> 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.
It sounds outrageous when phrased like that. But turns out there's ways of describing what happened that make it sound like a completely reasonable decision as well. See e.g. this forum post:
Which of the two groups of experts is right? I certainly don't have the experience to tell. But it seems plausible that both are acting in good faith, and there is no need for outrage.
That linked post is fundamentally wrong because it rests on an assumption that has essentially zero human evidence: amyloid causes Alzheimer’s. There have been several drugs that very efficiently reduce amyloid, strictly zero (including this one) have ever shown any benefit patient health even when running long trials (the Biogen trials started in 2015 and were halted for futility). There’s reason to believe the amyloid hypothesis is flawed, meaning that approving a drug that reduce amyloid is not going to help anyone, and will likely hurt people (through side effects).
If competing experts are the question, note that 3 actual experts have resigned from what are coveted positions in protest. Nearly every part of the pharma industry (including the press, investors, other companies) who doesn’t stand to profit (I.e. not Biogen) has been up in arms saying this is an awful decision using words such as “horrifying”. There is no expert disagreement.
People can try to ret-con this by saying it’s like HIV, but note that viral load is a pretty good marker for disease morbidity in most viral infections. Amyloid is nothing like that as a validated marker for disease burden.
The author of that post (magnet) mentions the amyloid debate later in that same thread.
That forum post advises "new drugs aimed at preventing Alzheimer’s should probably target surrogate markers rather than trying to fix the end-stage clinical problems".
Here's One Weird Trick for targeting Alzheimer's, to try at home. Grey hair is correlated with Alzheimer's. Hair dye is a treatment that targets that particular biomarker, with remarkable efficacy. How about we all use hair dye, in the hope it prevents Alzheimer's! Way cheaper than $56k/year too.
I'm wildly speculating here, but what if dying one's hair increases the odds of getting more romantic action (and thus more social relationships), which itself is associated with increased cognitive flexibility? If Alzheimer's is a lifestyle disease of an unfulfilling, unstimulating life, maybe the key is to seize each day?
Was showing all the symptoms of early onset Alzheimer’s. I was even responding some to dementia drugs.
Started blood thinners for unrelated reasons.
My dementia was gone in a few days. Turned out it was a clotting disorder.
Some dementia can have very different causes.
What is the second group of experts you're talking about?
Those who do not believe amyloid is a cause, but rather a symptom.
Surely it has nothing to do with the fact that the drug costs over $50,000 per year? Amirite?
The FDA didn't give it a full approval. It was an accelerated approval that basically said "This drug has been shown to help biomarkers that are associated with Alzheimer’s, but it's unknown if it helps with Alzheimer’s itself. While more evidence is collected, Biogen can distribute it."
Which is reasonable to me. It takes years to test drugs like this and if a patient and her doctor believe this is the best treatment, the FDA shouldn't prevent them from getting access to it.
Okay, but Biogen has 9 years to do the confirmatory study and they've indicated that they'll take their sweet, sweet, time with it. Also, it's not like we have 0 evidence: we have two, 4-5 year long studies that show how well it works: and the benefit in one was marginally positive and the effect of aduhelm was negative in the other.
Sarepta's Eteplirsen was in a similar situation: little data to back it up and a very controversial decision. They also had to do confirmatory studies, but it took them 3 years after the approval was done for the study to begin.
They did test this drug for years, the conclusion was that the drug does absolutely nothing for Alzheimer's. A big part of what FDA approval means is that it's been confirmed that the drug does what the makers of the drug claim it does. If that weren't the case, many drugs that have not been approved over past decades would have been.
This right here. People move cross country or even internationally for a chance to be in the 1 hospital who is running a trial for some non-proven drug for their disease
Being able to get the drug wherever you are in the U.S is a good step, and every patient/doctor can decide if they want to try it
> Being able to get the drug wherever you are in the U.S is a good step, and every patient/doctor can decide if they want to try it
FDA approval is for letting companies market a drug to the public, it has nothing to do with whether you as a patient are allowed to take it.
