7 ms·

Sarepta. Why?

98 points by rossdavidh 2y ago

rossdavidh 2y ago
"The agency has just granted that use expansion, and it turns out that it was all due to Peter Marks, who completely overruled three review teams and two of his highest-level staffers (all of whom said that Sarepta had not proven its case)."
- abirch 2y ago
  It's sad when drugs are sold on hope and not on science. This reminds me of Biogen's Alzheimer's drug that eventually was stopped after millions were spent by people hoping it would work with controversial clinical results: https://www.politico.com/news/2024/01/31/biogen-alzheimers-drug-00138761 https://www.politico.com/news/2024/01/31/biogen-alzheimers-d...
greenavocado 2y ago
[flagged]
- _uhtu 2y ago
  Except the COVID vaccines passed clinical trials with flying colors. I believe not a single person from any of the Pfizer or Moderna trials died of COVID (people with the vaccine did, later, die of COVID, but at much, much, MUCH, lower rates than the unvaccinated). That's genuinely insane levels of drug success. You make an okay point, that the FDA needs some reform, but don't try to turn this into an anti-vax conspiracy ground, focus on actual issues where actual questionable activity exists.
  - mohaine 2y ago
    At least for the Pfizer study, no Covid-19–associated deaths were observed in the study or control groups so this says more about COVID and the study than about the vaccine itself. https://www.nejm.org/doi/full/10.1056/NEJMoa2034577 https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
    - jjoonathan 2y ago
      They were able to assess the efficacy by looking for illness, not death. It takes some verrrry "special" framing to twist this into anything but an enormous success: > BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Yet the deaths clearly mattered when multiplied up to population scale, because COVID was able to fill up the hospitals.
  - blackeyeblitzar 2y ago
    Didn’t these companies ask for and get immunity from liability relating to these vaccines? What do you make of that? Also are these products really correctly labeled as vaccines given their protection is imperfect and not like actual vaccines? I wonder if some other term is more accurate and would eliminate some of the arguments around them.
    - jjoonathan 2y ago
      > given their protection is imperfect and not like actual vaccines Since when were "actual vaccines" anywhere near perfect? The COVID vaccines were unusually good for vaccines, not unusually bad. Even a low-efficacy vaccine can still be high-efficacy in a population due to herd immunity (you don't need 100% protection, you just need to push R below 1.0 so that the infected subpopulation sees exponential decay rather than exponential growth), but we don't even need to consider this nuance in the case of the COVID vaccines because they surprised so strongly to the upside.
    - tlb 2y ago
      Why wouldn't you ask for liability protection? No matter how safe, like even if the injection was actually pure water, thousands of people would be convinced they were injured and sue for millions which, even if you won every case, costs a fortune in legal fees. No vaccine is perfect. They work by showing your immune system some example germ features, and most people's immune systems learn to defend against them. But immune systems are extremely complex and variable between people, and you can never guarantee a particular response. Vaccines sometimes completely eliminate some diseases (smallpox is one). They do this not by giving every person 100% protection individually, but by reducing transmission enough that the germ dies out.
  - HypnoDrone 2y ago
    Didn't they all die of pneumonia or some other such hand-wavey explanation so as to not outright blame covid?
  - amluto 2y ago
    > That's genuinely insane levels of drug success. The trials did indeed look pretty good, and they met their primary endpoints, but they were necessarily short-term trials, and IMO they were nowhere near as impressive as some of the old impressive vaccines. Try reading up on the history of the varicella vaccine: https://academic.oup.com/jid/article/226/Supplement_4/S375/6764810?login=false https://academic.oup.com/jid/article/226/Supplement_4/S375/6... Apparently you can give the vaccine after exposure, and it’s nearly 100% effective. 50 years after development and ~30 years after widespread rollout began in the US, the same vaccine still works, although the number of doses given has been increased to two because a single dose wasn’t quite good enough for herd immunity. (Chickenpox is far more contagious than at least the original COVID strain was.) I rate the COVID vaccines as an excellent improvement for society, absolutely worth getting in most populations and unquestionably worthy of approval, but merely so-so on the scale of vaccines. (I’m not sure I rate them worthy of continued approval and widespread deployment at current prices. If nothing else, serious follow up should be required to determine how repeated use of the mRNA vaccines compares to, say, Novavax. And health agencies should consider moving to a fee-for-efficacy model instead of a we-pay-whatever model — if pharma companies know, in advance, that they’ll get paid more for doses of a better vaccine, maybe they’ll make one instead of resting on their mediocre laurels.)
