BioCentury This Week
BioCentury's streaming commentary on biotech industry trends, plus interviews with KOLs.
For three decades, BioCentury has helped biopharma executives and investors make business-critical decisions and build larger networks with peers across the innovation ecosystem.
BioCentury This Week
Ep. 310 - Sarepta & What's Next for Gene Therapy. Plus: Leading FDA's CDER
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Last week’s public disclosure that a gene therapy from Sarepta had caused a third death led FDA to ask the company to stop distributing its DMD gene therapy Elevidys, a move the biotech has resisted. The deaths, and disputes between FDA and Sarepta, raise questions about the future of AAV gene therapies, as well as the future of FDA’s platform technology designation. On the latest BioCentury This Week podcast, BioCentury’s analysts unpack the events surrounding Sarepta’s gene therapies and discuss how FDA, industry and patient groups should come together to learn the lessons from the tragic, avoidable deaths.
BioCentury’s analysts also assess Monday’s appointment of Stanford professor and biotech executive George Tidmarsh to lead FDA’s Center for Drug Evaluation and Research, and check in on the latest trends in venture financings. This episode of BioCentury This Week is sponsored by IQVIA Biotech.
View full story: https://www.biocentury.com/article/656537
#biotech #biopharma #pharma #lifescience #GeneTherapy #AAVTherapy #Sarepta #Elevidys
00:01 - Sponsor Message: IQVIA Biotech
02:03 - Gene Therapy
17:59 - Leading CDER
27:00 - Venture Report
To submit a question to BioCentury’s editors, email the BioCentury This Week team at podcasts@biocentury.com.
AI-generated transcript.
Alanna Farro:BioCentury This Week is brought to you by IQVIA Biotech. For biotech companies striving to bring innovative therapies to market and maximize patient impact, IQVIA. Biotech is the trusted CRO of choice backed by 25 years of unparalleled experience and deep therapeutic expertise. Our full service clinical development solutions are purpose-built to accelerate success. IQVIA Biotech helps early stage biotechs de-risk by developing strategic clinical development plans, guiding drug candidates along the most promising pathways, leverage data-driven models and dynamic tools to craft a compelling value story, attract investment, and maintain momentum through every phase of drug development. Last week public disclosure that a sarepta gene therapy had caused a third death led FDA to ask the company to stop distributing its DMD gene therapy. A move the biotech company has resisted the deaths and disputes between FDA and Sarepta. Raise questions about the future of a a V gene therapies.
Jeff Cranmer:The therapy Elevidys was the first and only gene therapy approved for the fatal neuromuscular disease on the latest BioCentury. This week podcast BioCentury analysts take a look at what the death means for the future of gene therapy plus. At long last FDA has selected a new director for CDR, what do we know about Stanford's George Tid Marsh? We'll also take a look at some numbers out of the world of venture financing for biotech. I'm Jeff Cranmer, and joining me today on the BioCentury Podcast are my colleagues.
Simone Fishburn:Simon Fishburn, editor in chief.
Steve Usdin:Steve Den Washington editor.
Selina Koch:And Selena Koch, executive editor.
Jeff Cranmer:Okay, Steve, I, I wanna jump right to you. A lot has happened in the past few days between FDA and Sarepta regarding Elevidys, since the disclosure of the third death of a patient. in a Sarepta gene therapy trial, can you bring us up to speed?
Steve Usdin:So, yeah. So, okay. So on, July 16, that would be like. Last Wednesday, Sarepta announced a major reorganization laying off 500 employees, about 36% of its and shifting its focus toward early stage siRNA projects. It also updated V and added adding a black box warning. That's a similar to labels that are on other a a V gene vectors warning about potential, liver toxicity and, fatal liver, adverse effects on Thursday evening. BioCentury, I reported that there had been a third death in a Sarepta trial that has never been disclosed previously. It was a 52-year-old man who was in a trial of a limb girdle muscular dystrophy, gene therapy, from Sarepta. He uses the same vector as, Sarepta's DMD therapy. The next day, other reporters picked up on that, um, expanded it, and, investors, picked up on it. Also, there was a lot of controversy. Sarepta, issued a statement, had analyst q and a in the statement. And the q and a. They defended their decision to not, disclose the third death, previously, So on Friday, there were several actions that came out of FDA. They, uh, placed a hold on all of Sarepta's limb girdle muscular dystrophy trials. They asked Sarepta to stop, distributing, Elevidys, to any patients. the company, which had announced earlier in the week that it was going to stop shipping elevators to non-ambulatory patients because there had been two previous deaths of non-ambulatory DMD patients Refused to stop shipping. Elevidys this on a voluntary basis to ambulatory Duchenne muscular dystrophy. Patients. FDA also revoked the platform designation for the vector that's used in, sarepta's limb, girdle muscular dystrophy, gene therapies, and in Elevidys. So that's where we are today.
