Sorry, everyone. I lost track of the time and I thought we had extra time.
It is busy.
Yeah. Well, my name is Gena Wang. I'm c overing SMID Cap Biotech U.S. Welc ome to Barclays Global Healthcare Conference. With me today is Doug Ingram, President and Chief Executive Officer from Sarepta. So, Doug, maybe you know we just had a breakfast this morning. Yeah, I wanted to start again with, you know, say, the first after earnings call. You know, what is your view on, say, if existing patient population, how the launch trajectory would look like. And then we can talk about the label expansion.
Sure. First, let me say thank you for having us today. Chat with everybody here and anyone online. Let me just say one other thing, if you don't mind, just real briefly. I think everybody knows 2023 was a really eventful year for Sarepta. 2024 is, you know, going to continue to be eventful, event-filled, and maybe the most important year both in the existence of Sarepta, but I believe in the lives of patients with Duchenne muscular dystrophy if we're able to get the label for ELEVIDYS expanded as we are seeking to do. Your specific question is sort of explain the trajectory on ELEVIDYS. Just to remind everybody, I'm sure everyone generally knows this. We were approved in June of last year with a narrow label, 4- to 5-year-olds, and we did $200 million last year.
Let me linger on that for a moment and explain what that means. That number, which is nearly 2 times all the other gene therapies that were recently launched combined, speaks to the ability not only to execute but also to patient demand, to physician demand, the willingness of payers to work with us, and the ability to bring outcomes to patients with Duchenne muscular dystrophy. It's particularly interesting and meaningful when one considers the narrowness of this particular age group. This age group is narrow in that it is 4-5s, but it is much narrower than that still. The reason for that is that it's a unique group of patients. To imagine that a 4-5-year-old is the same population as the 6-7s misses the dynamics. When you're the 4-5-year-old range already is a very narrow group.
Then when you look into that narrow group, you will realize that the significant percentage of them, perhaps half of them, have not even been diagnosed. So when you think of the EPI, half of them aren't diagnosed. Then you think, well, that explains it. Nope, it still goes beyond that. Remember, these families are unique versus other families because they just got diagnosed. They don't get diagnosed at 4 years and 1 day. They're going to get diagnosed somewhere in there, maybe really close to the aging out. What does that mean? If you're a 9-year-old or a 10-year-old or an 11-year-old, your family has been living with Duchenne muscular dystrophy for years. You have become an expert in it. You understand it. You know the trials. You know the potential therapies. You probably know Sarepta very well.
If you just got diagnosed at four or five years old, your family has had this essentially nuclear bomb land in the middle of this family and have to figure things out. A significant percentage of them, I don't know the exact number, a significant percentage of them just disappear for a while trying to absorb what it means to be living with a life-limiting and ultimately life-ending disease. And then when they either resurface or if they don't disappear, they have to go through the process of learning and figuring out what Duchenne is and finding the right resources and finding the right physician and then going through the administrative process and in the case of ELEVIDYS, eventually getting dosed with an infusion.
In light of all that, one realizes that $200 million last year is enormous progress and speaks reams to patient demand, physician demand, ability to work with payers, execution, the very well-running supply chain and the like. It doesn't speak to the prevalence or EPI. We know the EPI and the prevalence brilliantly on Duchenne. We are experts in it. You know, as you know, we've been doing this commercially for seven years or more, and we've been in Duchenne for well over a decade. What that all means then is that before we get our label expanded, which is currently targeted for June 21, we will begin to flatten out on those patients. That isn't surprising at all when one considers what I've just said. It certainly doesn't speak to the prevalent population or the opportunity.
This is far less than 3% of the total patient population that's addressable here. But that sort of explains it. So we will be flattening out. If we were getting approved today, that may not be the case, but we're getting approved to June 21. So that's sort of where we are. And then, you know, if we get an expanded label as we hope to get and as we're asking for, then we'll have a real opportunity to bring this therapy to a much greater percentage of the Duchenne population.
Okay. So like this 50% like kind of, you know, diagnosed, you know, that will be only apply like only will be an issue if it's the younger patient label. If it's older, then all those patients will be captured at a later time.
Right. A lot. Yeah. I mean, a lot occurs then as a result of that. It means that all the patients that were previously diagnosed at 4-5 are present in the 6-7. And the 6-7s are also enhanced by newly diagnosed patients that didn't get diagnosed before. And they also don't have this either. The older patients don't have this unique thing where they have to learn about what Duchenne is and the like. And the race to get dosed doesn't exist if we have a broad population unrestricted by age.
Okay. Good. Now, you know, going back to, say, EPI interaction and then June 21st, what kind of label you were expecting to have, you know, what kind of scenario you would lay out?
So I think everybody knows what we're seeking. What we've submitted a BLA supplement in an effort to treat the broadest number of patients and bring a broader, better life to the broadest number of patients. So we've asked with the label to do a couple of things. One, to remove both the age restrictions in the label, which has been unprecedented. There is no age limitation in other Duchenne muscular dystrophy therapies. And to remove the limitation to the ambulatory status, which again is not consistent with any of the other approvals that have occurred. We've also asked that this, given that our study EMBARK has read out and we believe has confirmed the benefits of ELEVIDYS, that we are asking that the approval that we have transform from an accelerated approval to a traditional approval. That's where we are.
