15 ms·

An ALS drug fails, again

137 points by kurthr 3y ago

kurthr 3y ago
This drug was approved after Phase II trials largely failed and a second review panel was convened to override the first. Now it has failed again in Phase III after being given to many hopeful patients at great cost. The last lines rang true: You need what you've always needed: efficacy and safety. Boring, tedious, expensive efficacy and safety. Desire and despair don't figure in much - in a much different universe, one whose physical laws respected and validated human emotions and human suffering, they would. But we don't live in that world.
- deleted 3y ago
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- echelon 3y ago
  [flagged]
  - jobs_throwaway 3y ago
    On an individual level that's rational, but on an institutional level the safeguards and caution are also rational. If you are able to make the drugs/experiments yourself, knock yourself out. But don't expect huge corporations/governments to do it for you
    - tiahura 3y ago
      Shouldn't the safeguards be inversely proportional to the level of untreatable misery?
      - JumpCrisscross 3y ago
        > Shouldn't the safeguards be inversely proportional to the level of untreatable misery? This is tautology’s Treatment is the variable. What constitutes the untreatable is the point of the question.
    - aeternum 3y ago
      The safeguards and caution are even more immoral from a rationalist point of view. By delaying potential medical breakthroughs you cause many future humans some amount of additional suffering because medical breakthroughs build on one another. If you delay an ALS cure by one year, you are not only harming all those who have ALS for that year but all those present and future humans that have other diseases that could benefit from the future research tree branching out from that ALS cure. Suppose for example that our ancestors were more risk-averse, more focused on the moral "do no harm" and thereby agreed upon 20 year trials for all new surgical procedures. What would 'modern' surgery look like? We should be celebrating the risk-takers as willingness to take an experimental drug or an experimental treatment as it is often a greater gift to humanity than an organ donation.
  - thenerdhead 3y ago
    https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190...
    - echelon 3y ago
      This is exactly the right direction.
  - caslon 3y ago
    There are other countries, ones where it's legal to do medical experimentation upon any consenting party. Unsurprisingly, they don't create significant amounts of novel drugs. Why? Because the US system is more profitable, and, similar to how writing proprietary software is the most common way to earn a living as a software engineer, people like money. Similar to platforms that claim to "democratize" a given hobby while at the end of the day being proprietary SaaS, people can claim as good of motives as they want, but at the end of the day, they want to make enough money to sit on their heels. The government strongly incentivizes drugs that are economically worthless without it. The US system ensures that everyone gets paid. Laissez-faire drug development wouldn't. As better in theory as it may be, just like free software, in practice, you'd probably get fewer returns than the controlled system, just because people aren't altruistic, and nobody cares about niche diseases that doesn't have direct motive.
    - echelon 3y ago
      Not once did I propose changing the economic model. Only that we should give consenting, perhaps eager, terminal patients more options in participating in research and access to promising new drugs. It's unfair that there's a decade of waiting when lives are so quickly and pointlessly lost. You're alive as a conscious participant in the universe just once, and then there's an infinity of nothing. You should have the option to try to keep that spark alive. If a chance, even fleeting, lies behind a glass door, that's cruel.
      - catlikesshrimp 3y ago
        If you did that, there would be a rush of (not necessarily) terminal patients signing up and mostly dieing anyways (hopefully of their terminal illnesses) There would be, as expected, a large contingent of patients who were poor, alone and maybe not very terminal. The very same reason which lead to the creation of ethics committes
  - andrewflnr 3y ago
    Sometimes when you get a random stupid downvote, someone else will come along and fix it. I've been on both sides of that. But when you complain about it, that's pretty near a guarantee that I won't touch it. Because the point of downvotes is to suppress useless content, and complaining about how you're being "silenced" because someone downvoted you on a web forum definitely qualifies. You're not entitled to be heard. A forum is a shared space, so it doesn't work unless we all have a vote on what happens here. If you somehow create the universe where people have "complete control", and you say annoying or even boring stuff, you won't get downvoted, you'll just get blackholed. Do you think that'll feel better? Anyway, don't take downvotes so seriously. Some days the hive is just cranky.
    - sillysaurusx 3y ago
      More to the point, I was going to vouch the comment (which removes the flagged status) till I got to the edits. It’s not possible to vouch it in its current state, because at best I’d be making a mistake, and at worst I’d lose my vouch privileges. So you’re literally making it impossible to salvage your comment when you go off on rants about censorship. There are thoughtful ways to comment about the moderation. If you take the time to phrase things in a substantive non-emotional way, and ask yourself "what am I trying to communicate?" you often end up with something that won’t be flagged. But the combination of user flags and manual mod review with the vouch system adding even more variability means that it’s a tossup whether any given decision will be reversed (or even can be reversed, since e.g. this one can’t be). It’s best to think of it like a casino and not worry on the days the cards don’t favor you. Amusingly, the change to rank flagged comments above downvoted comments in an effort to push them to places less-seen has catapulted this subthread to the second top comment of the whole submission, which I haven’t seen before. HN never fails to surprise.