Simone Fishburn:Where to start with all of this? Um, I think in a minute I'm gonna bring in Selena. Let's talk a little bit about the implications for gene therapies and a a v vectors. I don't think you've said that to an a, a V vector, but first of all, just clarify. Um, for those who haven't spent the weekend on Twitter or wherever they're, or X or wherever they're getting their information. What is the reason that it hadn't been disclosed? I understand that Sarepta said it's not materially relevant. How has this come to light now? And it seems in a way that this third, very, very unfortunate death has actually just catapulted the whole company into a, a new phase. I mean, it was clearly, as you say, it was having layoffs and things. It was clearly in some trouble, but it, it just seems to have compounded it. Can you talk about that?
Steve Usdin:Okay, so, so how's it come out now? It came out now because I found out about it and reported it. if I hadn't found out about it and reported it, probably somebody else would've, and it would've come out. but certainly not at the time that it did. The company had no intention to make it public. The companies reported it to FDA, so Sarepta told FDA that there was an acute liver failure case that was life-threatening. They reported that, on June 20th, 2025, that was from their phase one trial of a limb girdle muscular dystrophy therapy, and they followed up and notified FDA of the death on July 3rd, 2025. on Thursday morning, Sarepta informed patient advocates of that death, but they didn't announce it publicly. when I found out about it and asked the company about it, they said that they had no intention or no timing anyway, of making, a public disclosure of that death. In their calls with analysts, they said that, they hadn't disclosed it previously and that it wasn't material because they had already. Announced their intention to discontinue that gene therapy. I should also note that Doug Ingram, the CEO of Sarepta said on that call that the fatal events associated with their gene therapies were very, very rare. rare. And in my conversations with, patient advocates, with mothers of children who've had, DMD. They were very concerned by that comment. Been about 140 non-ambulatory patients who've received Elevidys, and, two of them have died. The limb girdle therapy, that caused a death that was in a phase one trial. There were four patients in that trial and one died. That doesn't really meet people's definition of very, very rare.
Simone Fishburn:So I think something that you wrote about, in your story, which I thought got to the heart of it is what? Parents of the patients who've been on these therapies are going through right now, given what you've talked about are not incredibly long odds. I wouldn't call them short odds, but they are quite serious odds. I don't know exactly the time course, from when a a, a patient is given the gene therapy that this kind of toxicity might arise. But maybe you can just channel what you've hearing from the patient community in terms of what they're going through.
Steve Usdin:Well, one of the, parents told me that living with a child who's received. This gene therapy is a 24 7 panic attack. the timing is several weeks to months after, receiving the therapy. We don't know how many non-ambulatory patients have received Elevidys a month, two months, three months out. but some of them cer certainly have. Um, Roche and June said that worldwide there have been about 140 to 150 boys who are non-ambulatory who'd received the therapy. Since its approval in the United States, since its accelerated approval for the non-ambulatory population, that's how many non-ambulatory patients have received it, given the fact that there's always a lag between an approval and when gene therapies start to get distributed. It's quite likely that a substantial portion of those would've been in the last year, certainly. and that's got to be causing, and it is causing, that's what advocates told me. It is causing a great deal of anxiety, among the families of the, of the boys who have received it.
Simone Fishburn:Selena, maybe you wanna jump in now. Perhaps you can extend this conversation to the implications for a a V gene therapies more broadly and that technology.
