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Third patient dies from acute liver failure caused by a Sarepta gene therapy
- OsrsNeedsf2P 1y agoTheir stock is down 90% over the last 6 months, 37% today. That's not good.
- NooneAtAll3 1y agostock price barely mean anything in recent years
- financetechbro 1y agoNot for biotech. The stocks in this segment are very sensitive to trial outcomes and drug efficacy
- bboygravity 1y agoStocks in biotech also very sensitive to coordinated naked shorting and cellar boxing by hedge funds.
- NooneAtAll3 1y agoif anything, that's stocks *getting meaning* and crushing from dreams down to earth stocks don't have real value anymore
- deleted 1y ago[deleted]
- simmerup 1y agoDamn, gene therapy is so promising too
- barbarr 1y agoThe issue was not the gene therapy itself, but the delivery mechanism. They used a virus to administer the gene therapy, and this virus (like most bloodstream impurities) aggregates in the liver. At low doses this is fine, but at high doses, your body's immune response will be laser-focused on the liver, and you die from the side effects of this response.
- cyberax 1y agoLipid nanoparticles have exactly the same problem. They mostly concentrate in the liver.
- bgnn 1y agoWouldn't anything concentrate in the liver?
- amelius 1y agoCould hemodialysis prevent this?
- EA-3167 1y agoYes, dialysis is surprisingly good at filtering out viral particles, but... that's not desirable in this case. After all these viruses are carrying the therapeutic payload, if you filter them out then you might as well not introduce them in the first place.
- actionfromafar 1y agoBut maybe as treatment if liver problems are detected?
- EA-3167 1y agoI suppose it's possible at that point, possibly to try and stem the process. The question is just how rapidly this condition emerges, and I suspect (although this is just a suspicion) that the time between onset and a severe reaction is fairly brief. Mostly though the problem is that this is a really complex, whole immune system reaction that's triggered by the AAV in the liver, but simply removing the intial cause probably wouldn't stop the cascade. I took a look at some of the aftermath reports (i.e. https://pmc.ncbi.nlm.nih.gov/articles/PMC10638066/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10638066/ and some others) which get into specific details about the course of treatment in several patients who died from this complication. The through-line is an aggressive use of several immune suppressing and modulating therapies to calm the cascade. I have to admit I can't find any specific discussion about dialysis in that context, so I can only assume that removal of the viral particles would be a case of closing the barn door after the horse escaped.
- fsckboy 1y agothe paywall really cuts down on the readability of this story. a quick google showed plenty of news stories though, their shareprice dropped 40% on the market today. I'd be curious what the numbers are for the "good" that this therapy does; is there any way that this therapy is still "worth it" at any scale? but I know little about this area so that's a fairly naive question.
- mandevil 1y agoThe answer is, the therapy does not improve much. It was controversial when it was approved, because the Phase III clinical trial failed to show statistically significant improvement- lots of people in the FDA advocated against approving the drug (even without knowledge of these rare fatal side effects) but were overruled by Peter Marks, head of the the biologics for the FDA under Biden. It seems to me to be similar to the approval of the three Alzheimer's drugs which don't really show improvement either- it seems like over the past decade the FDA has wanted to approve drugs that might work for diseases where there was no treatment at all (while saying things "delivering hope"). And it's not gone well, and has not been a good idea.
- forgotpwagain 1y agoA thread from yesterday about why gene therapy hasn't reached its potential: https://news.ycombinator.com/item?id=44573193 https://news.ycombinator.com/item?id=44573193
- trhway 1y agoInteresting point there: "The other problem is with viral vector based gene therapy is you can’t have it again. You develop antibodies which prevent it from working again, and it could cause a dangerous immune response." Just wondering - would it make sense to immune-suppress the patient for a short period of administering of the viral-based therapy. And as they describe that most gene therapies affect only extra-nuclear DNA, and thus have no permanent effect, wouldn't mRNA work better then in such cases - naturally the tech wasn't there 10+ years ago, yet today thanks to COVID it is here. Edit (due to posting rate limit) in response to comment below: I was thinking about mRNA coding dystrophin like it was coding COVID protein - should be cheap and easy (well, for some definition of easy in that context) doable, and it would be like a weekly self-injection - no toxicity, etc. Of course fixing the issue once for life would be better, once such cure becomes available, yet for now it would be similar like diabetics have with insulin - hassle for sure, yet it works.
- leereeves 1y agomRNA vaccines like the Pfizer and Moderna COVID vaccines don't enter the nucleus nor have a permanent effect. The mRNA breaks down after a few days.
- stefantalpalaru 1y ago[dead]
- msandford 1y agoDo we have any studies that show this fast clearance? From what I understand at least one of them used a pseudo-uradine that there isn't an efficient direct metabolic pathway to process, which was kind of the whole point. The idea being it would circulate longer and be "more effective"
- sampl3username 1y agoSarepta's drug uses AAV to deliver the payload. I wonder why they chose AAV instead of lipid nanoparticles. https://medcitynews.com/2025/07/sarepta-gene-therapy-fatality-limb-girdle-muscular-dystrophy-ingram-srpt/ https://medcitynews.com/2025/07/sarepta-gene-therapy-fatalit...
- ceejayoz 1y agoProbably because the HHS secretary is vehemently opposed to lipid nanoparticles. https://www.axios.com/2025/04/18/rfk-jrs-potential-future-targets https://www.axios.com/2025/04/18/rfk-jrs-potential-future-ta... https://kffhealthnews.org/news/article/nih-grants-mrna-vaccines-trump-administration-hhs-rfk/ https://kffhealthnews.org/news/article/nih-grants-mrna-vacci... > National Institutes of Health officials have urged scientists to remove all references to mRNA vaccine technology from their grant applications, two researchers said, in a move that signaled the agency might abandon a promising field of medical research.