      - andrewflnr 3y ago
        Interesting. It wasn't flagged when I commented. So it got flagged, vouched, and flagged again? I hadn't heard of/seen that ordering change. Also interesting. Though I can't agree with your last line, HN is very predictable sometimes. For instance, any thread about dark matter is reliably a mess. :D
  - deleted 3y ago
    [deleted]
- thenerdhead 3y ago
  How about we fix that with this? https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190... Give patients access and do the right science. Make sure it is safe and allow people the right to try.
  - capitainenemo 3y ago
    In the case of the parent article drug, it claims it was the pressure of patient advocacy groups that got the drug approved. Giving people the right to try unfortunately at present means everyone else paying for it (or paying for the harm it causes), unless unapproved drugs were required to be covered by the individual on their own. " But ALS patients (or their insurance companies) had the chance to pay for a drug ($158,000/yr list, who knows what the real price was somewhere below that) for what is in the end a combination of two generic medicines. And they might as well have been given peppermint candy for all the good it did. ... patient advocacy groups took victory laps after Relyvrio was approved, and they were a big part of the pressure that made the FDA reverse its initial correct decision "
  - peeters 3y ago
    Can you expand on this? This bill seems to enable exactly what the author is attacking: exploiting the desperate hopes of terminally ill patients to sell ineffective drugs. I agree with removing red tape and allowing accelerated trials when the drugs are for these purposes, but it seems like today, drug companies can make a profit off of selling snake oil. They already stand to benefit from the reduced regulations, so why allow them to sell the drug at all under these circumstances? If they're so confident in the efficacy, they should be willing to give the drug away for free to benefit from an accelerated path to approval. This bill seems to allow drug companies to continue to sell under these regulations, and in fact goes even further by removing most liability from them.
    - yieldcrv 3y ago
      > but it seems like today, drug companies can make a profit off of selling snake oil anybody can sell sugar pills or any 'generally approved as safe' consumptive good, repackaged as something big pharma is hiding from you
deleted 3y ago
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msie 3y ago
It's crazy how this drug got approved despite the evidence. A mixture of greed from the drug manufacturer and wishful thinking from the afflicted. Ugh. I've lost my trust in the system.
- frodo8sam 3y ago
  Agree, the Alzheimer's and ALS treatments that were approved recently were both cases where the patient advocacy groups stopped listening to experts and ironically harmed the people they are trying to help. It shows how important it is that the FDA keeps some emotional distance from the people they are trying to protect.
  - ta8645 3y ago
    That's an interesting narrative, but are you sure that's actually what happened? It seems to elide the role of the drug manufacturer who pays for all these trials in the first place. Why would they pay for such doomed trials, just for the emotional hopes of patients? Are they that irresponsible with their stockholder's money? If so, they should probably be ousted and replaced with people who have more business savvy. Or alternatively, this really didn't have anything to do with hopeful patients or their advocates, but rather the greed of the pharma companies, hoping to push through unproven drugs for the sake of profit. I don't have any special insight into which narrative is true, but we've seen a lot of the second narrative historically.
    - jfengel 3y ago
      They can't profit if it doesn't work. There is that bizarre case with the Alzheimer's drug, but that seems rare and not something they should pin their hopes on. It sounds to me as if the drugmakers and the patient advocates are coming from the same place. They are desperate for it to work, and will convince themselves of it on any thin evidence. Probably something like "it did X in a petri dish so it must work eventually." There are surely executives making a calculated risk, but I think they couldn't do it if there weren't also scientists who feed them over-optimistic guesses because they want it to work for the patients too.
light_hue_1 3y ago
We sometimes have posts here from patients who are desperate. And everyone dumps on the FDA in those threads. This is the flip side of that. This was patients lobbying Congress to skip safeguards. The FDA did not want to do this. https://apnews.com/article/science-business-health-lobbying-congress-08f90cb109edd90fd7dd94d608960a05 https://apnews.com/article/science-business-health-lobbying-... Now it's just getting worse and worse. ALS patient communities used the questionable approval of Aduhelm by desperate Alzheimer’s patients to strongarm the FDA into approving this. Every junk pharma product is now going to come with an advocacy group that says "let's just try it and see". Grifter pharma corporations will of course take advantage of this. They'll mobilize patient communities to keep skipping the science. And the result will be more wasted lives and more misallocated resources. Instead of working toward drugs that help people, we'll be working toward drugs that sound good to patient communities and Congress. This is a disaster. The FDA might be slow. But it's slow and deliberate for a reason.