Selina Koch:Well, liver toxicity from a a v gene therapies that's a known risk, right? This is, not new. and it really has nothing to do with whether a patient is ambulatory or whether they can no longer walk. Right? there's not a biological connection to that distinction. It's like some. False shorthand. So what we know from gene therapies of the past and from this gene therapy is that it's about dose and it's about the state of somebody's liver before they receive the gene therapy. So older patients who have grown more and are way more tend to be non-ambulatory, right? And they need higher doses. I don't know if anybody remembers, but four or five years ago, Astellas reported four patient deaths in a gene therapy trial for a different severe rare disease that causes progressive muscle weakening, right? That was X-linked myotubular myopathy. And those were very young patients, but that disease, you know, over time it involves a liver. So what they realized there is, okay, well if you're having some kind of liver dysfunction before, it's probably not a great therapy for you. But now in that case, they tracked the, the 20 patients who lived for a couple years and they found out it was highly effective. You had, all of those patients were, none of them could sit unassisted before that trial. All of them were on ventilators. Something like three quarters of them came off ventilators. All of them could sit up and some of them could even walk unassisted. in a scenario like that, you take all of that in and you're like, are the risks worth the benefits? you know, maybe, but Elevidys doesn't have the luxury of really strong efficacy data like that. Um, but when it comes to future gene therapies, what does it mean? It means we need to take stock of all of these gene therapies, right? Not just this one. And think about what have we learned across the board about are there thresholds for preexisting liver talk? are there thresholds for weight and dose that can guide who can successfully, you know who is at lowest risk and are the best candidates for receiving benefit from gene therapies.
Steve Usdin:the thing about this one that's so disheartening is that not only were these deaths predictable, but they were predicted, right? it was Anticipated that this could happen when, when Elevidys was approved for the non-ambulatory population, which as you say that again, it's not about the fact that they're non-ambulatory, it's the fact that they're older, they've had the disease longer, they're larger and they need larger doses. But it was predicted that this was a, a major safety risk and they, they went ahead with it. Anyway. FDA went ahead with it. The company went ahead with it. And also it has to be pointed out that there was little of any efficacy data in the non-ambulatory population to support a risk benefit calculation.
Simone Fishburn:Steve, I wanted to ask you, so we know today from, the SEC filing of Sarepta that FDA has withdrawn its platform designation for a a v that it had granted not that long ago actually. perhaps you can talk a little bit about what you would've wanted to see from an FDA on this whole front related to this particular finding, and then what you would like to see from them going forward on this.
Steve Usdin:Well first I think they need to have a lot more transparency. This administration talks a lot about transparency. They need to have a lot more transparency around their decision making. Here in the statement that they put out they being FDA on Friday, they referenced new safety information that it caused them to take the actions that they took. Well. there doesn't seem to be a good case for saying it was new. They knew about this some time ago. The only thing that seems to have been new is the fact that the rest of us found out about it and there was a lot of concern that was raised. So I think there needs to be a lot more transparency around that. And then I think there also needs to be transparency around the approval of the platform designation for Sarepta, for this gene therapy vector. Why did FDA do it? What was the process that they went through in thinking about it and, how are they gonna think about this, um, platform designation going forward? What are the kind of criteria that they're gonna apply for determining what products should get it, what products shouldn't get? And finally I'd say, you know, speaking to what, um, Selena said, you know, the, the other really big concern is, is, is there gonna be an overreaction here, by FDA, by regulators, and almost certainly by investors. and does that, is that going to jeopardize the whole field of gene therapy, in ways that, arguably aren't necessary and that in some ways, you know, mimic what happened. in the past when we had a tragic death, Jesse Gelsinger death, that really, set the field back for a decade, there was really a, like a decade where there was impossible to do, r and d or to get any investment in the field. I think that that would be. Just as tragic as having these, deaths that have happened that were avoidable.
Selina Koch:Whole host of companies who are trying very hard to solve the problem of gene therapies, you know, just getting stuck in the liver. they're trying to bypass the liver and really concentrate gene therapies in the target organ they're interested in. It would be a shame if that research we're unfundable, cause that's the solution we need. For this. I just wonder if there were some investigation into all of these gene therapies so far that was comprehensive and got into the nitty gritty if it might guide us a little bit and, how much retargeting of liver would be a sufficient amount to avoid most of the toxicity, you know, can we get any insight into that?
Steve Usdin:And I think this is a case where really the industry, academics, the patient community, right? And not just the United States, but around the world should come together and ask that question and other questions, and then plot a strategy for answering those questions.