- SoftTalker 1y agoThey've been working on this for years. It's not anything to do with the current administration.
- downrightmike 1y agoYeah, if not for Germany, the covid vax wouldn't have been unreachable.
- barbarr 1y agoI'm guessing they were looking for preferential delivery to certain cell types, and AAVs just happened to have best profile for those. If anything, LNPs might aggregate in the liver even more than AAVs, which can lead to even worse hepatotoxicity if an immune response happens.
- sampl3username 1y ago
- Flux159 1y agoA bloomberg archive.ph article about the same topic - https://archive.ph/9qB0t https://archive.ph/9qB0t
- DangerousPie 1y agohttps://www.science.org/content/blog-post/sarepta-sarepta https://www.science.org/content/blog-post/sarepta-sarepta Thoughts from Derek Lowe (In The Pipeline).
- perihelions 1y agoAlso Derek Lowe's previous ones as context (subset I could quickly find), https://www.science.org/content/blog-post/sarepta-s-approval-woes https://www.science.org/content/blog-post/sarepta-s-approval... ("Sarepta's Approval Woes" (2013)) https://www.science.org/content/blog-post/sarepta-s-duchenne-therapy-lot-further-away https://www.science.org/content/blog-post/sarepta-s-duchenne... ("Sarepta's Duchenne Therapy Is A Lot Further Away" (2014)) https://www.science.org/content/blog-post/sarepta-s-day-fda https://www.science.org/content/blog-post/sarepta-s-day-fda ("Sarepta's Day at the FDA " (2016)) https://www.science.org/content/blog-post/sarepta-gets-approval---unfortunately https://www.science.org/content/blog-post/sarepta-gets-appro... ("Sarepta Gets An Approval - Unfortunately" (2016)) https://www.science.org/content/blog-post/gene-therapy-duchenne https://www.science.org/content/blog-post/gene-therapy-duche... ("Gene Therapy for Duchenne" (2018)) https://www.science.org/content/blog-post/opening-lid-sarepta-s-drug-approvals https://www.science.org/content/blog-post/opening-lid-sarept... ("Opening the Lid on Sarepta's Drug Approvals" (2020)) https://www.science.org/content/blog-post/sarepta-tries-again https://www.science.org/content/blog-post/sarepta-tries-agai... ("Sarepta Tries Again" (2023)) https://www.science.org/content/blog-post/sarepta-why https://www.science.org/content/blog-post/sarepta-why ("Sarepta. Why?" (2024))
- snitty 1y agoI've been working on a piece about how humans effectively have hardened firmware, and gene therapies need to do A LOT to try to get around the various defenses our bodies evolved. I should probably finish that article...
- mattigames 1y agoIf the institutions of science and technology lasted thousands of years evolution would prefer people with the less hardened firmware, as in, the ones to survive and pass their genes would be the ones with the most "hackable" genes.
- barbazoo 1y agoAre we still talking egg and sperm in a human body and everybody consenting? In that case, how would having hackable genes improve your chances of survival? If that was a dating app filter maybe.
- hamandcheese 1y agoIf your body doesn't reject gene therapy, you might live longer and reproduce more.
- barbazoo 1y agoI can see that now, thank you.
- catlikesshrimp 1y agoImagine all humans have homogeneous advantageous genetic material. We are all healthy and handsome. And then something random targets one or more of such advantageous genes and we are all wiped because we are very homogeneous. That happens to anything recombinant we produce: crops, cattle, bacteria. That even applies to dog breeds. "Advantageous" changes as the environment changes. Being a large long lived strong dinosaur is advantageous until meteorite? Then being a small mammal is advantageous. A population explosion of locusts ravages all plants successfully, until a fungus infects and kills almost all, thankfully for locusts some of them which were not "the best" survived that one infection.
- gary_0 1y agoApparently the treatment costs $3.2 million. https://en.wikipedia.org/wiki/Delandistrogene_moxeparvovec https://en.wikipedia.org/wiki/Delandistrogene_moxeparvovec
- scoot 1y agoThat seems very expensive for assisted suicide
- ricardobeat 1y agoWhy does the Wikipedia page treat this as a publicly available treatment when it is still undergoing trials?
- ygjb 1y agoProbably because of this: Delandistrogene moxeparvovec was approved for medical use in the United States in June 2023.[3][7] It was developed by Sarepta Therapeutics, together with Roche, and is manufactured by Catalent.[8]
- refurb 1y agoIt's not the same drug for the latest death this article is focused on... "Phase I study of SRP-9004".
- csours 1y agoWhatever policy we pursue, whatever decision we make, is not forever (at a society level). When people die, we change policy. When people feel like they cannot get the treatment they need, we change policy. Unfortunately, this is very complicated and emotionally heavy, and it is much easier to set down the burden on someone else's shoulders, in the form of blame. We want the FDA to do life critical, complicated and contradictory things, so it's easy to create a narrative that blames the FDA. The other option besides blame is shared responsibility and humility, but it feels like people are not very good at thinking that way right now.
- feoren 1y agoNobody "created" a narrative that blames the FDA. The FDA is factually complicit in these deaths. Three review teams and two senior officials voted unanimously against approval, but the (then) head of FDA's CBER was buddies with Sarepta, and so they got approved and three people have died. Nobody created that narrative. It's simply what happened.
- BrittneyCarven 1y ago[dead]