- rafaelero 3y ago
  But what's the harm here? The drug is safe. The only burden patients had was financial. Now what if the drug was effective? The harm it would incur to patients by delaying it would be much more extreme.
  - ejb999 3y ago
    the harm is not all drugs are safe - even if this one was (and we aren't 100% sure of that either), and pharma companies using social media and/or sympathy stories to pressure regulators into approving a drug that would not otherwise get approved is gross.
    - rafaelero 3y ago
      That's what Phase II is for.
  - SoftTalker 3y ago
    Even if it's safe, the harm is in rewarding drug companies for producing very expensive products that don't work, and selling them to desperate people and their families who will sell off everything they own and go as far into debt as they can to pay for them. This creates incentives that we don't or should not want.
optimalsolver 3y ago
[flagged]
- azinman2 3y ago
  What would you rather have in this scenario? Earlier phases almost certainly started on animal models. How do you know it will or won’t work in humans if you don’t do clinical trials? Keep in mind 90% of drugs fail clinical trials, and that’s almost certainly after showing success in animal models.
dddddaviddddd 3y ago
> The Phase III trial has just read out, and Relyvrio shows no hint of actually working.... It did have a very good safety profile, fortunately, so it seems unlikely that anyone was physically harmed. Phase II trials are more about safety than efficacy, so I'd say the system worked as designed.
- iechoz6H 3y ago
  One wonders how they got as far as Phase III trials without actually working.
  - zeroonetwothree 3y ago
    Phase III is when you test efficacy so it’s exactly how it’s meant to be
    - moritzwarhier 3y ago
      considering costs this doesn't sound very utilitarian
      - pc86 3y ago
        Why would you test something for efficacy before you're sure it's safe? You'll end up testing a bunch of harmful substances that don't actually do anything.
        moritzwarhier 3y ago
        Fair point, although it also seems nonsensical to test safety for human consumption before having a robust hypothesis for desired effects. It's not true that safety is fast and easy to check.
        SoftTalker 3y ago
        Maybe because the real standard is "the benefits out weigh the risks" you might want a drug that has a 10% chance of harm if it has a 90% chance of benefit, for a condition that is terminal if untreated.
dlevine 3y ago
There was a good article on this in the New Yorker a while back: https://www.newyorker.com/magazine/2023/06/26/relyvrio-als-fda-approval https://www.newyorker.com/magazine/2023/06/26/relyvrio-als-f... It's sad that the drug didn't work (and I had a cousin recently die of ALS), but it's important to let the FDA do their work.
- thenerdhead 3y ago
  What work does the FDA do here? It is the work of large investments or initiatives to prove safety and efficacy and the FDA makes decisions. If anything we live in a world where we need better provisions for these illnesses similar to https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190... Waiting for phased trials when you understand the research and hypothetical risks is torture. Especially when many drugs have proven safety profiles where the only harm is financial.
  - ProjectArcturis 3y ago
    This particular drug was just a combination of two already-approved generic drugs. Anyone could have tried them with a doctor's Rx without a change in the law.
    - thenerdhead 3y ago
      Ah so a patent company who wanted to make a profit? https://www.regulations.gov/docket/FDA-2023-E-2605 https://www.regulations.gov/docket/FDA-2023-E-2605 Interesting!
      - downvotetruth 3y ago
        Infuriating that government site does not even display without JavaScript.
- hash872 3y ago
  >but it's important to let the FDA do their work The FDA has been 'working' on authorizing sunscreen widely used in the rest of the developed world for the last 20 years, or since the original Dubya administration. This is not a typo. They are glacially, bureaucratically slow & cautious
cat_plus_plus 3y ago
Said no patient ever. Everyone wants right to try, understandable that insurance would only cover sufficiently proven treatments. But if I can raise money, I want to at least take the most promising currently and if it doesn't work, oh well.
- ryukoposting 3y ago
  I think the important detail here is that, to anyone paying attention to the results of the clinical trials, this drug never showed promise in the first place. The system we have is slow because it's thorough. Sometimes we have to move faster, and that's what EUAs are for. The worst versions of "right to try" policy would open the floodgates to all kinds of quack drugs with astronomical price tags. The resulting system would extract money from the desperate, and do very little to cure the ill.
  - thenerdhead 3y ago
    Not true. You can mark certain confirmed illnesses with provisions. Quacks won’t be allowed in such regulated environments. https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190...
    - marcinzm 3y ago
      > Quacks won’t be allowed in such regulated environments. Presumably, however, pharmaceutical companies striving to maximize shareholder value at all costs are allowed which is probably much worse in the end.
      - thenerdhead 3y ago
        Yes they are free to do that if their drugs work. That’s allowed in any capitalist market.
        marcinzm 3y ago
karaterobot 3y ago
