15 ms·

Third member of U.S. FDA advisory panel resigns over Alzheimer’s drug approval

243 points by mrfusion 5y ago

m3kw9 5y ago
The approval is a bet that it could work because of the status quo regarding beta amyloid’s role in the disease. It‘a also a sign of human desperation on the fight against this if you zoom out. Thy are willing to throw anything at it that even have a slight chance. This is what it is about in my view.
- r00fus 5y ago
  The challenge is that a group of people are going to profit massively from this drug being approved. Some patients are going to pay $56K+ on this treatment, in other cases, we taxpayers are going to pay that (Medicare/Medicaid). Should this be approved if it's ineffective?
epmaybe 5y ago
I’m finding it really hard to understand how this met approval to ‘give patients an option’ when the government just recently passed laws to expand access for unapproved drugs. We even have expanded access programs that have been possible for years, with rapid turnaround when requested. Maybe it’s easy to understand and it’s about money? Or is this a policy shift in the FDA to just approve ‘safe’ medications and not necessarily hold marketing approval for futility.
- epmaybe 5y ago
  For those eventually reading the above comment at some point - I honestly forgot that the accelerated approval process exists, and that’s how this got approved. That basically means they get to say their drug was shown to affect surrogate markers (in this case, brain amyloid levels) and thus could be effective at treating symptoms, even though the trial was ended for futility. Feels like gaming the system in a way, and you can still market this very effectively without saying it can treat Alzheimer’s..”our drug was shown to reduce X, a key marker in Y”. I hate direct to consumer drug marketing.
nceqs3 5y ago
This was truly a terrible decision. Not a single member of the advisory committee would attach their name to this shit drug. 9 YEARS for a phase 4 trial! This decision will go down in history in the same league as the Addyi approval or Oxycontin label approval.
- TaylorSwift 5y ago
  Could someone please expand on the current outrage? Article did say "The 11-member committee voted nearly unanimously in November that Biogen's drug should not be approved, citing inconclusive evidence that the drug was effective.", but was wondering why the some would think otherwise for the approval.
  - curtis3389 5y ago
    It seems that the committee is an panel of outside advisors for the FDA. The advisors advised that Aduhelm should not be approved because it only helps with a likely contributor to Alzheimer's, and it doesn't actually help with Alzheimer's. The FDA ignored the panel and approved the drug anyways. I wonder about the financial incentives and the corruption in the FDA. Every drug maker wants to be the first with an approved Alzheimer's drug; there's a ton of money to be made there.
    - jhayward 5y ago
      > helps with a likely contributor to Alzheimer's There is no evidence, and plenty of failed trials, to indicate that Amyloid plaque is a cause of Alzheimers.
  - Majromax 5y ago
    Derek Lowe has a recent article on the subject (https://blogs.sciencemag.org/pipeline/archives/2021/06/08/the-aducanumab-approval https://blogs.sciencemag.org/pipeline/archives/2021/06/08/th...) that covers the issue in some detail by way of criticism. In short, the medication does appear to reduce the beta-amyloid plaque buildup in the brains of patients with Alzheimer's. However, in the phase 3 study that plaque reduction did not appear to result in any clinical improvement in patients. The Phase 3 trial was "stopped for futility." That's why the advisory panel could recommend rejection -- the drug did not appear to help patients. But equivalently, it did do the thing it set out to do, so that justified (ish?) the final approval.
cobrabyte 5y ago
> The 11-member committee voted nearly unanimously in November that Biogen's drug should not be approved, citing inconclusive evidence that the drug was effective. A near-unanimous vote against the drug, and the FDA moved forward with approval anyway? Like many others, I've experienced first-hand what Alzheimer's does to a person and the hopelessness in fighting it. Approving a drug that doesn't appear to do what it claims to do will provide false hope, and that's the worst thing you can give someone with Alzheimer's.
- walugipnts 5y ago
  it’s also $56k per year, not including the imaging required
  - vxNsr 5y ago
    It doesn’t, that was the suggested price. For anyone who is a candidate for this drug they will almost certainly be on Medicare or Medicaid and the gov negotiates a much lower price than retail.
    - s1artibartfast 5y ago
      This not correct. Medicare does not negotiate any drug prices and is explicitly banned from doing so. Instead medicaid pays the average price paid by private insurance, plus a flat markup % to the doctors office. https://medium.com/unraveling-healthcare/how-do-medicaid-and-medicare-set-drug-prices-83411811d632 https://medium.com/unraveling-healthcare/how-do-medicaid-and... The EU is different in that the national health services negotiate with companies based on patient benefit. This is illegal in USA
      - vxNsr 5y ago
        The article you link directly contradicts your claim: > So how do Medicaid and Medicare set drug prices? Medicaid takes the lowest negotiated price by private payers. After which, states have the right to further negotiate price. Aetna, Express Scripts, and Oscar Insurance all negotiate with pharma companies for the best price. Perhaps Aetna and Oscar only receive 20% discounts while Express Scripts receives a 30% discount. This 30% discounted price is now the Medicaid price. Additional requirements ensure this price level adjusts to inflation. Although the federal government helps fund Medicaid, it’s managed at the state level. At the state level, Medicaid can indeed negotiate further discounts with pharmaceutical companies. However, the federal government is still prohibited. While the fed might not be allowed to negotiate, states can and do. As can individual providers. Basically you’re making a bad faith argument and hoping I wouldn’t read your “source” Also Medicaid and Medicare are two different programs. The reason it doesn’t get too involved in Medicaid is bec it’s a state controlled program and would appear