    - jjoonathan 2y ago
      That's like calling Arnold Schwarzenegger a weakling because Hafþór Júlíus Björnsson was stronger.
    - pama 2y ago
      You compare apples and oranges. These are completely different viruses. There are pills like aspirin that dont help against cancer either.. and we still dont have a vaccine against SARS-1 or MERS.
  - deleted 2y ago
    [deleted]
- ToucanLoucan 2y ago
  > People lost their jobs over the refusals. A lot of those people lost a lot more than their jobs in the end.
- jjoonathan 2y ago
  The vaccines were so good at their job that the hospitals were full of unvaccinated people even after most people got vaccinated, and this astonishing feat of efficacy persisted for quite some time. Normally I'm sympathetic to a bit of healthy cynicism, but when the official narrative is backed by extremely strong extremely public corroborating evidence, sorry, I'm not going to sacrifice the safety of myself and those I care about to indulge someone else's politically-driven blindness towards said evidence.
  - RIMR 2y ago
    There is a disturbing trend on the right to reject literally anything a state org says as if it were some sort of brave rebellion against the system. The CDC says wear masks? Suddenly it becomes a "mind control" issue. The FDA recommends not drinking raw milk? Republican lawmakers are literally sickening themselves drinking bacteria-laden dairy products in front of their colleagues to "trigger the libs". The FDA issue emergency authorization to get a COVID vaccine to the public as quickly as possible during a pandemic, and suddenly Conservatives are claiming that COVID never killed anyone, it's the Vaccine that's killing people, even as the unvaccinated make up the lion's share of the casualties. If you dive deep enough into the antivaxxer movements (a deeply right-wing movement), you'll find people arguing that drinking industrial bleach (Miracle Mineral Cure) is the solution to every health issue that "they don't want you to know about", even as they are shitting out pieces of their intestines (Google "rope worms"). Of courset the government saying "don't drink bleach" makes them double down. I am all for a healthy distrust of the government or any other ruling authority, but it feels like roughly half the the U.S. population is so brain-broken that they have fully embraced contrarianism as a worldview.
- RIMR 2y ago
  >Experimental COVID vaccines They were never experimental. At this point in the game, if you're still repeating this lie, you're just revealing how little you understand about the world around you due to how much propaganda you believe. And yes, refusing to do what your employer requires of you for the job will get you fired. Welcome to the free market. For decades employers have made vaccines for many different diseases a requirement of employment. You have the freedom not to get vaccinated, and your employer has the right to show you the door.
  - blackeyeblitzar 2y ago
    > You have the freedom not to get vaccinated, and your employer has the right to show you the door. They really shouldn’t have that right. It’s discriminatory and a violation of basic rights to bodily autonomy. No one should be forced to undergo a medical procedure for employment. Others who may be worried about some illness are free to manage their own risk by wearing protection instead of forcing such choices on others.
    - jjoonathan 2y ago
      [flagged]
    - taylodl 2y ago
      [flagged]
  - hggh 2y ago
    > They were never experimental Most of them have an emergency authorization, not full [0], so pretty much experimental. [0] https://en.wikipedia.org/wiki/List_of_COVID-19_vaccine_authorizations https://en.wikipedia.org/wiki/List_of_COVID-19_vaccine_autho...
    - RIMR 2y ago
      Look, literally nobody in the medical community considers it experimental. If you want to believe that you were being experimented on by getting vaccinated, you are free to believe whatever you want, but you are 100% factually wrong and most everyone around you knows it.
- m3kw9 2y ago
  You trust vaccines which doctors recommend, just like all medical advise your doctors recommend. Otherwise you maybe a few that never goes to a doc because you never trust anything they say. Healthy skepticism is good but ultimately you go to them because they have a track record of saving people
derlvative 2y ago
Picture the situation: someone you love has just been diagnosed with a death sentence disease with no know treatment. The FDA just chose not to outlaw a promising but unproven new treatment for it. Now you get to choose whether to take it or not. And somehow the FDA are evil twisted bad guys!?