> Which is reasonable to me. It takes years to test drugs like this and if a patient and her doctor believe this is the best treatment, the FDA shouldn't prevent them from getting access to it.
I can understand this argument as long as Biogen isn't making any money off of these drugs. In fact, they should really be losing money if anything since they are gaining value from the data.
Big Pharma bad, but making drugs is incredibly costly. Especially in Alzheimers, where so many candidates failed. It's incredible someone is even trying after so many failures.
The big question is will insurance companies and CMS pay for it, and that's not up to the FDA. That debate is occurring right now and will likely create new precedents.
It really depends. I think that not being able to access a drug because the FDA cites inconclusive research could also be terrible.
Obviously you'd have to balance the risks of side effects with the chances of effectiveness.
But for a drug with really rare and mild side effects by all means you should be able to try it if you want to without becoming a criminal
It's entirely self-consistent to believe that the FDA shouldn't be a gatekeeper over what people can try, and also belive that as long as they maintain that gatekeeper role and don't just approve everything non-toxic then it's harmful for them to approve one specific drug that has no effect. If they purport to be a trusted signal of what works and what doesn't, then their approval is an endorsement, and in this case that endorsement is passing off noise as signal.
I want to burn drug dealers at the stake. By all means, I should be able to try that without becoming a criminal.
Do you feel the same about access to HCQ and Ivermectin?
No the OP, but if they were the only things around that showed any possibility of combating Covid, sure. But that's not the case. We have vaccines and other therapeutics that show incredible effectiveness. Approving HCQ and Ivermectin in this situation is wrong.
Off-topic: Touting worm medicine (I've only heard of it used for heartworm in dogs, but apparently it's also for human worms) as a Covid cure has to be the work of some troll that got out of hand. I might be out of the loop but it seems like this came out of nowhere.
it’s also $56k per year, not including the imaging required
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.
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.
The EU is different in that the national health services negotiate with companies based on patient benefit. This is illegal in USA
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.
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.
> Nobody has the knowledge base to make a real informed decision on the efficacy of a drug.
This is probably true for most patients, but not doctors. Normally, a patient consults a doctor on what drugs to use for their illness and the risk of taking it.
This is the idealized spherical cow theory of medicine. Doctors have more knowledge but it’s not any more reasonable to expect them to follow the scientific literature for hundreds of different topics than it is to expect the average HN reader to follow the standards and development process for every technology they use. This is especially true given the amount of money at stake: a company has enormous windfalls if they can convince doctors to prescribe it and there’s plenty of evidence showing that they’ll try everything to do that. The amount of money going into sales to doctors & advertising is similar to their R&D spend and there’s no reason to expect the steady stream of ethical complaints would go down with less regulatory oversight.
Doctors are doctors not research scientists. They are much more akin to engineers than scientists. There is also a massive amount of specialization in medicine (but not always in prescribing of medicine). Doctors absolutely rely on the work of scientists to help guide them. Doctors are not really trained in how to gauge the efficacy of medicines.
Isn't it more or less fact that doctors are (for obvious reasons) the target of marketing campaigns by the pharma industry to encourage prescribing certain products? Yes, doctors presumably have a higher degree of informedness/resistance to bullshit, but I think you are fooling yourself if you believe that everything is fine with doctors as the thing standing between you and the obvious financial incentives of the pharma world.
The only two options are not either that the FDA screens and approves drugs or it being down to individuals (or even these individuals' doctors). We could have private screening and trials companies that the drug producers themselves would pay. We already see this in other industries where there are both public and private inspections done. I've heard in those cases the private inspectors are actually stricter as well, as they actually have more incentive to be correct.
>Nobody has the knowledge base to make a real informed decision on the efficacy of a drug.
