Operator: Our next question comes from the line of Joseph Schwartz with Leerink Partners.
Unidentified Analyst: This is Jenny [ph] on for Joe. I was wondering if you could just talk a little bit more about the 4Q readout for ALS. I think you’ve said in the past that the study could be registrational. Can you give us an idea of what regulators will be looking for to support that? And can you kind of give us some insight into what a clinically meaningful change in ALS functional rating scale would be?
Matthew Klein: Thank you very much for the question rather. So we are designed the CARDINAL study to be, as you said, registration direct and this came from our feedback with FDA, both in terms of relation of the study being roughly 6-month study, placebo controlled and the endpoint strategy, having the primary endpoint being the ALSFRS scale. We define success here as a statistically significant benefit on the primary endpoint which on the ALSFRS scale, that has traditionally been the threshold for agency approval. We powered the study to have what we believe would be a clinically meaningful effect which is roughly 2.5 point difference between the treatment and the placebo group. And we designed the study to be well powered to detect that.
So we believe if we’re able to have statistical significance on the ALSFRS. We also, of course, have secondary endpoints capturing other important aspects of the disease, including mortality, including respiratory function, where we, of course, will look for supportive data of that ALSFRS scale, we believe that will position us to advance for approval in the U.S.
Operator: Our next question comes from the line of David Lebowitz with Citi.
David Lebowitz: To this point, have you really significantly felt the presence of generic Emflaza or of a recently approved of
Matthew Klein: David, thank you very much for the question. As we talked a bit about on the call, we put a lot of strategies in place to preserve the Emflaza market, even in the competition, the Kylie talk a little bit more about what we’re seeing in terms of dynamics.
Kylie O’Keefe: Yes, absolutely. I think, David, the answer — the quick answer to that is no. And I think that’s a testament to the strategies that the team has put in place to protect the business. And as we said in the first quarter, they’ve been executing upon that. I think what’s really been a strong message for us is the continued new patient starts and we’ve seen an incredibly large number of new patient starts in the first quarter. And I think that’s a testament to the loyalty to Emflaza and the continued benefit seen by both patients and physicians.
Operator: Next question comes from the line of Danielle Brill with Raymond James.
Danielle Brill: I have two brief ones. First, to clarify on Translarna status in the EU. Is it possible that the delay in the EC ratification of the CHMP opinion is procedural? Or was this meeting this week specifically called because the EC is considering not ratifying the decision? And then on — the second question is about the in the EMA. I believe EMA feedback on the feasibility of a conditional approval was expected in 1Q. Any updates on that front?
Matthew Klein: Yes. Thanks, Danielle, for the questions. On your first question, the typical procedure is 67 days. Usually, this is done by writing. It’s usually written agreement across the member states and that then allows for the ratification by the EC. That procedure, we know was a pause instead a live meeting was called for discussion, what the exact nature of that discussion was what motivated that discussion we can’t say. What we can say is the typical EC adoption occurs within 67 days we’re clearly beyond that time point. It’s typically a written procedure. They’re having a lot of meetings. So there’s a lot of things that are going on now that are really atypical. What that means in terms of the ultimate EC decision, whether to adopt the opinion, the matter back to the CHMP, whatever that the decide.
We can’t say what we can say is we’re far beyond what we had expected and what was typically observed and the procedure has not gone according to what typically happens. In terms of your question on vatiquinone, we had previously shared that we had got a feedback from the EMA from — we have gone through the scientific advice procedure, they did not indicate that they thought that the move that Phase study could support conditional authorization at this time. We’re looking forward to further discussions with them. And of course, on the FDA side, we have the a different experience where after we had a recent meeting with the FDA in Q1, we are moving forward with the NDA based on study as well as open-label extension data book from the older study performed a few years back as well as from the MOVE FA long-term open made extension.
Operator: Our next question comes from the line of Tazeen Ahmad with Bank of America.
Tazeen Ahmad: One on FA. Can you just talk to us about the patient population, how different it might be in the U.S. versus EU in terms of sizing? And then secondly, for Huntington, based on the conversations that you’ve been having so far with the agency, what’s your level of confidence that a biomarker can be used at least as an end point, maybe not the sole endpoint? Is that topic has been brought up in recent discussions?