We're in the midst of a review process. Obviously we'll know the target action date is June 21. We'll have an answer on our request by June 21.
How likely do you think you will be able to get a non-ambulatory patient in the label?
Well, it's hard to give a statti stical probability, as you can well imagine. We think that there is an enormous justification for it. We have dosed a number of non-ambulant patients. We've dosed patients that are very old, 26 years old, and in the non-ambulant for a very long time. We've dosed very large patients, 80 kg, I believe the largest patient and the most gene therapy ever received. We have not to date seen any differences in the AE rates, which is the issue that one might worry about, or either the kinds of AEs or the rate of AEs in there. If you look at both the science, dystrophin is a shock absorber that protects the muscles. It should work equally well across muscles regardless of where you are in this journey, whether you're 4 or 6 or 8, or whether you've been consigned to a wheelchair.
It ought to protect the muscles that you have remaining. And getting a broad label would be consistent with the statutory schema, the regulations, the guidance, and the like. So that's where we are. And then, you know, it is all going to be subject to review by the division and discussion with the division. And we are obviously in the midst of that process right now.
Okay. So in the scenario you don't get label for non-ambulatory patient, so what kind of additional data set you would need in order to expand to that label?
Well, so I'm only speculating because that has not yet arisen in our discussions with the division. But if one envisioned a world in which we were delayed in the non-ambulatory patient population, then let me step back and say one final thing about why there's a real compelling need for non-ambulatory. Remember, when we think about Duchenne muscular dystrophy, we think about the urgency of this disease. Every single day, patients are losing milestones. They're losing muscle. And frankly, a child will die by this one day of conference. A child in the U.S. will die by the time end of this discussion between us. A child somewhere in the world with Duchenne muscular dystrophy will die. And countless others will have lost milestones. And all of them will have lost muscle. And that urgency is no less applicable. In fact, it's more applicable to these non-ambulatory children.
So that's why we're very committed to the non-ambulatory patient population. Now, if we were getting a delay in the non-ambulatory population, one would imagine that it is not because we need more efficacy data. That would not be consistent with the regulatory precedent or the science. So it would be about gathering more safety exposure for those patients. And the fact is that we are running a non-ambulatory study even as we speak. In ENVISION, we're dosing patients and enrolling patients all the time. And so one would assume that if that was an issue, and again, I want to be clear, no one suggested this yet, the issue would be, you know, gather more data and come back to us, you know, whenever, third quarter, fourth quarter, when you have X number of additional, you know, patients that have been dosed and their exposure.
I would assume it would be not a very long delay if there was a delay. With that said, I do still want to come back to the facts. The facts are that we haven't had those discussions with the division. That has not yet been suggested by them. That's certainly not what we're requesting from the division.
How many like non-ambulatory patient safety data you already submit to the agency?
It's a difficult number for me to know at this point because we're on an ongoing ENVISION. So ENVISION is our non-ambulatory placebo control trial. Obviously, we provide regular updates to the agency, even quite apart from the BLA on safety in that trial. And so I don't know the exact status of it, but I'm assuming between our trial and other studies that we've done in the past, we're probably, you know, tens, you know, 20 maybe patients' worth of data. So a pretty significant amount of data and data that relates to, you know, some of the most potentially compromised patients. And they've done very well. And as I've said before, some of the largest patients, which, you know, from a viral load perspective, are probably the greatest viral load that perhaps anyone's ever received with the gene therapy.
And again, I would repeat, so far we've seen no difference in the safety profile. We've seen no difference in AE reporting from those older patients. They seem to be doing quite well.
Good. And then regarding the PDUFA for the June 21st, you know, how likely do you think it could be a possibility early approval? And also related question, you know, do you expect mid-cycle review? And if so, like when would that be scheduled?
Yeah. So a couple of things. So we have been told from the outset by the agency that they are committed to moving as fast as reasonably possible to review the submission with the goal of bringing this therapy to broader numbers of patients if they agree that the data supports doing so, which is great. And they've told us they've said the same thing to the patient community, which is great. We had assumed that we would have a PDUFA date in August. We were very pleased to find that it is June 21. There is always the possibility that the division could do it sooner than that. I believe that the conservative and thoughtful approach is to assume June 21 so that people aren't, you know, assuming something negative if it's, you know, June 15 and we have not yet heard.
So I think for planning purposes, we assume and others should assume that we're going to hear on or about the PDUFA date or the action date, which is currently June 21. And I'm sorry, you had another question in there.
Mid-cycle review.
So it's interesting. I think I misspoke in a recent conference where I said that we would have a mid-cycle review coming up in the next week or so. That's because if you did the math on a normal BLA, you would have imagined that this is a little more flexible than that. We don't have a mid-cycle, to the best of my knowledge, schedule, but I'm very confident we'll have one along the process. And in the interim period, it's not like there's nothing being done. We're getting regular requests for information and answering requests for information and interacting. So it's very productive right now.
