Christopher Peetz: Thanks for the question, David. Yes, it’s a really interesting situation watching this unfold. And I think just for a little bit of background on this, the key factor is to maintain orphan designation is to have some significant benefit over available therapies. That’s our understanding of what the recent outcome was with EMA on the recent Alagille syndrome decision. And we’re waiting to hear back for final feedback from EMA. We’re optimistic about the data set that the March PFIC study provides in that it’s a broader genetic profile of patients. It starts at a younger age. It’s a stronger response rate. Those are all things that we included in our submissions and some of the briefing materials on this point. And we should have an update on feedback from the agency by the end of the year.
Operator: We now have Brian Skorney of Baird.
Brian Skorney: My question is also on EMBARK. Can you just give us a little bit of an idea of how you sort of characterize the primary, the change in bilirubin, what that means versus the secondary endpoint of getting patients below 2 mg per deciliter? And just in time, in terms of expectations for the placebo arm on that secondary endpoint, I think the ChiLDReN Liver Disease Research Network said that about 50% of infants post-Kasai at 3 months had bilirubin less than 2. So is that a reasonable assumption for the placebo rate or for that endpoint in EMBARK? Is there anything to consider in the design that might make that more or less?
Pamela Vig: Yes, thanks for the question. So maybe I’ll start with your last question first. So in the natural history, that shows that somewhere between 7.5 to 10 from the literature post-Kasai, and less than half of those patients will clear jaundice. So the majority of those patients will remain elevated to varying degrees. And as you alluded to, those patients that do really well and have good established blood flow, less than 2 milligrams per deciliter, they’ll do pretty well. But the majority of them are really between 2 and greater than 6. And so we’ll also be looking at if we shift patients from high risk, meaning greater than 6, to moderate risk between 2 and 6, and maybe those from moderate risk to low risk. So we’ll be looking at bilirubin in all different ways.
And our primary endpoint, to answer your first question, is looking at the proportion, the percent change difference between active and placebo at month 6 using an NMR analysis. And I think that was it. Was there another question?
Operator: We now have Ed Arce of H.C. Wainwright.
Ed Arce: This is Thomas Yip asking a couple of questions for Ed. So first, congratulations on the positive RESTORE data set earlier this month, earlier last month, actually. So can you talk about a little bit about CHENODAL, NDA filing, and CTX in the first half of next year? In addition to RESTORE data, what do you anticipate will be part of the data package? Would that be historical data or post-marketing usage data?
Christopher Peetz: Thomas, thanks for the question. Yes, the NDA approach we see as relatively straightforward here for CHENODAL. There’s been extensive back and forth with FDA on what they’re expecting for the NDA in the discussion of the RESTORE Phase III study design. So that was something that we did work on and got comfortable that there was good alignment with FDA, that this would support an NDA for the CTX indication. And the NDA will include kind of the typical battery of additional data analyses that you’d see for a small molecule application. So nothing particularly unique about the NDA overall.
Ed Arce: And then perhaps just one more question from us. For LIVMARLI and Alagille syndrome in the U.S. market as we get close to the end of the year, what’s your anticipated growth level for Alagille syndrome for 2024?
Eric Bjerkholt: We have not provided any guidance on 2024 at this point, and we’re still discussing internally whether we will and if so, what and when. So stay tuned on that.
Operator: We now have our final question on the line from John Wolleben of JMP Securities.