Informed decisions are not risk-free decisions. If you're saying that literally no one can provide informed consent to take a drug until years and years of trials have been performed, and their inability to provide informed consent invariably subjects them to functional degradation or death, then this is a perverse system, to say the least.
Note that many people made the same arguments against fast-tracking COVID vaccines for public distribution, which undoubtedly saved thousands if not millions of lives.
The FDA was required to approve all new drugs because of this: https://en.wikipedia.org/wiki/Thalidomide
I personally agree that the FDA isn't always perfect (they should never have approved SSRI's, for instance) but claiming that there's no tradeoff here is just incorrect.
The problem is that it costs $56k/year. Most people don't have that kind of money, so for the most part we're talking about whether that cost should be socialized, either via insurance or the government. That's an awful lot of money that could be used to treat a lot of other sick people. So it's not primarily a question of whether people should be allowed to take risks, it's more a question of how best to allocate finite resources.
Sure, but that is also not a question FFA should be answering.
I am a smart person, and I am not remotely qualified to make decisions about the risks associated with an untested drug. I’d like to know when I get a prescription that someone else went through the process of being a willing volunteer in a clinical trial.
Your doctor should be able to help with that and provide you only drugs that have completed clinical trials to your desired standard.
Frankly, I think most doctors aren't qualified to make such a decision by virtue of lacking PhDs: their expertise is in clinical care, not in evaluating research.
Doctors heavily rely on FDA to filter for effective drugs, they're not researchers with the skills to identify whether a drug has efficacy.
Your doctor is a smart person too but they can't simply check every single medication single handily. What even is "your desired standard" here?
> Better would be for the only role of the FDA in decisions like this to be determining if the manufacturer is making fraudulent claims.
Let us recall some of the key facts about the drug in question here. There were two trials. One of them showed such little benefit that it was halted midtrial on the basis that it would be unethical to continue giving people a drug that didn't work. The second showed marginal benefit.
Biogen argued that there is a rational explanation that explains the two trials that points to the drug working. The expert committee at the FDA had 10 people vote "that's bunk", 1 person vote "unsure", and nobody vote "I agree." That's a pretty strong endorsement for saying "Aduhelm treats Alzheimer's" is a fraudulent claim, and yet the FDA decided that the claim is merely disputed.
The only way you can look on the FDA's decision favorably is if you know nothing about how drug development works, which is unfortunately true of almost the entire public. (Here's two facts that are important to keep in mind: most drug candidates don't work, and placebo effects are very real and surprisingly powerful).
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.
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.
Derek Lowe has a recent article on the subject (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.
It's worrisome because this sort of thinking - "We don't have proof that it treats the actual disease, but it does seem to treat with this thing that we think might be (but have yet to prove actually is) a cause of the disease, so let's forge ahead anyway." - has led to so many instructive case studies in purported cures that ended up being worse than the disease. It's a complete abdication of what should be basic scientific and medical principles to decide that an un- or ill-evaluated hypothesis is good and run with it, on no firmer ground than the fact that you happen to be quite fond of this particular hypothesis.
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.
> 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.
I highly recommend the piece by Derek Lowe down thread, but the tldr is basically that researchers have believed amyloid plaques cause the symptoms of Alzheimer's and so the theory is that if you eliminate them, you can treat the disease. This drug gets rid of them. But the gold standard is whether or not the drug actually helps people, not whether it meets a technical definition of "working".
This is the drug equivalent of an engineer following a requirements document and saying to a product manager, "Hey, you said the form has to be submitted through the website. You can see here when I hit submit, it submits! The website doesn't save the data anywhere because that wasn't in the requirements".
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.
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.
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?
And the price tag of the drug itself. Something to consider when there is doubt about the effectiveness.
Is anyone else getting some "Rise of the Planet of the Apes" vibes? Questionable Alzheimers drug etc. etc.
Get a daily email with the the top stories from Hacker News. No spam, unsubscribe at any time.