> An uncharitable view would be that Amylyx ended up presenting the clinical package from the only angle that made it even possible to believe that the drug worked, and the FDA advisory committee ended up voting against approval... I hate to be this way, but I continue to believe that unmet medical need is not by itself enough reason to approve a drug. You need what you've always needed: efficacy and safety. Boring, tedious, expensive efficacy and safety. I can either take from this that he believes the FDA and Amylyx were engaged in irresponsible behavior letting it get this far, or that (thank God!) an ineffective drug will not be approved, and we should all be glad there is a rigorous testing process that worked again. I get the sense that he believes the former, but can't ethically say so.
- ProjectArcturis 3y ago
  It's both. The FDA erred in approving this ineffective drug based on weak P2 data.
j7ake 3y ago
Failing so late in the drug process can literally bankrupt a company.
- thenerdhead 3y ago
  As it should. That’s the risk they take. Either you have a well designed trial that shows your drug is effective or you don’t. What you don’t do is make lofty promises to vulnerable patients.
- StanAngeloff 3y ago
  Amylyx Stock Wipes Out Nearly All Of Its Value, Crashing 82%, After Pivotal ALS Drug Failure[0] [0]: https://finance.yahoo.com/m/b15fb91a-1e90-3259-844e-cfdb256344de/amylyx-stock-wipes-out-nearly.html https://finance.yahoo.com/m/b15fb91a-1e90-3259-844e-cfdb2563...
  - consp 3y ago
    Probably someone made money off it as according to the article this was the clear outcome.
sudosteph 3y ago
My Dad has ALS and has participated in a couple trials for different treatments. It's hard to say if any of them made a difference at all, and the justification behind some of these drugs seems extremely flimsy (one he was doing was for a drug that had some weak correlation during covid for slightly slower progression in one symptom), and the quality life impact of participating in that trial (having to fly to Boston, drug side effects, multiple lumbar punctures) leaves me frustrated that doctors recommend these at all. I feel like they're trading favors to get patients into studies with doctors they know, meanwhile, there are more promising ones that are being tested that he should be a candidate for, but the doctor won't even have a conversation about trying to get him in those trials. It leaves a bitter taste in my mouth. I hope something comes from all this, but right now I don't have a high view of the drug research and treatment process for this condition.
- lambdaba 3y ago
  I hope this is not inapropriate but I wanted to share this interview with a person using a high fat diet for ALS: https://youtu.be/GoF4GZ1NoBQ?si=Y-yEnquZsLXXb2po https://youtu.be/GoF4GZ1NoBQ?si=Y-yEnquZsLXXb2po Noting that ketogenic diets are already proven to improve outcomes in other neurodegenerative diseases.
randomgiy3142 3y ago
There are bigger things than a failed trial. There was a lot of money invested in this and when it was found to not be harmful there was a large push to show success. A lot of careers will be cut short because of this. There’s a lot of motivation to show something works. I was told to avoid research because of this kind of thing. There were a lot of highly paid people in a room that were not scientists but tasked with showing how much money could be made. That sounds evil but their intentions are good, that doesn’t help ALS people but there’s enough money put into this I wouldn’t be surprised if some progress is shown somewhere.
tibbydudeza 3y ago
ALS or as Americans call it Lou Gehrig disease is a high-profile disease because of the ice bucket challenge despite the low incidence (6 out of 100,000) compared to other diseases like coronary disease or some cancers. The disease is cruel, and it hits home for many of us as there are no mental deterioration like with dementia, Alzheimer's or FPD but you lose the ability to use your body and survival less than 3 years. I can see why the FDA and congress are desperate to be seen to do something.
katherinebhana7 3y ago
ALS is a cruel disease. My mum is 83 and had great difficulty speaking and swallowing much of anything. Food was getting trapped in her throat and blocking her air way was happening more often. she battled for each breath. The riluzole did very little to help her. The medical team did even less. Her decline was rapid and devastating. The psychological support from the medical centre was non-existent and if it were not for the sensitive care and attention of our primary physician, there she would have died. There has been little if any progress in finding a cure or reliable treatment. Acupuncture eased her anxiety a bit. this year our primary physician started her on Natural Herbs Centre ALS/MND Ayurvedic treatment, 6 months into treatment she improved dramatically. It has been a complete turnaround with her speech, she no longer needs the feeding tube to feed, the treatment is a miracle. She recovered significantly! Visit Naturalherbscentre. com
katherinebhana7 3y ago
I’m a little bit hesitant posting about my moms progress using Ayurvedic treatments but I’ll post in hope that someone finds this helpful despite the many herbal snake oil I see been advertise on this group. My mother who had been diagnosed with Lou Gehrig’s disease for 3 years at the age of 82 had all her symptoms reversed with Ayurveda medicine from natural herbs centre after undergoing their ALS/MND Ayurvedic protocol, she’s now able to comprehend what is seen and she no longer needs the feeding tube to feed,. God Bless all ALS disease Caregivers. Stay Strong, take small moments throughout the day to thank yourself, to love your self, and pray to whatever faith, star, spiritual force you believe in and ask for strength, their website is naturalherbscentre. com She’s getting active again since starting this treatment program...