Selina Koch:Yeah. And then on the platform thing, I don't know. It's possible that the platform designation just. Isn't gonna apply anywhere. I mean, Peter Marks had said before he left, he didn't think AAVs were a good use case. Even though you can apply that same vector to other therapies. There's so much bespoke design that happens in the whole thing, like the com combination of the cargo and the vector and whatnot. and so, he had pointed to, gene editing therapies delivered in LMPs as. Possibly the one place where this designation could shine, but, you know, we'll have to wait and see. It's not, not looking like, there's gonna be a, a large number of relevant use cases.
Jeff Cranmer:Steve, final thoughts here.
Steve Usdin:I think that this is a case where we're, we're really gonna have to see whether the patient, community, FDA, and industry, whether everybody can, resist the urge to, to simply point fingers at everyone. Else and plot a, a good path forward. And, and there's a lot at stake. And, and you can't forget that it's, it's right in front of our face, right? the patients, the boys who have DMD still need. Safe, effective therapies, it's still a relentless and terrible disease. that needs to be treated with urgently. There needs to be urgent steps to, to, develop, products that are gonna help them. and there's so many other diseases that potentially could benefit from gene therapy that what's really, really needed now is this kind of, overarching, attempt. to plot a, um, a safe and scientifically responsible path forward, to be able to, to use what's arguably could be, you know, tremendously important therapy and, and, and in other conditions. Of course, gene therapy has been tremendously effective and safe and, and has, saved lives.
Jeff Cranmer:Okay, and that course is the subject of Steve's editor's commentary, that we published on Friday. You can find that at BioCentury podcast.com. We're gonna take a quick break, and then we're going to turn to FDA and learn. About the new CDR director,
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Jeff Cranmer:We're back on the BioCentury This Week podcast. Appreciate you tuning in and if you like what you're hearing, please subscribe and leave us a comment or a question and we'll try to respond on an upcoming episode. Okay, On Monday, FDA Commissioner Marty Macari named Stanford Cancer biologist George Tid Marsh as the new head of the agency's Center for drug evaluation and Research T Marsh completed training at Stanford in pediatric oncology and Neo. Natology and his adjunct faculty of pediatrics and neonatology is founding co-director of Stanford's Master of Translational Research and Applied Medicine Program. He's also founded in bin CEO of multiple Biopharmas, including Horizon, which Amgen acquired for 28 billion a couple of years back. Tid Marsh Succeeds. Jacqueline Corrigan Curry. The now former acting director of CDR, PO. She held since January when, Patricia Cone stepped down from the position. Steve, of course. Uh, as everyone knows, you follow FDA quite closely. What are you hearing about Dr. Tidmarsh?
Steve Usdin:it's really interesting. First, the name came out of the blue. It really surprised a lot of people. It surprised people, senior people at FDA and people who watch FDA closely. He has, as you mentioned, he has deep experience developing drugs and industry. He's trained as a pediatric oncologist. The other thing that you have to know about him is that he's been a very, very strong and adamant supporter of anti-establishment perspectives on COVID-19. and really Dr. McCarey, with, Robert F. Kennedy Jr. The HHS secretary, everything seems to come back to COVID-19 in one way or another, but more on his resume. Okay. So you mentioned that, he has. In biopharma, he was, president and CEO of La Jolla Pharmaceutical. When he was there, he helped, discover and, develop an angiotensin two, drug for the treatment of shock. That was approved. he was founder and CEO of Horizon Pharma. As you mentioned, horizon was, sold to Amgen for 28, billion dollars. He also founded a company called Threshold Pharmaceuticals. And he is held senior positions at Coulter Pharmaceuticals, which was acquired by GlaxoSmith Klein Ceq, and other companies. he led clinical development of Bexar and Doxyl, to FDA, anti-cancer drugs. he is also known as I said, for his, anti-establishment, views on, COVID. He's very, close personally with Dr. McCarey, with, Vinad, the CBER, director and with Jay Charya, the NIH director. he's praised, Robert F. Kennedy Jr. He wrote something, just a month ago, where he attacked former Seber director, Peter Marks, and said that, Mackery and, um, Kennedy were right to have, forced, Marx to resign. He attacked him in particular on his, policies on, COVID and also on what we were just talking about on, uh, Marx's policies on, Elevidys, more recently in April. He published a, a paper calling for a reevaluation of the use of talc in pharmaceuticals and in other products. That paper was published in a journal that Bachar and McCarey founded. interestingly, the paper was submitted on April nine, was published on April 10, which