Also as part of a conditional marketing authorization, as we’ve done for years, requires an annual renewal. For the past several years, we’ve done that. And that’s — a lot of that is relied on the continued evidence of safety you’re seeing in STRIDE as well as benefit that you’re seeing in STRIDE. There are therapies that have been, have had conditional marketing authorization status for decade, 2 decades. So this would not be the first time that a therapy continued in a conditional frame for a bit more time. On your second question regarding the pre-BLA meeting and the issue of comparability. So comparability analyses are done to show that the material that we use in the clinical studies is as similar as possible to the material that we intend to use commercially.
And usually that includes, as you referred to a number of different analytical assays. One of the challenges that we had is that the clinical trial material that we, for which we had to establish comparability with the commercial process is over a decade old. Those are clinical studies that were started in the early 2010s. And there simply is not enough of that residual clinical supply available to provide the additional replicates and additional data that the agency wanted us to have to finalize the comparability analysis. We obviously had data across all the assays that we believe show that the process is comparable. We’ve asked for some additional analyses and it’s a bit challenging to get that material given the age of the material. Now, importantly, we were able to discuss with them the potential to leverage the accelerated approval pathway using our ongoing study in the U.S., which is using material made with the commercial process.
So it is the commercial-like material for which there was no comparability assay. And what we’re able to show in AADC, which is a genetic disease of dopamine deficiency, is that when we give the drug, we’re able to measure increases in dopamine. Obviously that’s a reliable, quantifiable biomarker that’s not only incredibly important to the disease pathology, but also logically will precede the subsequent development of dopamine-related motor function, which is exactly what we observed in the clinical study. So that fits squarely in the framework of accelerated approval. And I think everyone has seen lately in fever, there has been increasing interest, Peter Marks has talked about this ahead of CBER of using the accelerated pathway for rare disease gene therapies as a way to quickly get these therapies to patients.
So we’re looking forward to a pre-BLA meeting in December. So they asked us to do that to make sure we’re aligned on the contents of that accelerated approval BLA package and then pending the outcome of that meeting, you’d expect us to get the BLA shortly thereafter.
Operator: Thank you. One moment please. Our next question comes from the line of Brian Abrahams of RBC Capital Markets. Brian Abrahams, your line is open.
Brian Abrahams: Hey, good afternoon. Thanks for taking my questions. As you prepare for the MAA filing for sepiapterin next year, what are your expectations for what the CARC study requirements will be for Europe approval? And then secondarily, I guess, on Translarna in the US, where do you stand in terms of key discussion items and potential areas of focus that you’re expecting for the Type C meeting? And when might we see an update from that? We’ll be shortly after the meeting or should we expect a little bit of a time gap to allow for the minutes to be collected? Thanks.
Matthew Klein: Thanks for the question, Brian. So on the question regarding the MAA in Europe, I think this is another example of how regulatory authorities tend to look at things differently. The feedback we have gotten from Europe regarding carcinogenicity is they understand very well that the active metabolite for sepiapterin is BH4. And they understand that BH4 and sepiapterin are both naturally occurring cofactors. They understand the data we’ve collected to date in terms of carcinogenicity risk. And they have said, they would like us to not only have our own data, but that we can rely on the data and the experience include Kuvan for many years, there’s a knowledge base that exists that there’s been no carcinogenicity risk associated with BH4 used clinically for many years.
So we don’t believe that the issue we have at FDA will be an issue with Europe for that reason. So again, different authorities looking at things differently. And again that’s why we’re able to move forward with that submission as we said in the first half of 2024. On your question regarding the Type C meeting for Translarna, the purpose of that meeting is really to focus on the evidence that we have, the many sources of evidence we have showing that not only there’s clear evidence of benefit in studies such as Study 041, but that could be confirmed in a number of ways, including meta-analysis, the long-term real-world STRIDE registry. And so really working constructively with the division to say, what are the components we need and how do we formulate them in order to support the end of the submission?
As we typically do, once we have clarity in the outcome of the meeting, sometimes that can come from the meeting itself, sometimes that requires minutes, sometimes that requires some back and forth afterwards. As soon as we have clarity, we’ll certainly share it. Obviously, we know a lot of people are quite interested in the outcome of this meeting, not the least of which are the boys in nonsense mutation DMD in the US who have waited years for therapy. And then also the large number of boys in the US who’ve been on Translarna for a number of years for their participation in clinical studies and beyond, all of whom are quite interested in ensuring that this drug can be available in the US for them.
Brian Abrahams: That’s really helpful. Thanks for that.
Operator: Thank you. One moment please. Our next question comes from the line of Colin Bristow of UBS. Your line is open.
Colin Bristow: Good afternoon. Thanks for taking the questions. On the sepiapterin NDA filing timeline, I am just curious, what is the latter end of your guidance 3Q 2024? I am curious, can you confirm whether the study has started? And it just seems like a sort of extreme upper bound of this timeline if this study is all that’s needed. And then on the AADC, could you just put a little more detail on why FDA thinks the comparability data is still not sufficient? And then what are you sort of hoping or what will be discussed at the pre-BLA meeting in December? Thank you.
Matthew Klein: Thanks for the questions Colin. So — the — if you just — when you find out you have to do a study, it takes a little bit of time to actually organize the study, get the slide at the CRO, get the animals ordered, get the doses confirmed, get the protocol set, get the protocol agreed upon and start the study. We expect to begin dosing in the study, have all those things ready and dosing that study to start in December. That’s a six-month study. So by the clock that all the animals get dosed in December, that’s the in-life portion should be done in June. Once the in-life portion is done in June, they have to sacrifice the animals, go through the histological studies, all the histological analysis and write their report.