Okay. So then for the mid-cycle review, like, say, and then you think that there will certainly be one. And what will be the discussion you'll have for the mid-cycle?
Of course, you know, I'm only speculating because we don't even have it scheduled yet. But I'll tell you what it won't be. I mean, just to and this is a significant difference. It won't be CMC. There's nothing in this package about CMC manufacturing, which is starkly different than the BLA, which was probably 80% CMC in manufacturing. This is a label update so it's not related to that. So what I would assume in the mid-cycle is going to be, you know, questions about the clinical data and the clinical meaningfulness and the like and the patient population. Sort of that is the kind of the, you know, primary focus of this BLA supplement.
Will you get a very good sense after mid-cycle review that what kind of label you will get?
You know, it's interesting. What the company has to do is very similar to what investors have to do with us, which is we all read tea leaves. And the tea leaves we get typically from the division are actually the questions and the tone and the tenor and the kinds of questions being posed. And then we have to read tea leaves about what that might mean for us. I think we'll have some understanding of the mosaic and where we are after that mid-cycle to really know where you are with respect to labeling. You need the label itself. And that isn't going to come probably for the next, you know, two months or so.
Okay. Will you share with us if you have a mid-cycle review schedule? Will you announce that?
I will likely not announce it or the substance of it, not because I'm trying to hide anything. But you remember I just said a moment ago that we do a lot of tea leaf reading. And there's always a danger in tea leaf reading when you start discussing it publicly. You could read those tea leaves wrong. So what I would prefer to do is unless there was something that was materially different, just complete this review, have the productive discussions with the division, deal with the labeling issue as well as the transformation issue with the approval. And then when we will very dutifully and rapidly announce those results when we get them from the agency, which I currently anticipate to be, you know, on or about June 21.
Okay. Good. And maybe quickly, I know as your partner Roche is in charge of Europe, but can you give some update there? And, you know, what could be the U.S. final label impact, you know, would that be any impact to the Europe decision or Roche decision?
Well, I mean, generally speaking, I think a positive outcome with the FDA is just a good signal around the world. But of course, Europe has a very sophisticated regulatory schema with EMA and CHMP. And they have their own standards. And they'll go through that process. That obviously is Roche's to lead. We're, you know, supportive, of course, very supportive and are kept apprised along the way. My understanding from Roche is that they intend to submit this year. I believe they intend to submit the population is sort of in the three- to seven-year-old range, if I'm not mistaken. And they've been great partners. And they appear to be very enthusiastic as we are about the potential of this therapy.
If they are submitting, I assume 4-7 years or so?
I believe that 3-7.
Okay. 3-7.
I think so. But we'll have to talk to Roche.
Okay. So then what about the outside of the age? Like how would they get to the additional? What additional data you would need to generate?
I believe, and again, this is all subject to Roche. I don't want to speak for our partner. I want to be a respectful partner in that regard. This is ultimately their responsibility. I believe the pathway to the broader label will come from ENVISION, I think. So one of the reasons that we commenced ENVISION was because we understood that outside the United States, there may be the need for a non-ambulatory study as a predicate to approval of the older and non-ambulatory patients. And I suspect that it's going to be a big part of their thesis.
Okay. So now that put ENVISION actually in a more important position now. So maybe, you know, the primary endpoint, the Performance of Upper Limb, was that also agreed upon by the EMA and FDA?
I don't know where we are with EMA. I believe we chose a PUL because we believe and we continue to believe that it will be well received as an endpoint both by the FDA and by EMA, CHMP, and other regulatory agents around the world. It's a well-established, validated endpoint. We also chose it because based on the analysis and evidence we have that it has a good probability of success. So we feel very good about the powering of the study and the approach that we're taking.
Okay. One last question. I think I decided not to use competitive landscape. I think it's pretty clear. But on your Limb-Girdle program. So, you know, with this, you know, fast forward and you do have a Limb-Girdle 2E, you can have used biomarker. And how can you, you know, apply this to the other indications quickly?
Yeah. Just to remind you, this is a really big moment for us and for gene therapy generally. The division has shown an enormous amount of innovative flexibility. We have an N=15 study. We have an external control for Limb Girdle T ype 2E and SRP-9003. And we have a biomarker as our endpoint for approval. That means we can fully enroll this study this year and seek approval late next year. We can take that concept and move it to our other limb-girdles. And we're now going to be able to accelerate development in concert with our regulatory reviewers at FDA and OTP. I think it's really a brilliant answer. So we'll do the same thing with our sarcoglycans next year. We intend to get in pivotal trials with the next two sarcoglycans.
We'll be able to apply this approach, I believe, with, you know, all the other limb-girdles that have a similar feature, which is, you know, restoration of the native protein, the absence of which is causing the demise of these patients. Then broader than that, this is a big signal for gene therapy more generally. I think these are the significant green shoots of progress in this march to an innovative vision for the use of cell and gene therapy to bring a better life to patients.
Okay. Great. Well, thank you very much, Doug.
Thank you very much. I appreciate it.
Thank you.