to be outside of their purview. EDIT:: I seem to be getting rate limited by HN due to downvotes so I’m gonna post my reply here: That’s false. Again, the amount paid is never the MSRP, not by Medicare and not by Medicaid. And generally not by any insurance company either. You’re intentionally making a bad faith argument. Both Medicare and Medicaid use negotiated pricing whether they negotiated those prices or someone else did. It is absolutely categorically false to state unequivocally or even imply that Medicare pays the MSRP. In the context of this discussion it is totally false to claim that any medical insurance provider (public or private) will be paying $56k for this drug. Not only because insurance companies don’t pay MSRP, but also because that price was set before all this happened, under these new circumstances BioGen will absolutely be updating their MSRP as well to reflect the new reality (drug is only proven to lower an Alzheimer’s marker and not directly treat the disease itself).
papito 5y ago
I hope everyone realizes now that the FDA is not a real regulatory agency. Regulations are written by the companies. At this point, the entire industry is essentially self-regulated. FDA is just a formality. Boeing 737 MAX, anyone? Yes, this is what happens when Big Evil Government is gone. People die.
- vxNsr 5y ago
  > Yes, this is what happens when Big Evil Government is gone. No this is exactly what big gov is. Every large system is corrupt. That’s human nature. Don’t for one second think you can create a better system that works around human nature. You will fail every time.
- refurb 5y ago
  As someone who has actually interacted with the FDA during a drug approval this is actually the opposite of how it works. Going to add this comment to the pile of “written in a tone of absolute certainty but completely wrong”.
- linuxftw 5y ago
  > Yes, this is what happens when Big Evil Government is gone. People die. This is Big Evil Government. Governments are bigger and more powerful than they've ever been.
  - hobs 5y ago
    Alright, then let's have regulated big government instead of unhinged corporatism.
    - deleted 5y ago
      [deleted]
    - unanswered 5y ago
      GGP comment literally just explained what "regulations" are: "corporatism", as you put it. And you want more of them? So you want more corporatism, to solve corporatism?
linuxftw 5y ago
What everyone's forgetting is we live in the information age. You think this stuff just started happening? No, you just started hearing about it. There have been countless whistle blowers over the years. What is it going to take for people to realize the entire industry is compromised from top to bottom? Why do you think some of us are refusing to take an experimental gene therapy drug? Nobody is ever going to tell you it was a failure, they will never admit they lied to you. The billionaires became trillionaires.
- deleted 5y ago
  [deleted]
whyIsItOk 5y ago
As great as the current US medical system is(ha), I'd love to see a near unregulated alternative that's entirely science based. We currently use Authority based medicine and that has caused unaffordable healthcare and the opiod crisis. If science based healthcare doesn't work, you'd still be able to visit a Physician. Feel free to argue the details, make sure you include getting heart transplants by a 18 year old science fan.
hirundo 5y ago
My take on this is counter-consensus. I don't believe that screening drugs based on effectiveness is a proper role for any government agency. There is a role for them to guard against fraud and to protect rights, but not to prevent people from making risky choices. Adults should not be protected from the decision to take any drug, however harmful, even if instantly fatal, if fraud or force is not involved. These are extraordinarily complex choices that seldom have a right answer for all possible patients. Therefore they should not be made centrally for everyone. We will learn more and faster from decentralized decision makers, that is, from massively parallel computation from a mass population of decision makers. Better would be for the only role of the FDA in decisions like this to be determining if the manufacturer is making fraudulent claims. Even better (because of greater computational parallelism) would be for this to be legally decided only by individual states. Best would be to treat adults as adults, and let them and their medical providers make such choices.
- nabla9 5y ago
  Your argument misses some of the important reasons of the approval process. Firstly, approval limits the legal liability for drugmakers. If we adopt a policy where approval does not exist. As long as the government takes part in the risk so it should have a say in the matter. > treat adults as adults, and let them and their medical providers make such choices. Signing out of medicare and all government assistance in case of becoming invalid, so that government is not in the hook for personal decisions would be a huge ask. If 10 million individuals make the same decision independently, and it backfires, that has negative consequences for the rest of the country. One decision does not matter, millions of decisions become collective matter.
- kesselvon 5y ago
  What a terrible idea. Nobody has the knowledge base to make a real informed decision on the efficacy of a drug. Not filtering for effectiveness is to endorse fraud and blame it on consumers when it happens. The whole reason the FDA is set up this way was due to the rampant fraud that was occurring before there were standards for what could be sold to consumers as medicine.
  - 5y ago
deleted 5y ago
[deleted]
mcguire 5y ago
"The 11-member committee voted nearly unanimously in November that Biogen's drug should not be approved, citing inconclusive evidence that the drug was effective. "The FDA on Monday gave the drug “accelerated approval,” based on evidence that it can reduce a likely contributor to Alzheimer’s, rather than proof of a clear benefit against the disease." Aren't we on the third or fourth round of "likely contributor to Alzheimer's" that turns out not to provide significant benefits?
gaetgu 5y ago
Is anyone else getting some "Rise of the Planet of the Apes" vibes? Questionable Alzheimers drug etc. etc.
flippinburgers 5y ago
And the price tag of the drug itself. Something to consider when there is doubt about the effectiveness.