137 points by kurthr 3y ago

This drug was approved after Phase II trials largely failed and a second review panel was convened to override the first. Now it has failed again in Phase III after being given to many hopeful patients at great cost. The last lines rang true: You need what you've always needed: efficacy and safety. Boring, tedious, expensive efficacy and safety. Desire and despair don't figure in much - in a much different universe, one whose physical laws respected and validated human emotions and human suffering, they would. But we don't live in that world.

deleted 3y ago
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echelon 3y ago
[flagged]
- jobs_throwaway 3y ago
  On an individual level that's rational, but on an institutional level the safeguards and caution are also rational. If you are able to make the drugs/experiments yourself, knock yourself out. But don't expect huge corporations/governments to do it for you
  - tiahura 3y ago
    Shouldn't the safeguards be inversely proportional to the level of untreatable misery?
    - JumpCrisscross 3y ago
      > Shouldn't the safeguards be inversely proportional to the level of untreatable misery? This is tautology’s Treatment is the variable. What constitutes the untreatable is the point of the question.
  - aeternum 3y ago
    The safeguards and caution are even more immoral from a rationalist point of view. By delaying potential medical breakthroughs you cause many future humans some amount of additional suffering because medical breakthroughs build on one another. If you delay an ALS cure by one year, you are not only harming all those who have ALS for that year but all those present and future humans that have other diseases that could benefit from the future research tree branching out from that ALS cure. Suppose for example that our ancestors were more risk-averse, more focused on the moral "do no harm" and thereby agreed upon 20 year trials for all new surgical procedures. What would 'modern' surgery look like? We should be celebrating the risk-takers as willingness to take an experimental drug or an experimental treatment as it is often a greater gift to humanity than an organ donation.
- thenerdhead 3y ago
  https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190...
  - echelon 3y ago
    This is exactly the right direction.
- caslon 3y ago
  There are other countries, ones where it's legal to do medical experimentation upon any consenting party. Unsurprisingly, they don't create significant amounts of novel drugs. Why? Because the US system is more profitable, and, similar to how writing proprietary software is the most common way to earn a living as a software engineer, people like money. Similar to platforms that claim to "democratize" a given hobby while at the end of the day being proprietary SaaS, people can claim as good of motives as they want, but at the end of the day, they want to make enough money to sit on their heels. The government strongly incentivizes drugs that are economically worthless without it. The US system ensures that everyone gets paid. Laissez-faire drug development wouldn't. As better in theory as it may be, just like free software, in practice, you'd probably get fewer returns than the controlled system, just because people aren't altruistic, and nobody cares about niche diseases that doesn't have direct motive.
  - echelon 3y ago
    Not once did I propose changing the economic model. Only that we should give consenting, perhaps eager, terminal patients more options in participating in research and access to promising new drugs. It's unfair that there's a decade of waiting when lives are so quickly and pointlessly lost. You're alive as a conscious participant in the universe just once, and then there's an infinity of nothing. You should have the option to try to keep that spark alive. If a chance, even fleeting, lies behind a glass door, that's cruel.
    - catlikesshrimp 3y ago
      If you did that, there would be a rush of (not necessarily) terminal patients signing up and mostly dieing anyways (hopefully of their terminal illnesses) There would be, as expected, a large contingent of patients who were poor, alone and maybe not very terminal. The very same reason which lead to the creation of ethics committes
- andrewflnr 3y ago
  Sometimes when you get a random stupid downvote, someone else will come along and fix it. I've been on both sides of that. But when you complain about it, that's pretty near a guarantee that I won't touch it. Because the point of downvotes is to suppress useless content, and complaining about how you're being "silenced" because someone downvoted you on a web forum definitely qualifies. You're not entitled to be heard. A forum is a shared space, so it doesn't work unless we all have a vote on what happens here. If you somehow create the universe where people have "complete control", and you say annoying or even boring stuff, you won't get downvoted, you'll just get blackholed. Do you think that'll feel better? Anyway, don't take downvotes so seriously. Some days the hive is just cranky.
  - sillysaurusx 3y ago
    More to the point, I was going to vouch the comment (which removes the flagged status) till I got to the edits. It’s not possible to vouch it in its current state, because at best I’d be making a mistake, and at worst I’d lose my vouch privileges. So you’re literally making it impossible to salvage your comment when you go off on rants about censorship. There are thoughtful ways to comment about the moderation. If you take the time to phrase things in a substantive non-emotional way, and ask yourself "what am I trying to communicate?" you often end up with something that won’t be flagged. But the combination of user flags and manual mod review with the vouch system adding even more variability means that it’s a tossup whether any given decision will be reversed (or even can be reversed, since e.g. this one can’t be). It’s best to think of it like a casino and not worry on the days the cards don’t favor you. Amusingly, the change to rank flagged comments above downvoted comments in an effort to push them to places less-seen has catapulted this subthread to the second top comment of the whole submission, which I haven’t seen before. HN never fails to surprise.
    - andrewflnr 3y ago
      Interesting. It wasn't flagged when I commented. So it got flagged, vouched, and flagged again? I hadn't heard of/seen that ordering change. Also interesting. Though I can't agree with your last line, HN is very predictable sometimes. For instance, any thread about dark matter is reliably a mess. :D
- deleted 3y ago
  [deleted]
thenerdhead 3y ago
How about we fix that with this? https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190... Give patients access and do the right science. Make sure it is safe and allow people the right to try.
- capitainenemo 3y ago
  In the case of the parent article drug, it claims it was the pressure of patient advocacy groups that got the drug approved. Giving people the right to try unfortunately at present means everyone else paying for it (or paying for the harm it causes), unless unapproved drugs were required to be covered by the individual on their own. " But ALS patients (or their insurance companies) had the chance to pay for a drug ($158,000/yr list, who knows what the real price was somewhere below that) for what is in the end a combination of two generic medicines. And they might as well have been given peppermint candy for all the good it did. ... patient advocacy groups took victory laps after Relyvrio was approved, and they were a big part of the pressure that made the FDA reverse its initial correct decision "
- peeters 3y ago
  Can you expand on this? This bill seems to enable exactly what the author is attacking: exploiting the desperate hopes of terminally ill patients to sell ineffective drugs. I agree with removing red tape and allowing accelerated trials when the drugs are for these purposes, but it seems like today, drug companies can make a profit off of selling snake oil. They already stand to benefit from the reduced regulations, so why allow them to sell the drug at all under these circumstances? If they're so confident in the efficacy, they should be willing to give the drug away for free to benefit from an accelerated path to approval. This bill seems to allow drug companies to continue to sell under these regulations, and in fact goes even further by removing most liability from them.
  - yieldcrv 3y ago
    > but it seems like today, drug companies can make a profit off of selling snake oil anybody can sell sugar pills or any 'generally approved as safe' consumptive good, repackaged as something big pharma is hiding from you

