Joseph Hulihan: No, I’d just reiterate, the recent enrollment has come from newer sites, sites that have gotten up and running more recently. So, again, as Scott mentioned, screening is high, enthusiasm is high, and some patients just end up getting screened out. I think if we — I’m very encouraged by the continued screening efforts, and if we keep doing that, we’ll enroll the study. As in any study, there’s variability in how sites perform, but we’re seeing a broader representation of sites actively enrolling in the study and screening.
Scott Braunstein: And Joe, the last comment I’ll make is that I think it’s critical that our team, our clinicians and our site coordinators continue to really make sure that we’re enrolling the right patients and we continue the high standards that we’ve had to date. That’s the only way the study’s going to win and have a decisive victory. And so it’s always a catch 22 in that regard. But I have all the respect in the world for our clinical team and our physicians and our MSLs who are out there educating but not bending the rules to enroll patients just so we hit the numbers faster. That’s always the balance when you run a study like this. Joe?
Joseph Hulihan: And Scott, you mentioned safety. Yes, I neglected to mention, the safety looks good, consistent with the Phase II. We’re not seeing any new safety signals. So that’s looking favorable.
Operator: Your next question comes from the line of Joon Lee of Truist Securities.
Joon Lee: I just want to confirm that at 82 patients, the study is 94% powered to detect a 40% effect size on the coprimary endpoints, but you haven’t disclosed the stopping criteria. And has the stopping criteria changed over time as you look at the enrollment, which has been a little slower than expected, given that if you don’t stop at interim, that you can actually spill into maybe a much later time point for the full study to read out.
Joseph Hulihan: Yes, Joon. Thanks for the question. Yes, that’s absolutely right. It’s 94% powered to detect a 40% treatment difference. Actually, we could see statistical significance at a delta lower than that. Down in the range of 25%, we would still see statistical significance. And the stopping criteria are statistical significance. When you do an interim analysis, there’s always a spend in the alpha that you have to do. And that works out actually to have — if we went to the end, it actually would have a minimal impact on the statistical power at the end of the study. But even with a — it’s 0.0293, but that is — and with that, we have 94% power to detect that 40% delta. So again, well-powered at the interim. Very confident about it.
Scott Braunstein: And Joe, the only I’ll add, Joon, to be clear, we have not moved the goalpost at all on that. I think we had very conservative assumptions going into the trial, as I mentioned earlier, not having a good handle on exactly what the placebo rate would be. We conservatively thought about a placebo rate 30% or higher. And that’s clearly, at least what we believe to be the case today, a much — we’re seeing a much lower placebo rate, which just, in our minds, gives us a lot more flexibility in terms of hitting statistical significance. But we have not moved the goalpost at all in that regard.
Operator: Your next question comes from the line of Charles Duncan of Cantor Fitzgerald.
Charles Duncan: Congrats on the progress commercially. Appreciate the comments on placebo rate and stringency for RAISE, as well as discontinuation rate for TrustTSC. All good, but I didn’t want to talk about that. I wanted to talk about the MAPs program. So I had a question on MAPs. I guess I’m kind of wondering what was the driver for the MAPs program? Was it patient or prescriber request? Or was it your opportunity identification? And can you give us a sense of the financial terms with Durbin? How much, call it, dollar of sales or dollar of revenue will you retain?
Scott Braunstein: Thanks, Charles. Really appreciate the question. Since the launch of ZTALMY, we routinely, more than once or twice a month, receive requests from patients, families, physicians outside the U.S. about access to ZTALMY. And so much of what we do is spending time with not only the IFCR in the U.S., but the CDK alliances in Europe and in other countries and our efforts with the Chinese CDKL5 alliance, for example, has not only helped us understand just how big that — how many patients are in China, over 600 that have been identified and growing, and certainly has driven the orphan disease status and the priority review from the Chinese government. So we are in constant discussions with our alliance groups around the world.
And I think it’s critical for us to help provide the drug to those patients, families and advocacy groups. So first and foremost, that was our goal here. Secondly, I think we’re in a position now with our supply that we can really think about a global expansion. I mean, that’s a critical piece of this. We’re very comfortable with the 2-year shelf life. And those — all of those processes get a little bit more complicated as you go global. So I think we’ve made tremendous progress in our supply chain and our comfort level of supplying drug. And I think we’ve had a lot of inbound interest in that regard from companies to partner with. And so maybe T.J., I’ll flip it over to you and Steve, if you have any comments to talk a little bit more about the economics and how we’re thinking about pricing.
Thomas Lyons: Thanks, Scott, and thanks, Charles, for the question. We are — Durbin, as we mentioned in both the release and in the conversation today, has a lot of experience in this space in EAP. And we’re relying on their guidance on the pricing, where we anticipate we’ll fall somewhere between EU pricing and — projected EU pricing and U.S. pricing on a country-by-country basis. So that’s our pricing trajectory at the moment, yet to be finalized. And with respect to the proportion that we would retain, it would be — it would be a significant majority of the top line, net transaction fees from Durbin.
Steven Pfanstiel: Charles, this is Steve. I would just add that Durbin’s an important partner, but they’re really administering the program on our behalf. We aren’t disclosing the fees in detail here, but they make up a low percentage of the overall revenues expected.
Operator: Your next question comes from the line of Marc Goodman of Leerink Partners.
Marc Goodman: Yes. With respect to ZTALMY, I was wondering if you could just give us a flavor for the gross to net in the quarter and how to think about it into next year. And now that you’ve been out there a while, can you give us a sense of the number of patients that you think are truly there, the CDD patients? What’s the big number there that we can get to that’s reasonable, you know where the patients are and you feel pretty good that those are attainable. And are you seeing any off-label in the 140?
Scott Braunstein: Thanks, Marc. Steve, do you want to start with gross to nets?
Steven Pfanstiel: Yes, sure. Happy to share a little bit of detail there. I think the gross to net deductions have been pretty consistent with our expectations. We’ve always said around 20%. It’s actually been a little less than 20% over the course of the year on a year-to-date basis. We do see that the gross to net deductions coming down slightly. We have about 50% of our patients on Medicaid as their primary, the other 50% commercial. But of that 50% commercial, about 25% have secondary Medicaid access. As they get through their deductibles, that Medicaid secondary drops off, and we see a little benefit from a gross to net. But they’ve been really consistent, just below about 20%.
Scott Braunstein: Marc, let me make one or two comments before I pass it over to Christy to give you a little more color. I think we’ve always said, we believe there are about 100 newborns a year, about 2,000 pediatric patients. The third-party hospital — or the third-party ICD-10 codes certainly are suggesting that there’s well north of 800 patients today, and that number is growing. And remember, this code’s only been around for 3 or 4 years. I will tell you, we still know many of our centers of excellence still don’t use the ICD-10 codes. So we certainly know there are more than that number of patients out there coming into the population. I would say the biggest thing we’ve seen is — that’s different from the time of launch is we have seen adults being treated for the disease, which has been a nice upside to how we thought about the market.