- jostmey 2y ago
  Except that the FDA frequently denies treatments lacking evidence of benefit except in these two cases. The real problem is that it costs too much to bring new treatments through a clinical trial
  - derlvative 2y ago
    Except that I don't think the FDA should do that? I'm arguing that people should have options that are not certain death.
    - hmottestad 2y ago
      Not much point researching a better treatment when you can just sell something that doesn't work.
    - cool_dude85 2y ago
      Here's an option: buy cool dude tincture at 10 dollars a bottle instead of this treatment at 10 thousand or whatever.
  - Aurornis 2y ago
    The point was that people are up in arms about either outcome: FDA denies approval, people get angry. FDA allows approval, people get angry. > The real problem is that it costs too much to bring new treatments through a clinical trial As opposed to what? Just letting anything go? We basically have that situation in the alternative medicine world and the grifters are out in full force peddling things that we know don’t work the way they claim. Imagine how bad it would be if we waived away clinical trial requirements.
kickaha 2y ago
Often it pays simply to remember what a rigidly ideological culture we inhabit. Imagine it's 1986 and this story comes from SoViEt RuSsIa. Derek Lowe (who I hold to be adjacent to a National Treasure) would not be obliged to speculate about motives. The entire bloviosphere would unanimously collapse into mockery. The word is "corrupt." It's simple.
- deleted 2y ago
  [deleted]
haunter 2y ago
[flagged]
- kibwen 2y ago
  At some point we need to have a talk about the "no editorialized titles" rule, because while I agree that there's a risk of having the submitter inject their own bias, a title of "Sarepta. Why?" is totally beyond useless for a news aggregator website that isn't exclusively tailored for pharma. I propose two fields when submitting a link: the original title, and an optional "additional context" field.
  - jlund-molfese 2y ago
    I agree, there's a pretty big difference between editing a title to remove clickbait/excessive slant and editorializing an already-descriptive title to apply a bias.
- tomashubelbauer 2y ago
  That's a shit title. I am not sure the HN submission is a better title, but this is the kind of post where I think the title should definitely be editorialized to give a hint of what the post is actually about and some context.
- cool_dude85 2y ago
  You're right, the article only refers to "review teams", surely quite different from a "review board".
emagdnim2100 2y ago
Well, it’s a good start anyway.
deleted 2y ago
[deleted]
w10-1 2y ago
Approved with 40% experiencing liver injury? Check out the statistical evaluation sections on the study outcomes: https://www.fda.gov/vaccines-blood-biologics/tissue-tissue-products/elevidys I could see approval override when evidence is marginally positive but impossible to improve (e.g., for lack of study subjects - here ~150 with a rare genetic disease) when the benefit is clear and there is no safety risk (adverse effects - AE). The primary outcome didn't fail by much in the small sample. It's an assessment scale of physical activity which can be hard to get right and perhaps prone to false negatives for slow responders. So, maybe. But the liver injury (lots of bad labs) is a significant side effect, as is nausea/vomiting (~50%), fever (~30%), and thrombocytopenia (8%). Even with that, there was no discontinuation d/t AE, because the patients (parents) are so motivated. I'd like to see how quickly patients recovered esp. to normal liver labs, and also understand how whether other gene therapies have shown similar reactions to be transient and benign. There's probably a lot of variability in immune systems at that age, with possible long-term effects from adverse training. The variability could result in severe problems in a few cases, and the adverse immune training could result in lifelong auto-immune diseases, etc. Which means there's reason for caution. As for corruption... Fatalism about corruption is exactly what corrupt regimes nurture, because it passivates objectors and activates collaborators. Please let's not go there. The FDA process situation now is OK: both staff and advisors are on the record, so any inconsistent top-line decision is clearly discoverable. As far as I can tell, staff and advisory board selection is mostly per scientific skill, albeit with industry representation, and also on the record so that influence can be traced. Above all, reasons are justified and traced to studies on the record, and most marginal approvals (like this one) include post-marketing monitoring to claw back the approval as needed. (My primary objection now is that study data is mostly non-public, and AFAICT there's no requirement to publish negative data).