deleted 3y ago

[deleted]

msie 3y ago

It's crazy how this drug got approved despite the evidence. A mixture of greed from the drug manufacturer and wishful thinking from the afflicted. Ugh. I've lost my trust in the system.

frodo8sam 3y ago
Agree, the Alzheimer's and ALS treatments that were approved recently were both cases where the patient advocacy groups stopped listening to experts and ironically harmed the people they are trying to help. It shows how important it is that the FDA keeps some emotional distance from the people they are trying to protect.
- ta8645 3y ago
  That's an interesting narrative, but are you sure that's actually what happened? It seems to elide the role of the drug manufacturer who pays for all these trials in the first place. Why would they pay for such doomed trials, just for the emotional hopes of patients? Are they that irresponsible with their stockholder's money? If so, they should probably be ousted and replaced with people who have more business savvy. Or alternatively, this really didn't have anything to do with hopeful patients or their advocates, but rather the greed of the pharma companies, hoping to push through unproven drugs for the sake of profit. I don't have any special insight into which narrative is true, but we've seen a lot of the second narrative historically.
  - jfengel 3y ago
    They can't profit if it doesn't work. There is that bizarre case with the Alzheimer's drug, but that seems rare and not something they should pin their hopes on. It sounds to me as if the drugmakers and the patient advocates are coming from the same place. They are desperate for it to work, and will convince themselves of it on any thin evidence. Probably something like "it did X in a petri dish so it must work eventually." There are surely executives making a calculated risk, but I think they couldn't do it if there weren't also scientists who feed them over-optimistic guesses because they want it to work for the patients too.

light_hue_1 3y ago

We sometimes have posts here from patients who are desperate. And everyone dumps on the FDA in those threads. This is the flip side of that. This was patients lobbying Congress to skip safeguards. The FDA did not want to do this. https://apnews.com/article/science-business-health-lobbying-congress-08f90cb109edd90fd7dd94d608960a05 https://apnews.com/article/science-business-health-lobbying-... Now it's just getting worse and worse. ALS patient communities used the questionable approval of Aduhelm by desperate Alzheimer’s patients to strongarm the FDA into approving this. Every junk pharma product is now going to come with an advocacy group that says "let's just try it and see". Grifter pharma corporations will of course take advantage of this. They'll mobilize patient communities to keep skipping the science. And the result will be more wasted lives and more misallocated resources. Instead of working toward drugs that help people, we'll be working toward drugs that sound good to patient communities and Congress. This is a disaster. The FDA might be slow. But it's slow and deliberate for a reason.

