And then, of course, the event classical PKU patients in the APHENITY study with an introduction of 59% of the placebo-controlled portion, I think, is, again, very supportive of the potential for sepiapterin provide benefits to the full spectrum of PKU patients that being of all ages and all degrees of severity and also reinforcing that patients have demonstrated responsiveness to BH4 in the past, so we can certainly expect a much greater response once this put on sepiapterin.
Jeff Hung: Great. Thanks so much.
Operator: Thank you. One moment for our next question, please and is from the line of Brian Abrahams with RBC Capital Markets. Please proceed.
Brian Abrahams: Hey, good afternoon. Thank you for taking my questions. On the 518 Huntington’s program, I guess two questions. First, I’m curious how your views have evolved and whether there could be a potential path for accelerated approval for that drug based on NFL and/or brain volume? And then secondly, I know there’s an additional cohort of patients that you guys were enrolling, the ones that weren’t presented last year and included early Stage 3 patients. Just wondering where you’re at with that cohort if we might see interim results from less than 12 months’ timeframe in the second quarter as well and your latest thoughts on moving to a 20-milligram dose? Thanks.
Matthew Klein: Thank you very much, Brian, for the questions. So, on your first question, look, I — it’s very clear that FDA as a whole of the neurology division, in particular, has been looking at the accelerated approval path as one that is rational for neurodegenerative diseases where it’s typically many years a very large study needed to register clinically meaningful effect, so they’ll be able to have a biomarker that is likely to predict clinical effect, it makes perfect sense. So, you could have an accelerated approval, get patients who need a drug access to a therapy when you collect that longer term data. Obviously, if it makes sense for neurodegenerative disease in general, it certainly makes sense for a disease like Huntington’s disease, which, of course, is an indolent disease and the efficacy study will necessarily need to be large and long.
In terms of potential biomarkers for HD, we think there are several, as you mentioned, both NFL and brain volume, certainly in a disease of inflammation tires to be able to show a benefit on a marker of inflammation just like NFL certainly should be likely to predict clinical benefit. And similarly, for something like brain volume where the pathogenesis disease is selling to the cell death, loss of brain volume and then symptoms that present itself in ultimate clinical degeneration that you could sell that process, a brain atrophy that certainly suggests you should be able to influence the progression of disease. So, we see those both as potential biomarkers. Of course, it’s going to be a matter of having the data, having the discussions with the agencies as we’d be the first ones through that portal.
But I definitely think that the agency is showing openness to leveraging accelerated approval pathway in the case of diseases like HD, and we certainly would look to avail ourselves of that opportunity. In terms of your second question, that Phase 3 enrollment has gone quite well. In fact, overall enrollment really picked up after we shared the June data. We’re able to reassure both the patients meeting the physician on that you can develop a drug for Huntington lowering that is safe and well-tolerated and has a necessary biodistribution and pharmacodynamic effect necessary for therapeutic benefit. So, we’ve seen excellent enrollment and we will be sharing in addition to the 12-month data in the second quarter, interim data from 12 weeks on the other at patients as well as some of the Stage 2 patients.
So, we look forward to sharing all of those data with you all in the second quarter. Your third question regarding the 20-milligram dose, our view remains as it was when we talked about in June, I think what we’re seeing with the 10-milligram dose and the preferential distribution to the CNS with a 1 to 1.5 ratio of plasma to CSF exposure that we very much believe that 10 milligrams is probably the dose that we need. So, right now, we’re committed to moving forward with 5 milligrams and 10 milligrams and learning more about it. Of course, we do have that opportunity to titrate up to 20 milligrams if need be. But right now, we believe that may be very well be sitting with dose levels that are the right ones to safely achieve the desired or of Huntington protein that can provide clinical benefit to patient.
Brian Abrahams: Thanks so much Matt.
Operator: Thank you so much. One moment for our next question, please and it’s from the line of Peyton Bohnsack with TD Cowen. Please proceed.
Peyton Bohnsack: Hi guys. I guess for us, could you possibly elaborate on the reauthorization process for Translarna in Brazil and Russia? And maybe the process for national assessment in the United Kingdom. It looks like in Brazil, specifically, the renewal is up in April. Is that the case? And do you expect — I know you mentioned earlier that there was a crosshead between the two agencies. But do you expect the recent EU decision would have any implications here? Thanks.
Matthew Klein: Thank you for the questions. So, as you mentioned, we’re up for reauthorization of Brazil. That process is ongoing. Every indication we have is that this will continue to be an independent assessment. They remain very interested in following their own assessment of the new of KOLs and others in Brazil and are not influenced by the CHMP decision. I’d say that we’re seeing similar things in the U.K. where they also have said that they want to do their own independent national review and a national authorization. So, the signals that we’re getting very clearly is that the strong desire of countries to do their own assessment and not follow the lead of the CHMP.
Peyton Bohnsack: Great. Thank you. And then I guess, maybe just a quick follow-up question. When you’re looking at the open label data, have you guys reached sublime with exactly what the national history like external cohort group will look like with the FDA? Or is that still ongoing?
Matthew Klein: So, Peyton, you’re talking about for Friedreich ataxia?
Peyton Bohnsack: Yes. Sorry for [Indiscernible].