doesn't suggest that there was, a traditional kind of, peer review. and he's, he's been very active in the last couple of years, on the Stanford campus. he, put up the money to pay for a conference last year, about, COVID issues. and he moderated one of the panels there. Ery, Scott Atlas, who was a very controversial figure in, um, COVID, Prasad and others, uh, spoke at that conference. One of the things that I found that was really interesting, in Ted Marsh's comments of the conference is that it seemed to suggest, that he has a, has views about the off-label promotion of drugs. He didn't actually come out and say that, but in some of his questions, it seemed to me that. he was suggesting that he believes that FDA, has been too restrictive, in, um, regulating off-label, comments that, drug companies have made. you know, which is interesting because all of the COVID, um, issues really aren't. Terribly relevant, um, to c you know, vaccines, come under C but if you think about how has his experience, in this, anti establishment COVID world, how is that going to, color or affect the decisions that he makes? At c You could imagine that it might, might happen around, speech issues in general. Promotion of off-label ideas, uh, off-label truthful. a non misleading off-label information could be interesting. Just wrapping up, one other thing that he said that I found interesting when he was kind of talking about his philosophy or his, the way that he looks at the world, he talked a a lot about the fact that some, uh, medicines started out as fringe ideas. Things that people, um, laughed at and didn't think were reasonable and then they ended up. Being approved and, and, and, and proved, right? In some cases people got, Nobel prizes for them. So, it leads me, leads me to think that he's going to bring that kind of thinking Cedar.
Simone Fishburn:It's interesting, Steve, because as you point out, so much of it seems to just always come back to COVID. And I say that because there's also a, a thread in some of the HHS, new, officials that is quite industry adverse or industry suspicious, but that doesn't seem to be the case here. with Dr. Tma, she's as, as Jeff pointed out, he's been a CEO several times. He's been quite in this interface. And so So it's gonna be interesting to see how that sort of tension plays out. Clearly, as you say, he's a favor of what you might call the serendipity or the ones that everybody didn't believe, and they're the ones who, bring the goods in the end. and being more open to that, which I think a lot of people might think that FDA could be more open. There's also this slight grievance oriented. We were treated badly in COVID. Nobody listened to us in COVID angle. That seems to be coloring and maybe dominant among the, the new, new heads. how do you think about that?
Steve Usdin:it's interesting, you know, there, related to that, there's this, there's a lot of tensions right in the way that, the Trump administration thinks about. FDA and public health in general. And one of the, the tensions is between, you know, praising the biopharmaceutical industry, wanting to promote it. saying that FDA, commissioner Ery has said several many times that he thinks that FDA should do, should get out of the way of industry that it, has been too, um, restrictive. And on the other hand, he and HHS Secretary Kennedy, Really vilify industry. And they say that, um, uh, the big pharmas, corrupted FDA, that they've corrupted medical journals, that they've done all kinds of things that Kennedy and, ery think, are nefarious. and, Kennedy said that FDA in the past has been a sock puppet. For industry. So it's really interesting that ery reached out to someone who has got more experience, I think, at a higher level in industry, certainly than anyone else who's ever run CDER. And I actually would be hard pressed to find anybody who's ever worked at, FDA, who's had the kind of, um, senior positions and been involved in the development of so many drugs, as Tid Marsh. and it's interesting also because among RFK junior supporters, the, the MAHA movement, there's already a kind of a backlash of if you look at their websites and listen to their podcasts, some of them are highly critical, for example of in a Prasad and say that, uh, he's not adhering to the precepts of the Maha movement. and they've, they've urged, ery to get rid of him, which I think is extraordinarily unlikely to happen. Ery seems to be, really delighted with Prasad. and the other thing to think about, I think, two things. One is this appointment and Prasad's appointment. They, they represent, a kind of politicization of the leadership of these centers. There's always been a political element to it, but I think that this makes it much more explicitly so and it makes me wonder how long their tenures are going to be. If there's a new commissioner who has a different political agenda and views the world differently, is that commissioner going to change out? The, center directors traditionally, that hasn't happened, but we've seen a lot of tradition go right out the window recently. So, it'll be very interesting to see whether that's the case here.