rafaelero 3y ago
But what's the harm here? The drug is safe. The only burden patients had was financial. Now what if the drug was effective? The harm it would incur to patients by delaying it would be much more extreme.
- ejb999 3y ago
  the harm is not all drugs are safe - even if this one was (and we aren't 100% sure of that either), and pharma companies using social media and/or sympathy stories to pressure regulators into approving a drug that would not otherwise get approved is gross.
  - rafaelero 3y ago
    That's what Phase II is for.
- SoftTalker 3y ago
  Even if it's safe, the harm is in rewarding drug companies for producing very expensive products that don't work, and selling them to desperate people and their families who will sell off everything they own and go as far into debt as they can to pay for them. This creates incentives that we don't or should not want.

optimalsolver 3y ago

[flagged]

azinman2 3y ago
What would you rather have in this scenario? Earlier phases almost certainly started on animal models. How do you know it will or won’t work in humans if you don’t do clinical trials? Keep in mind 90% of drugs fail clinical trials, and that’s almost certainly after showing success in animal models.

dddddaviddddd 3y ago

> The Phase III trial has just read out, and Relyvrio shows no hint of actually working.... It did have a very good safety profile, fortunately, so it seems unlikely that anyone was physically harmed. Phase II trials are more about safety than efficacy, so I'd say the system worked as designed.

iechoz6H 3y ago
One wonders how they got as far as Phase III trials without actually working.
- zeroonetwothree 3y ago
  Phase III is when you test efficacy so it’s exactly how it’s meant to be
  - moritzwarhier 3y ago
    considering costs this doesn't sound very utilitarian
    - pc86 3y ago
      Why would you test something for efficacy before you're sure it's safe? You'll end up testing a bunch of harmful substances that don't actually do anything.
      - moritzwarhier 3y ago
        Fair point, although it also seems nonsensical to test safety for human consumption before having a robust hypothesis for desired effects. It's not true that safety is fast and easy to check.
      - SoftTalker 3y ago
        Maybe because the real standard is "the benefits out weigh the risks" you might want a drug that has a 10% chance of harm if it has a 90% chance of benefit, for a condition that is terminal if untreated.

dlevine 3y ago

There was a good article on this in the New Yorker a while back: https://www.newyorker.com/magazine/2023/06/26/relyvrio-als-fda-approval https://www.newyorker.com/magazine/2023/06/26/relyvrio-als-f... It's sad that the drug didn't work (and I had a cousin recently die of ALS), but it's important to let the FDA do their work.

thenerdhead 3y ago
What work does the FDA do here? It is the work of large investments or initiatives to prove safety and efficacy and the FDA makes decisions. If anything we live in a world where we need better provisions for these illnesses similar to https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190... Waiting for phased trials when you understand the research and hypothetical risks is torture. Especially when many drugs have proven safety profiles where the only harm is financial.
- ProjectArcturis 3y ago
  This particular drug was just a combination of two already-approved generic drugs. Anyone could have tried them with a doctor's Rx without a change in the law.
  - thenerdhead 3y ago
    Ah so a patent company who wanted to make a profit? https://www.regulations.gov/docket/FDA-2023-E-2605 https://www.regulations.gov/docket/FDA-2023-E-2605 Interesting!
    - downvotetruth 3y ago
      Infuriating that government site does not even display without JavaScript.
hash872 3y ago
>but it's important to let the FDA do their work The FDA has been 'working' on authorizing sunscreen widely used in the rest of the developed world for the last 20 years, or since the original Dubya administration. This is not a typo. They are glacially, bureaucratically slow & cautious

cat_plus_plus 3y ago

Said no patient ever. Everyone wants right to try, understandable that insurance would only cover sufficiently proven treatments. But if I can raise money, I want to at least take the most promising currently and if it doesn't work, oh well.

ryukoposting 3y ago
I think the important detail here is that, to anyone paying attention to the results of the clinical trials, this drug never showed promise in the first place. The system we have is slow because it's thorough. Sometimes we have to move faster, and that's what EUAs are for. The worst versions of "right to try" policy would open the floodgates to all kinds of quack drugs with astronomical price tags. The resulting system would extract money from the desperate, and do very little to cure the ill.
- thenerdhead 3y ago
  Not true. You can mark certain confirmed illnesses with provisions. Quacks won’t be allowed in such regulated environments. https://www.congress.gov/bill/118th-congress/senate-bill/1906/titles?s=1&r=44 https://www.congress.gov/bill/118th-congress/senate-bill/190...
  - marcinzm 3y ago
    > Quacks won’t be allowed in such regulated environments. Presumably, however, pharmaceutical companies striving to maximize shareholder value at all costs are allowed which is probably much worse in the end.
    - thenerdhead 3y ago
      Yes they are free to do that if their drugs work. That’s allowed in any capitalist market.
      - marcinzm 3y ago

karaterobot 3y ago

> An uncharitable view would be that Amylyx ended up presenting the clinical package from the only angle that made it even possible to believe that the drug worked, and the FDA advisory committee ended up voting against approval... I hate to be this way, but I continue to believe that unmet medical need is not by itself enough reason to approve a drug. You need what you've always needed: efficacy and safety. Boring, tedious, expensive efficacy and safety. I can either take from this that he believes the FDA and Amylyx were engaged in irresponsible behavior letting it get this far, or that (thank God!) an ineffective drug will not be approved, and we should all be glad there is a rigorous testing process that worked again. I get the sense that he believes the former, but can't ethically say so.