243 points by mrfusion 5y ago

The approval is a bet that it could work because of the status quo regarding beta amyloid’s role in the disease. It‘a also a sign of human desperation on the fight against this if you zoom out. Thy are willing to throw anything at it that even have a slight chance. This is what it is about in my view.

r00fus 5y ago
The challenge is that a group of people are going to profit massively from this drug being approved. Some patients are going to pay $56K+ on this treatment, in other cases, we taxpayers are going to pay that (Medicare/Medicaid). Should this be approved if it's ineffective?

epmaybe 5y ago

I’m finding it really hard to understand how this met approval to ‘give patients an option’ when the government just recently passed laws to expand access for unapproved drugs. We even have expanded access programs that have been possible for years, with rapid turnaround when requested. Maybe it’s easy to understand and it’s about money? Or is this a policy shift in the FDA to just approve ‘safe’ medications and not necessarily hold marketing approval for futility.

epmaybe 5y ago
For those eventually reading the above comment at some point - I honestly forgot that the accelerated approval process exists, and that’s how this got approved. That basically means they get to say their drug was shown to affect surrogate markers (in this case, brain amyloid levels) and thus could be effective at treating symptoms, even though the trial was ended for futility. Feels like gaming the system in a way, and you can still market this very effectively without saying it can treat Alzheimer’s..”our drug was shown to reduce X, a key marker in Y”. I hate direct to consumer drug marketing.

nceqs3 5y ago

This was truly a terrible decision. Not a single member of the advisory committee would attach their name to this shit drug. 9 YEARS for a phase 4 trial! This decision will go down in history in the same league as the Addyi approval or Oxycontin label approval.