Jeff Cranmer:Okay, thanks for that. Steve and Steve's story, you'll be able to find at BioCentury podcast.com. And we will be, uh, closely watching, how things, shake out at Cedar. Let's do a little finance. Bio. Steven Hanson recently completed his look at the third quarter public markets, his preview of the third quarter public markets for biotech. You can catch up on that by tuning into last week's BioCentury this week podcast. And on the heels of that, uh, last week our director of research, Meredith Durkin Wolf, assessed how venture financing has been in the first half of the year. Selena, you, uh, edited that and so much more while I was, off traipsing around, uh, Spain eating pincho and tapas and drinking kava and, uh, reluctantly coming back. what did you learn?
Selina Koch:Yeah. Well these were, um, we published a couple of what we called data bytes. These are just small bytes, one chart each, a little bit of dialogue. and the first one I looked at just. Total venture, you know, any series, any disclosed venture in the first half of the year compared to the first half of 20, 24 or 23, et cetera. Going back to 2016. And I think the big thing that stood out to was that the number of venture rounds, was the lowest in that 10 year period. So there was a slowdown in the, Raising of rounds. it was not the smallest first half in that time period for the amount raised. 2016 and 2017 were lower. but that's because it seems the average round size was bigger. which, may not be surprising if you've been following our coverage for a while. it's, you know, the IPN window remains pretty much closed. Companies have to stay private for, for longer. And investors, yeah, are kind of sometimes forced to pick winners and, and to keep funding those and keep those companies moving along private. so that could be one factor behind that, observation.
Jeff Cranmer:interesting. Selena, uh, I'm, I know, uh, Meredith also took a look at seed and Series A financings and curious What we learned there.
Selina Koch:Yeah, similar but different. so if you look at, again, the number of seed and series A rounds in the first half versus other first halfs. It's this been going down and down and down since 2021 with 20 five's. First half being the smallest in the 10 years. Okay, so that part is the same. But the amount raised in the first half actually was more than in 2024. Um, it was pretty, pretty healthy. and then when she looked, you know, into the individual rounds and figured, you know, trying to figure this out, it seems that 25% of the total raised came from four companies. So. Mega rounds. These continue to be a trend. We, we keep seeing them. Uh, so we recorded in BioCentury 35 Cedar Series a rounds of at least 200 million in the past decade. Four of them occurred in the first half of 2025. so that's, that was tying the first half of 23 for the most in any half year. and it was the largest total. From those big mega rounds.
Jeff Cranmer:And what's a mega round? Are we,
Selina Koch:In this case.
Jeff Cranmer:million or where,
Selina Koch:In this case, it was two 200 million or
Jeff Cranmer:we're doing 200 million now. Yeah. Back in the day it was a hundred million.
Selina Koch:yeah. Right. Mega gets getting bigger.
Jeff Cranmer:So, yeah, even, even, it's interesting, even in these, you know, obviously very difficult times for financing. It's, uh, good to see that, the early stage companies still getting funded
Selina Koch:Yeah, well I think the take home is fewer of them are getting funded, but the ones who are getting funded are fund getting funded for a longer runway just because that's what it takes.
Jeff Cranmer:Interesting. Okay, well, those data bytes, uh, up on BioCentury podcast.com or BioCentury dot com, if you're a. Subscriber, you can go there and, uh, access that and appreciate you tuning in. will be back next week, as usual, and, uh, later this week. Don't forget to turn into our sister podcast. later this week we will have president and CEO, John Lapore of profound Therapeutics in conversation with editor in chief Simone Fishburn. Kendall Square Orchestra provides the music for about a century This week, the group connects science and technology professionals. And other members of the Greater Boston community to collaborate, innovate, and inspire through music while supporting causes related to healthcare and education.
Alanna:Would like to thank IQVIA Biotech for supporting the bio this week podcast. To learn more about how IQVIA Biotech can help you turn your vision into venture capital. Go to IQIA biotech.com/visionaries. I.
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