98 points by rossdavidh 2y ago

"The agency has just granted that use expansion, and it turns out that it was all due to Peter Marks, who completely overruled three review teams and two of his highest-level staffers (all of whom said that Sarepta had not proven its case)."

abirch 2y ago
It's sad when drugs are sold on hope and not on science. This reminds me of Biogen's Alzheimer's drug that eventually was stopped after millions were spent by people hoping it would work with controversial clinical results: https://www.politico.com/news/2024/01/31/biogen-alzheimers-drug-00138761 https://www.politico.com/news/2024/01/31/biogen-alzheimers-d...

greenavocado 2y ago

[flagged]

_uhtu 2y ago
Except the COVID vaccines passed clinical trials with flying colors. I believe not a single person from any of the Pfizer or Moderna trials died of COVID (people with the vaccine did, later, die of COVID, but at much, much, MUCH, lower rates than the unvaccinated). That's genuinely insane levels of drug success. You make an okay point, that the FDA needs some reform, but don't try to turn this into an anti-vax conspiracy ground, focus on actual issues where actual questionable activity exists.
- mohaine 2y ago
  At least for the Pfizer study, no Covid-19–associated deaths were observed in the study or control groups so this says more about COVID and the study than about the vaccine itself. https://www.nejm.org/doi/full/10.1056/NEJMoa2034577 https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
  - jjoonathan 2y ago
    They were able to assess the efficacy by looking for illness, not death. It takes some verrrry "special" framing to twist this into anything but an enormous success: > BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Yet the deaths clearly mattered when multiplied up to population scale, because COVID was able to fill up the hospitals.
- blackeyeblitzar 2y ago
  Didn’t these companies ask for and get immunity from liability relating to these vaccines? What do you make of that? Also are these products really correctly labeled as vaccines given their protection is imperfect and not like actual vaccines? I wonder if some other term is more accurate and would eliminate some of the arguments around them.
  - jjoonathan 2y ago
    > given their protection is imperfect and not like actual vaccines Since when were "actual vaccines" anywhere near perfect? The COVID vaccines were unusually good for vaccines, not unusually bad. Even a low-efficacy vaccine can still be high-efficacy in a population due to herd immunity (you don't need 100% protection, you just need to push R below 1.0 so that the infected subpopulation sees exponential decay rather than exponential growth), but we don't even need to consider this nuance in the case of the COVID vaccines because they surprised so strongly to the upside.
  - tlb 2y ago
    Why wouldn't you ask for liability protection? No matter how safe, like even if the injection was actually pure water, thousands of people would be convinced they were injured and sue for millions which, even if you won every case, costs a fortune in legal fees. No vaccine is perfect. They work by showing your immune system some example germ features, and most people's immune systems learn to defend against them. But immune systems are extremely complex and variable between people, and you can never guarantee a particular response. Vaccines sometimes completely eliminate some diseases (smallpox is one). They do this not by giving every person 100% protection individually, but by reducing transmission enough that the germ dies out.
- HypnoDrone 2y ago
  Didn't they all die of pneumonia or some other such hand-wavey explanation so as to not outright blame covid?
- amluto 2y ago
  > That's genuinely insane levels of drug success. The trials did indeed look pretty good, and they met their primary endpoints, but they were necessarily short-term trials, and IMO they were nowhere near as impressive as some of the old impressive vaccines. Try reading up on the history of the varicella vaccine: https://academic.oup.com/jid/article/226/Supplement_4/S375/6764810?login=false https://academic.oup.com/jid/article/226/Supplement_4/S375/6... Apparently you can give the vaccine after exposure, and it’s nearly 100% effective. 50 years after development and ~30 years after widespread rollout began in the US, the same vaccine still works, although the number of doses given has been increased to two because a single dose wasn’t quite good enough for herd immunity. (Chickenpox is far more contagious than at least the original COVID strain was.) I rate the COVID vaccines as an excellent improvement for society, absolutely worth getting in most populations and unquestionably worthy of approval, but merely so-so on the scale of vaccines. (I’m not sure I rate them worthy of continued approval and widespread deployment at current prices. If nothing else, serious follow up should be required to determine how repeated use of the mRNA vaccines compares to, say, Novavax. And health agencies should consider moving to a fee-for-efficacy model instead of a we-pay-whatever model — if pharma companies know, in advance, that they’ll get paid more for doses of a better vaccine, maybe they’ll make one instead of resting on their mediocre laurels.)