TaylorSwift 5y ago
Could someone please expand on the current outrage? Article did say "The 11-member committee voted nearly unanimously in November that Biogen's drug should not be approved, citing inconclusive evidence that the drug was effective.", but was wondering why the some would think otherwise for the approval.
- curtis3389 5y ago
  It seems that the committee is an panel of outside advisors for the FDA. The advisors advised that Aduhelm should not be approved because it only helps with a likely contributor to Alzheimer's, and it doesn't actually help with Alzheimer's. The FDA ignored the panel and approved the drug anyways. I wonder about the financial incentives and the corruption in the FDA. Every drug maker wants to be the first with an approved Alzheimer's drug; there's a ton of money to be made there.
  - jhayward 5y ago
    > helps with a likely contributor to Alzheimer's There is no evidence, and plenty of failed trials, to indicate that Amyloid plaque is a cause of Alzheimers.
- Majromax 5y ago
  Derek Lowe has a recent article on the subject (https://blogs.sciencemag.org/pipeline/archives/2021/06/08/the-aducanumab-approval https://blogs.sciencemag.org/pipeline/archives/2021/06/08/th...) that covers the issue in some detail by way of criticism. In short, the medication does appear to reduce the beta-amyloid plaque buildup in the brains of patients with Alzheimer's. However, in the phase 3 study that plaque reduction did not appear to result in any clinical improvement in patients. The Phase 3 trial was "stopped for futility." That's why the advisory panel could recommend rejection -- the drug did not appear to help patients. But equivalently, it did do the thing it set out to do, so that justified (ish?) the final approval.

cobrabyte 5y ago

> The 11-member committee voted nearly unanimously in November that Biogen's drug should not be approved, citing inconclusive evidence that the drug was effective. A near-unanimous vote against the drug, and the FDA moved forward with approval anyway? Like many others, I've experienced first-hand what Alzheimer's does to a person and the hopelessness in fighting it. Approving a drug that doesn't appear to do what it claims to do will provide false hope, and that's the worst thing you can give someone with Alzheimer's.

walugipnts 5y ago
it’s also $56k per year, not including the imaging required
- vxNsr 5y ago
  It doesn’t, that was the suggested price. For anyone who is a candidate for this drug they will almost certainly be on Medicare or Medicaid and the gov negotiates a much lower price than retail.
  - s1artibartfast 5y ago
    This not correct. Medicare does not negotiate any drug prices and is explicitly banned from doing so. Instead medicaid pays the average price paid by private insurance, plus a flat markup % to the doctors office. https://medium.com/unraveling-healthcare/how-do-medicaid-and-medicare-set-drug-prices-83411811d632 https://medium.com/unraveling-healthcare/how-do-medicaid-and... The EU is different in that the national health services negotiate with companies based on patient benefit. This is illegal in USA
    - vxNsr 5y ago
      The article you link directly contradicts your claim: > So how do Medicaid and Medicare set drug prices? Medicaid takes the lowest negotiated price by private payers. After which, states have the right to further negotiate price. Aetna, Express Scripts, and Oscar Insurance all negotiate with pharma companies for the best price. Perhaps Aetna and Oscar only receive 20% discounts while Express Scripts receives a 30% discount. This 30% discounted price is now the Medicaid price. Additional requirements ensure this price level adjusts to inflation. Although the federal government helps fund Medicaid, it’s managed at the state level. At the state level, Medicaid can indeed negotiate further discounts with pharmaceutical companies. However, the federal government is still prohibited. While the fed might not be allowed to negotiate, states can and do. As can individual providers. Basically you’re making a bad faith argument and hoping I wouldn’t read your “source” Also Medicaid and Medicare are two different programs. The reason it doesn’t get too involved in Medicaid is bec it’s a state controlled program and would appear to be outside of their purview. EDIT:: I seem to be getting rate limited by HN due to downvotes so I’m gonna post my reply here: That’s false. Again, the amount paid is never the MSRP, not by Medicare and not by Medicaid. And generally not by any insurance company either. You’re intentionally making a bad faith argument. Both Medicare and Medicaid use negotiated pricing whether they negotiated those prices or someone else did. It is absolutely categorically false to state unequivocally or even imply that Medicare pays the MSRP. In the context of this discussion it is totally false to claim that any medical insurance provider (public or private) will be paying $56k for this drug. Not only because insurance companies don’t pay MSRP, but also because that price was set before all this happened, under these new circumstances BioGen will absolutely be updating their MSRP as well to reflect the new reality (drug is only proven to lower an Alzheimer’s marker and not directly treat the disease itself).

