Peter Radovich: Sure, happily. I think with LIVMARLI, the short answer is that it’s largely stable. I think some of the puts and takes around that as we do geographic expansion with the first indication Alagille, we’ve already built a lot of that team and invested in a lot of the commercial activities. There may be some kind of minor incremental things, but nothing big enough with the geographic expansion to change things. As we expand to PFIC, that we’re going to take on the same geographies we’re in now, and it’s the same call universe. Again, maybe some very modest things is not enough to kind of show up on an overall SG&A number in a meaningful way that we would do to support that launch. And biliary atresia also taken care of in the same physicians and children’s hospitals that PFIC and Alagille.
So really LIVMARLI pretty stable. As we move to volixibat, that gets us into the adult setting, so obviously, we’ll have to have a team that can reach adult GIs and hepatologists. But we’ll look to leverage the team we have now and build from that as we get to those milestones.
Operator: The next question is from the line of Steve Seedhouse with Raymond James.
Ryan Deschner: Hi. This is Ryan Deschner on for Steve Seedhouse. Curious, in biliary atresia, what the timelines you anticipate for completion of enrollment in EMBARK. And then also, how will dosing in the EMBARK Phase to be handled? Will there be any sort of titration or starting dose?
Chris Peetz: Ryan, thanks for the question. I’ll pass it over to Pam to give a little color on the EMBARK study.
Pamela Vig: Yes. Thanks for the question. So we’re just super excited about the EMBARK study even if this would be the first study to read out in the IBAT inhibitor by the end of this year. So that speaks to the timing of when we expect the study to read out and complete enrollment. With regard to your dosing question, the dose that we’re using in this study is the same as our PFIC dosing, which is 600-microgram per kilogram twice a day. And what we saw in the PFIC study was really remarkable with regard to the reduction. That were really unexpected. And so that gives us a lot of encouragement, but we are hoping to see in this cellular study. The dose is titrated, as it is with our other studies, but the step-up start to and early on in the study thing throughout the remainder of the 6 months.
Ryan Deschner: Got it. That’s very helpful. And maybe if I could squeeze one more quick one in. Do you expect the bigger seasonality effect as it did in 2022 to come in 3Q, while the other quarters, I guess, going into 2020 remain fairly comparable?
Chris Peetz: We saw last year. It’s kind of hard to tell us that is going to be a recurring phenomenon. The summer travel season was a little more of the same post-COVID last year. I think it’s the simple way to put it. So a pretty good chance that we see some kind of effect like that where there are just fewer visits to start new patients. But important to note that throughout our third quarter last year and what we expect this year is as refills and the persistence to continue to be a real highlight for families on drug that they stay on drug. It’s a real highlight of the performance.
Operator: The next question is from the line of David Lebowitz with Citi. Your line is now open.
David Lebowitz: Considering that LIVMARLI is going to be in a competitive dynamic by the end of this year in two different markets, both LGS and PFIC. How do you see that affecting your commercial approach? Is there any risk of any competition on pricing in the market?
Chris Peetz: Thanks for the question, David. I’ll make a couple of comments. I mean the one thing that’s on pricing, that’s not something that we would expect to see. And particularly given some of the nuances of the position that we see in the market. And that LIVMARLI is really well positioned with such a great lead in terms of prescriber experience nearly 600 Alagille syndrome kids treated with LIVMARLI over the history of the program. That’s a tremendous amount of experience and most of that being overwhelmingly positive. So find ourselves in a position where I think we expect to see more of what we’ve seen in the launch to date, which is continued new patient starts and strong persistence compliance for patients that are on drug. And with the PFIC indication coming on really a step up in terms of what you’d expect to see for efficacy from the clinical profile. That’s going to be really powerful, excited for when our team can go out and talk about that data.
Operator: The next question is from the line of Brian Skorney with Baird. Your line is now open.
Brian Skorney: On the EMBARK study, I was hoping you could kind of talk through the relative importance as you see immune reduction in serum bile acid versus the proportion of patients with total bilirubin below 2mg/dL? And maybe even in context there, what the average baseline bilirubin we’re seeing in EMBARK, as well as what the lower threshold is that you’re allowing and also another size, why isn’t a 6mg/dL cutoff also being included as prospectively defined endpoint given the Schneider paper?
Pamela Vig: Yes. Thank you for the question. So basically, in biliary atresia, these kids, most patients continue to experience liver injury from accumulation of bile acids, right? And by reducing bile acid retention, you should improve BioFlo and bilirubin is an indicator of how well that bile is flowing. So you’re looking at both of these as markers. Early on after the size, when you can reduce bilirubin, that has been shown, as you’re mentioning in the Schneider paper that if you are 2 or less, you have a really good chance of maintaining relative liver if you’re between 2 and 6 it’s kind of mid-range. And if you’re greater than 6, you really are headed towards transplant. And that’s because the liver is, in fact, not functioning.
So bilirubin the most predictive marker of transplant, is an indicator of bile flow in liver injury. And I think that, as I mentioned, the data that we’ve seen from our PFIC study as a result of reducing bile acid retention in that setting and thereby reducing bilirubin is really encouraging for us on what we’re hoping to see in the BA program under retail.
Brian Skorney: And just any comment on what the baseline in EMBARK would be from a bilirubin perspective?
Pamela Vig: There is no threshold. All of these kids are coming in. They’re all pretty sick. They’ve had a procedure. They’ve got information. They’ve got the accumulation of bile acids and they have validated bilirubin.
Operator: The next question is from the line of Ed Arce with H.C. Wainwright. Your line is now open.
Ed Arce: A few for me. First, you mentioned earlier there were — or have been since launch, about 20% of patients diagnosed and addressable have received LIVMARLI. I just wondered if you could discuss the difference between that and actual market share now, given there’s some that, I would imagine some small numbers have cycled on or off. Is that pretty close to market share, and if not, what are the differences there? And secondly, wondering about PFIC when you would expect to get the NDA acceptance letter and PDUFA date there? And then, lastly, just thinking about the cadence of the three readouts later this year, two in the second half and one in the middle of the year. Just wondering if you could perhaps delineate a little more precisely what kind of gaps in between those we could expect or if maybe a couple are expected pretty close. Thanks so much.
Chris Peetz: Thanks, Ed, for the question. The first one kind of take through this year. On the first one, looking at market share, we continue to — for the U.S. business, to really just highlight that these are real dispenses in that revenue number. So you can look at those numbers as very direct patient volume being to expense real demand. So you can get a sense of that number just by looking at the U.S. net revenue number. In terms of some of the kind of milestone timing items, PDUFA data sign is typically about 2 months after submission. So we expect that to be in the next month or so based on when we submitted the PFIC sNDA and then on the other kind of clinical end points or clinical readouts, don’t really have any further color to get more precise than kind of midyear in the two in the second half.
Operator: The final question is from the line of Yasmeen Rahimi with Piper Sandler. Your line is now open.
Yasmeen Rahimi: Before I start my questions, just wanted to say thank you, Ian, and we will greatly miss you. Maybe the time of your last call, you’re going to be hosting with that. So wish you the best of luck and thank you again for everything, definitely under how…
