perhaps I can talk — I can ask Chuck to talk a little bit more about itch and IL-31 and I can answer the second question with respect to additional data sets coming out of ASSURE.
Chuck McWherter: Yeah. Thank you for that question, Kristen. Of course, we’re quite interested in delving into understanding the improvements in symptoms in particular itch that we’ve seen. And I think you’re probably alluding to a poster that we had in Vienna at the EASL meeting which correlated baseline itch with bile acid levels and IL-31 levels where we saw the PBC patients have up to 30-fold higher levels of IL-31 and known proteinogenic molecule at least in dermatological diseases. And we do of course have an interest and you can expect us to follow up on understanding that mechanism including in response. And as always our commitment will be to share it at a medical meeting as well as in publications. And we’re really trying to understand at the molecular and cellular level meaning which cells in the liver or elsewhere.
What’s the driver of IL-31 and can we develop convincing evidence that has — that we’ve seen so — to confirm what we’ve seen so far as to why seladelpar might be impacting itch in terms of a molecular explanation. So, stay tuned. You can be assured that we have a continued interest in this area.
Sujal Shah: And then Kristen you asked some great — sorry I just going to say you asked some great questions about number of patients today that are taking seladelpar north of 300 in ASSURE. Of course we’re also enrolling patients in the IDEAL study. And I’ll just very quickly tell you that our commitment to PBC patients of course doesn’t end with response or this Phase 3 data set or even our post-marketing commitment in AFFIRM. It is absolutely our intention to continue to generate data that helps us better understand the advantage of treating patients earlier, treating patients to normal, and better understanding the impacts on symptoms and how they translate to quality of life. And so both IDEAL and ASSURE we expect to be very rich data sets to serve for news flow and milestone generation for years to come.
Even as we hope to be successful at gaining approval for and launching seladelpar we’ll continue to generate data sets that support the potential for this to be a very differentiated option and a meaningful option for patients.
Kristen Kluska: Thanks. Looking forward–
Sujal Shah: Thank you.
Operator: Our next question comes from Cory Jubinville with LifeSci Capital. Please go ahead.
Cory Jubinville: Thanks for taking our questions. A couple from us. We touched upon this a little bit earlier in regard to the availability of existing therapies. But in AFFIRM how do you plan on tackling some of the feasibility challenges that might emerge, specifically keeping placebo patients on study assuming seladelpar may likely be approved within that timeframe?
Sujal Shah: That’s a great question. Maybe I’ll make a few comments and then invite Chuck to share anything in addition. Clearly there’s no question that long-term outcome studies as we mentioned are challenging in this setting. I think part of what’s unique around AFFIRM is a target to have a three-year fixed duration study. That’s really fed by assumptions with respect to event rates in compensated cirrhotic again specifically Child Pugh A and Child Pugh B. We hope that that will be one factor Cory ultimately that drives to greater feasibility in getting patients to participate. Chuck mentioned the 2:1 randomization so more likelihood of patients being on treatment. Of course you asked specifically about placebo. Of course this is a challenge.