ProjectArcturis 3y ago
It's both. The FDA erred in approving this ineffective drug based on weak P2 data.

j7ake 3y ago

Failing so late in the drug process can literally bankrupt a company.

thenerdhead 3y ago
As it should. That’s the risk they take. Either you have a well designed trial that shows your drug is effective or you don’t. What you don’t do is make lofty promises to vulnerable patients.
StanAngeloff 3y ago
Amylyx Stock Wipes Out Nearly All Of Its Value, Crashing 82%, After Pivotal ALS Drug Failure[0] [0]: https://finance.yahoo.com/m/b15fb91a-1e90-3259-844e-cfdb256344de/amylyx-stock-wipes-out-nearly.html https://finance.yahoo.com/m/b15fb91a-1e90-3259-844e-cfdb2563...
- consp 3y ago
  Probably someone made money off it as according to the article this was the clear outcome.

sudosteph 3y ago

My Dad has ALS and has participated in a couple trials for different treatments. It's hard to say if any of them made a difference at all, and the justification behind some of these drugs seems extremely flimsy (one he was doing was for a drug that had some weak correlation during covid for slightly slower progression in one symptom), and the quality life impact of participating in that trial (having to fly to Boston, drug side effects, multiple lumbar punctures) leaves me frustrated that doctors recommend these at all. I feel like they're trading favors to get patients into studies with doctors they know, meanwhile, there are more promising ones that are being tested that he should be a candidate for, but the doctor won't even have a conversation about trying to get him in those trials. It leaves a bitter taste in my mouth. I hope something comes from all this, but right now I don't have a high view of the drug research and treatment process for this condition.

lambdaba 3y ago
I hope this is not inapropriate but I wanted to share this interview with a person using a high fat diet for ALS: https://youtu.be/GoF4GZ1NoBQ?si=Y-yEnquZsLXXb2po https://youtu.be/GoF4GZ1NoBQ?si=Y-yEnquZsLXXb2po Noting that ketogenic diets are already proven to improve outcomes in other neurodegenerative diseases.

randomgiy3142 3y ago

There are bigger things than a failed trial. There was a lot of money invested in this and when it was found to not be harmful there was a large push to show success. A lot of careers will be cut short because of this. There’s a lot of motivation to show something works. I was told to avoid research because of this kind of thing. There were a lot of highly paid people in a room that were not scientists but tasked with showing how much money could be made. That sounds evil but their intentions are good, that doesn’t help ALS people but there’s enough money put into this I wouldn’t be surprised if some progress is shown somewhere.

tibbydudeza 3y ago

ALS or as Americans call it Lou Gehrig disease is a high-profile disease because of the ice bucket challenge despite the low incidence (6 out of 100,000) compared to other diseases like coronary disease or some cancers. The disease is cruel, and it hits home for many of us as there are no mental deterioration like with dementia, Alzheimer's or FPD but you lose the ability to use your body and survival less than 3 years. I can see why the FDA and congress are desperate to be seen to do something.

katherinebhana7 3y ago

ALS is a cruel disease. My mum is 83 and had great difficulty speaking and swallowing much of anything. Food was getting trapped in her throat and blocking her air way was happening more often. she battled for each breath. The riluzole did very little to help her. The medical team did even less. Her decline was rapid and devastating. The psychological support from the medical centre was non-existent and if it were not for the sensitive care and attention of our primary physician, there she would have died. There has been little if any progress in finding a cure or reliable treatment. Acupuncture eased her anxiety a bit. this year our primary physician started her on Natural Herbs Centre ALS/MND Ayurvedic treatment, 6 months into treatment she improved dramatically. It has been a complete turnaround with her speech, she no longer needs the feeding tube to feed, the treatment is a miracle. She recovered significantly! Visit Naturalherbscentre. com

katherinebhana7 3y ago

I’m a little bit hesitant posting about my moms progress using Ayurvedic treatments but I’ll post in hope that someone finds this helpful despite the many herbal snake oil I see been advertise on this group. My mother who had been diagnosed with Lou Gehrig’s disease for 3 years at the age of 82 had all her symptoms reversed with Ayurveda medicine from natural herbs centre after undergoing their ALS/MND Ayurvedic protocol, she’s now able to comprehend what is seen and she no longer needs the feeding tube to feed,. God Bless all ALS disease Caregivers. Stay Strong, take small moments throughout the day to thank yourself, to love your self, and pray to whatever faith, star, spiritual force you believe in and ask for strength, their website is naturalherbscentre. com She’s getting active again since starting this treatment program...