  - jjoonathan 2y ago
    That's like calling Arnold Schwarzenegger a weakling because Hafþór Júlíus Björnsson was stronger.
  - pama 2y ago
    You compare apples and oranges. These are completely different viruses. There are pills like aspirin that dont help against cancer either.. and we still dont have a vaccine against SARS-1 or MERS.
- deleted 2y ago
  [deleted]
ToucanLoucan 2y ago
> People lost their jobs over the refusals. A lot of those people lost a lot more than their jobs in the end.
jjoonathan 2y ago
The vaccines were so good at their job that the hospitals were full of unvaccinated people even after most people got vaccinated, and this astonishing feat of efficacy persisted for quite some time. Normally I'm sympathetic to a bit of healthy cynicism, but when the official narrative is backed by extremely strong extremely public corroborating evidence, sorry, I'm not going to sacrifice the safety of myself and those I care about to indulge someone else's politically-driven blindness towards said evidence.
- RIMR 2y ago
  There is a disturbing trend on the right to reject literally anything a state org says as if it were some sort of brave rebellion against the system. The CDC says wear masks? Suddenly it becomes a "mind control" issue. The FDA recommends not drinking raw milk? Republican lawmakers are literally sickening themselves drinking bacteria-laden dairy products in front of their colleagues to "trigger the libs". The FDA issue emergency authorization to get a COVID vaccine to the public as quickly as possible during a pandemic, and suddenly Conservatives are claiming that COVID never killed anyone, it's the Vaccine that's killing people, even as the unvaccinated make up the lion's share of the casualties. If you dive deep enough into the antivaxxer movements (a deeply right-wing movement), you'll find people arguing that drinking industrial bleach (Miracle Mineral Cure) is the solution to every health issue that "they don't want you to know about", even as they are shitting out pieces of their intestines (Google "rope worms"). Of courset the government saying "don't drink bleach" makes them double down. I am all for a healthy distrust of the government or any other ruling authority, but it feels like roughly half the the U.S. population is so brain-broken that they have fully embraced contrarianism as a worldview.
RIMR 2y ago
>Experimental COVID vaccines They were never experimental. At this point in the game, if you're still repeating this lie, you're just revealing how little you understand about the world around you due to how much propaganda you believe. And yes, refusing to do what your employer requires of you for the job will get you fired. Welcome to the free market. For decades employers have made vaccines for many different diseases a requirement of employment. You have the freedom not to get vaccinated, and your employer has the right to show you the door.
- blackeyeblitzar 2y ago
  > You have the freedom not to get vaccinated, and your employer has the right to show you the door. They really shouldn’t have that right. It’s discriminatory and a violation of basic rights to bodily autonomy. No one should be forced to undergo a medical procedure for employment. Others who may be worried about some illness are free to manage their own risk by wearing protection instead of forcing such choices on others.
  - jjoonathan 2y ago
    [flagged]
  - taylodl 2y ago
    [flagged]
- hggh 2y ago
  > They were never experimental Most of them have an emergency authorization, not full [0], so pretty much experimental. [0] https://en.wikipedia.org/wiki/List_of_COVID-19_vaccine_authorizations https://en.wikipedia.org/wiki/List_of_COVID-19_vaccine_autho...
  - RIMR 2y ago
    Look, literally nobody in the medical community considers it experimental. If you want to believe that you were being experimented on by getting vaccinated, you are free to believe whatever you want, but you are 100% factually wrong and most everyone around you knows it.
m3kw9 2y ago
You trust vaccines which doctors recommend, just like all medical advise your doctors recommend. Otherwise you maybe a few that never goes to a doc because you never trust anything they say. Healthy skepticism is good but ultimately you go to them because they have a track record of saving people

derlvative 2y ago

Picture the situation: someone you love has just been diagnosed with a death sentence disease with no know treatment. The FDA just chose not to outlaw a promising but unproven new treatment for it. Now you get to choose whether to take it or not. And somehow the FDA are evil twisted bad guys!?