papito 5y ago

I hope everyone realizes now that the FDA is not a real regulatory agency. Regulations are written by the companies. At this point, the entire industry is essentially self-regulated. FDA is just a formality. Boeing 737 MAX, anyone? Yes, this is what happens when Big Evil Government is gone. People die.

vxNsr 5y ago
> Yes, this is what happens when Big Evil Government is gone. No this is exactly what big gov is. Every large system is corrupt. That’s human nature. Don’t for one second think you can create a better system that works around human nature. You will fail every time.
refurb 5y ago
As someone who has actually interacted with the FDA during a drug approval this is actually the opposite of how it works. Going to add this comment to the pile of “written in a tone of absolute certainty but completely wrong”.
linuxftw 5y ago
> Yes, this is what happens when Big Evil Government is gone. People die. This is Big Evil Government. Governments are bigger and more powerful than they've ever been.
- hobs 5y ago
  Alright, then let's have regulated big government instead of unhinged corporatism.
  - deleted 5y ago
    [deleted]
  - unanswered 5y ago
    GGP comment literally just explained what "regulations" are: "corporatism", as you put it. And you want more of them? So you want more corporatism, to solve corporatism?

linuxftw 5y ago

What everyone's forgetting is we live in the information age. You think this stuff just started happening? No, you just started hearing about it. There have been countless whistle blowers over the years. What is it going to take for people to realize the entire industry is compromised from top to bottom? Why do you think some of us are refusing to take an experimental gene therapy drug? Nobody is ever going to tell you it was a failure, they will never admit they lied to you. The billionaires became trillionaires.

deleted 5y ago
[deleted]

whyIsItOk 5y ago

As great as the current US medical system is(ha), I'd love to see a near unregulated alternative that's entirely science based. We currently use Authority based medicine and that has caused unaffordable healthcare and the opiod crisis. If science based healthcare doesn't work, you'd still be able to visit a Physician. Feel free to argue the details, make sure you include getting heart transplants by a 18 year old science fan.

hirundo 5y ago

My take on this is counter-consensus. I don't believe that screening drugs based on effectiveness is a proper role for any government agency. There is a role for them to guard against fraud and to protect rights, but not to prevent people from making risky choices. Adults should not be protected from the decision to take any drug, however harmful, even if instantly fatal, if fraud or force is not involved. These are extraordinarily complex choices that seldom have a right answer for all possible patients. Therefore they should not be made centrally for everyone. We will learn more and faster from decentralized decision makers, that is, from massively parallel computation from a mass population of decision makers. Better would be for the only role of the FDA in decisions like this to be determining if the manufacturer is making fraudulent claims. Even better (because of greater computational parallelism) would be for this to be legally decided only by individual states. Best would be to treat adults as adults, and let them and their medical providers make such choices.

nabla9 5y ago
Your argument misses some of the important reasons of the approval process. Firstly, approval limits the legal liability for drugmakers. If we adopt a policy where approval does not exist. As long as the government takes part in the risk so it should have a say in the matter. > treat adults as adults, and let them and their medical providers make such choices. Signing out of medicare and all government assistance in case of becoming invalid, so that government is not in the hook for personal decisions would be a huge ask. If 10 million individuals make the same decision independently, and it backfires, that has negative consequences for the rest of the country. One decision does not matter, millions of decisions become collective matter.
kesselvon 5y ago
What a terrible idea. Nobody has the knowledge base to make a real informed decision on the efficacy of a drug. Not filtering for effectiveness is to endorse fraud and blame it on consumers when it happens. The whole reason the FDA is set up this way was due to the rampant fraud that was occurring before there were standards for what could be sold to consumers as medicine.
- 5y ago

deleted 5y ago

[deleted]

mcguire 5y ago

"The 11-member committee voted nearly unanimously in November that Biogen's drug should not be approved, citing inconclusive evidence that the drug was effective. "The FDA on Monday gave the drug “accelerated approval,” based on evidence that it can reduce a likely contributor to Alzheimer’s, rather than proof of a clear benefit against the disease." Aren't we on the third or fourth round of "likely contributor to Alzheimer's" that turns out not to provide significant benefits?

gaetgu 5y ago

Is anyone else getting some "Rise of the Planet of the Apes" vibes? Questionable Alzheimers drug etc. etc.

flippinburgers 5y ago

And the price tag of the drug itself. Something to consider when there is doubt about the effectiveness.