Matthew Klein: Thank you very much for the questions, Tazeen. In terms of populations for FA, it’s roughly similar sized population prevalence in the U.S. and in Europe. Clearly, in the — in both territories, there’s nothing indicated for patients under the age of 16 and we talked a lot about how the data from FA really supports the important treatment affecting that population with regard to delay in time of lots of ambulation. And obviously, that has applicability beyond just the under 16-year-old patients, the effects we observed in our ambulatory [ph] patients with So population is roughly the same size. We see an ability to fill the unmet need in the pediatric population but also potentially have an important, important effect for all ambulatory patients regardless of their age. I believe your second question was on biomarker and HD as an endpoint. Is that correct?
Tazeen Ahmad: That’s right.
Matthew Klein: So the — we have not had discussions yet with the agency regarding biomarker accelerated pathways and biomarkers role in the endpoint strategy. I think we’ve clearly seen that the agency, particularly the neurology division has been looking to leverage the accelerated approval pathway for neurodegenerative diseases like Huntington’s disease, like Alzheimer’s disease, we’re collecting that definitive efficacy data in a Phase III trial takes many, many years. I think the challenge we have in HD, of course, is there’s no precedent yet for what that accelerated approval biomarker would be. We believe that the PIVOT HD study offers several important biomarkers, including peripheral Huntington particularly with the systemically administered drug.
And obviously, we talked a bit about the potential for NFL levels which has been used in the case of the first in for ALS and then also things like Huntington protein and the CSF. So what we plan to do is collect data and begin to have discussions with the agency once we have data in hand of what a path using biomarker data or what would be as you asked, the role of biomarker data in establishing the efficacy of the therapy for Huntington’s disease but we think there certainly should be an appetite just based on the agency’s recent activity.
Operator: Our next question comes from the line of Paul Choi with Goldman Sachs.
Paul Choi: I have two and my first is just with regard to the CARDINAL trial and ALS. In the wake of the recent PHOENIX study results from AMLIC. Have you either implemented or contemplated any study design changes or changes to the statistical plan just based on the recent PHOENIX results and just what your thoughts are there? And then second, just a follow-up also as well on HD and PTC518. Can you maybe just comment on the — with regard to your regulatory discussions just on the safety side for U.S. sites and any progress that may have been made there.
Matthew Klein: Thank you for asking the question. Your first question regarding CARDINAL. When we — the FDA has been quite clear on what they want to see in terms of analytical approaches for the ALSFRS. They’re very interested in understanding changes in score as a continuous variable. They’ve also been interested in understanding mortality and the time to mortality. And specifically, we talked about wanting to understand the difference in scores between treatment and placebo and then also implementing something called a joint rank test which is a way of analyzing together both the change in ALSFRS score as well as patients who may have died and the information of their timing of death following enrollment. So we’ve, of course, taken the agency’s guidance to ensure that our analysis plan was consistent with what they want to see.
And that doesn’t change with anything regarding the We work closely with the agency in designing the study to ensure that it would be registration directed and ensuring that we have the appropriate analysis plan so that when we get the results, if they’re positive, that we’d be well positioned to advance the drug towards approval. Regarding your question on safety data from PIVOT HD and discussions with the agency. As we prepare for the second quarter data disclosure, we will then have the safety data that the agency has asked to review in order to lift the partial hold. So we look forward to submitting those data to the agency when available. Just as a reminder, they had asked us following the last data review of 12-week data to provide them a 6-month data on the sufficient number of subjects that would confirm what we’ve seen at 12 weeks.
Well, clearly, we’re going to be in a position to provide the agency not only 6-month data but 12-month data on a number of patients. And as we’ve shared, we’re continuing to see the drug to be well tolerated. So we look forward to putting that data package together, submitting it to the agency and hopefully to lifting a partial hold in the near future.
Operator: And at this time, I’m showing no further questions. I’d like to hand the conference back to Dr. Matthew Klein for closing remarks.
Matthew Klein: Thank you all for joining the call today. Clearly, we’re very excited about the outstanding performance in the first quarter, both in terms of revenue and execution across all of our programs. We are well positioned to continue this success throughout the remainder of the year and look forward to updating you all as we move forward. So thank you all and have a good evening.
Operator: And this concludes today’s conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.