jostmey 2y ago
Except that the FDA frequently denies treatments lacking evidence of benefit except in these two cases. The real problem is that it costs too much to bring new treatments through a clinical trial
- derlvative 2y ago
  Except that I don't think the FDA should do that? I'm arguing that people should have options that are not certain death.
  - hmottestad 2y ago
    Not much point researching a better treatment when you can just sell something that doesn't work.
  - cool_dude85 2y ago
    Here's an option: buy cool dude tincture at 10 dollars a bottle instead of this treatment at 10 thousand or whatever.
- Aurornis 2y ago
  The point was that people are up in arms about either outcome: FDA denies approval, people get angry. FDA allows approval, people get angry. > The real problem is that it costs too much to bring new treatments through a clinical trial As opposed to what? Just letting anything go? We basically have that situation in the alternative medicine world and the grifters are out in full force peddling things that we know don’t work the way they claim. Imagine how bad it would be if we waived away clinical trial requirements.

kickaha 2y ago

Often it pays simply to remember what a rigidly ideological culture we inhabit. Imagine it's 1986 and this story comes from SoViEt RuSsIa. Derek Lowe (who I hold to be adjacent to a National Treasure) would not be obliged to speculate about motives. The entire bloviosphere would unanimously collapse into mockery. The word is "corrupt." It's simple.

deleted 2y ago
[deleted]

haunter 2y ago

[flagged]

kibwen 2y ago
At some point we need to have a talk about the "no editorialized titles" rule, because while I agree that there's a risk of having the submitter inject their own bias, a title of "Sarepta. Why?" is totally beyond useless for a news aggregator website that isn't exclusively tailored for pharma. I propose two fields when submitting a link: the original title, and an optional "additional context" field.
- jlund-molfese 2y ago
  I agree, there's a pretty big difference between editing a title to remove clickbait/excessive slant and editorializing an already-descriptive title to apply a bias.
tomashubelbauer 2y ago
That's a shit title. I am not sure the HN submission is a better title, but this is the kind of post where I think the title should definitely be editorialized to give a hint of what the post is actually about and some context.
cool_dude85 2y ago
You're right, the article only refers to "review teams", surely quite different from a "review board".

emagdnim2100 2y ago

Well, it’s a good start anyway.

deleted 2y ago

[deleted]

w10-1 2y ago

Approved with 40% experiencing liver injury? Check out the statistical evaluation sections on the study outcomes: https://www.fda.gov/vaccines-blood-biologics/tissue-tissue-products/elevidys I could see approval override when evidence is marginally positive but impossible to improve (e.g., for lack of study subjects - here ~150 with a rare genetic disease) when the benefit is clear and there is no safety risk (adverse effects - AE). The primary outcome didn't fail by much in the small sample. It's an assessment scale of physical activity which can be hard to get right and perhaps prone to false negatives for slow responders. So, maybe. But the liver injury (lots of bad labs) is a significant side effect, as is nausea/vomiting (~50%), fever (~30%), and thrombocytopenia (8%). Even with that, there was no discontinuation d/t AE, because the patients (parents) are so motivated. I'd like to see how quickly patients recovered esp. to normal liver labs, and also understand how whether other gene therapies have shown similar reactions to be transient and benign. There's probably a lot of variability in immune systems at that age, with possible long-term effects from adverse training. The variability could result in severe problems in a few cases, and the adverse immune training could result in lifelong auto-immune diseases, etc. Which means there's reason for caution. As for corruption... Fatalism about corruption is exactly what corrupt regimes nurture, because it passivates objectors and activates collaborators. Please let's not go there. The FDA process situation now is OK: both staff and advisors are on the record, so any inconsistent top-line decision is clearly discoverable. As far as I can tell, staff and advisory board selection is mostly per scientific skill, albeit with industry representation, and also on the record so that influence can be traced. Above all, reasons are justified and traced to studies on the record, and most marginal approvals (like this one) include post-marketing monitoring to claw back the approval as needed. (My primary objection now is that study data is mostly non-public, and AFAICT there's no requirement to publish negative data).