Joseph Schwartz: Thank you.
Operator: Thank you. One moment please. Our next question comes from the line of Gena Wang of Barclays. Your line is open.
Gena Wang: Hi. Thank you for taking my questions. So I do have, I think, three quick questions. The first one is regarding the PKU program. Since initially was thinking about 505(b)(2). Is that because of the lack of confidence of their IP position that this drug will be very different from Kuvan? That’s the first question. And relatedly, how confident you are on the IP regarding this is a new composition of matter. And then for the PIVOT-HD, I don’t know if I missed it. So have you like exactly what kind of data you would need in order to remove FDA clinical hold. So based on — I think in your prepared remarks, you did mention certain months of the clinical safety data. When I look at the press release, the six months of the clinical safety data demonstrate similar favorable safety profile could support 12-month dosing?
And what additional data that will require to dose more than 12 months? And what dose you can dose like beyond 10-milligram. So that’s the second question. And a quickly last question regarding the Upstaza in AADC. So if you are using current US data for accelerated approval, what additional study you will need to do in order to get a full approval in the future?
Matthew Klein: Thank you very much for the questions, Gena. The first question for — number one regarding PKU sense. Look, I think that was really what more reflection of sensing a very small virtual company and probably looking for what they thought at the time would be the quickest and least expensive development path forward. I think it’s not uncommon for a smaller company to think about the development path that way. I think from our standpoint, the — it’s very clear that it’s a highly differentiated therapy that is much more suited to the 505(b)(1) pathway. Obviously, we’re in a position to have the resources to do the necessary studies and not have to rely on a other NDA and incur that risk of having a state based on the launch of the therapy follow approval.
As we talked about, not only we have a great deal of confidence in how differentiated sepiapterin is and its ability to meet the persistent large on that medical need for PKU patients and as we put some positions, including Ania Muntau on a commercial [indiscernible] summer, a desire for physicians to even switch patients who maybe serve to some extent Kuvan to sepiapterin because of what we’ve been able to show in terms of the large magnitude of clinical benefit. We’ve also talked about the IP here. We obviously have orphan designation. We also have some potential patent extensions that we believe will extend the orphan exclusivity out several years. Your second question on PIVOT-HD. As we had talked about in the past, our discussions with the agency, they said that when they want to just see additional evidence that we can dose at the dose levels we intended in PIVOT-HD.
Those additional data could take the form of non-clinical data. It could also take the form of clinical data. We had made the decision since we were able to conduct this trial in many countries outside of the US and enroll the study outside the US that we would conduct the study, collect the clinical data in the study and then provide those data as we had them to FDA in order to fulfill that need of demonstrating that PTC518 can be demonstrated safely. So once we had the 12-week data, we took those data that we presented. And obviously, since all patients aren’t enrolled at the same time, we had some data beyond 12 weeks. We provided all of that to the agency, and that was clinical data. It included clinical laboratories, included the NFL levels that we had shared at the early adverse event reports, the lack of serious adverse events, the DSMB minutes, letters from the DSMB chair, all of which were shared with FDA.
As I mentioned in the prepared remarks during our discussion in the meeting, the FDA indicated that those data that we had at that point could be sufficient for 12-week dosing in 5 milligrams and 10 milligrams if that’s what we wanted to start now. But obviously, the goal here is to think about longer term dosing, as your question suggested. And they said that they would like to see those data at the six-month time point, so basically a little bit longer than 3 months to support the duration of dosing that we had proposed in PIVOT-HD. For right now, quite simply, doing the timing math is very possible. By the time we got that data, sent it to the FDA, got the review, got sites ready up and running in the US, it might very well be that we’ll be done with enrollment in PIVOT-HD.
We’re extremely close right now to completing enrollment in the Stage 2 patients, but enrollment is moving very quickly overall for the study, particularly after the gene data release, when we were able to provide a lot of comfort to physicians and patients that unlike other [indiscernible] therapies, we were able to achieve our objectives and do so safely. There’s been a lot of interest in that study. There’s obviously a lot of interest in the United States for patients and physicians, so we would love to be able to open sites here, but if the study is fully enrolled, then we’ll look to start Phase 3 here and be able to offer the opportunity for patients to participate in the PTC5181 development. Your third question was regarding Upstaza and accelerated approval and confirmatory study.
So we are using the existing clinical study now in the US and we have the endpoint that we’re using to support the accelerated approval is an early endpoint of biochemical changes. Then we’ll have a longer term extension component of that study, which will collect long-term clinical data to provide the clinical evidence necessary to support the full approval. So this is really an example where we will have the study ongoing. It’s going to be a long-term study that’s going to look at the acquisition of motor developmental milestones over time, much in a way that we’ve been able to show previously in the clinical studies of Upstaza that were done previously, where over time we’re able to show that these children develop the ability to first lift their head and be able to sit, crawl, and walk independently.
That obviously takes many years, which is why in many ways this is a very good setup for an accelerated approval where we have biomarker evidence, dopamine increases, which is obviously likely to predict long-term clinical benefit of the acquisition of dopamine related motor milestones.
Operator: Thank you. One moment please. Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is open.
Paul Choi: Good afternoon and thank you for taking our questions. Two questions for me. First, on the commercial side, with the approval of Vamorolone today, can you maybe just comment on how you’re thinking about the impact to Emflaza, and would you maybe consider pulling back on Salesforce resourcing for that product starting next year ahead of your expected loss of exclusivity? And then on the pipeline side, can you maybe comment on what you would intend to present in terms of your PIVOT-HD update next year? Should investors continue to expect plasma Huntington updates and neurofilament changes, or would you perhaps present some details on other endpoints, including clinical endpoints? Thank you very much.
