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

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

reuters.com

243 pointsmrfusion204 comments

> 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’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.

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

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).

The part you quoted is specific to Medicaid, and what I said is accurate for Medicare.

The greater point also stands, which is that the fed doesnt negotiate prices, and is not lower than retail.

>Medicare or Medicaid and the gov negotiates a much lower price than retail

Follow up:

I agree msrp is rarely paid. Even the uninsured can often get manufacturers discount. You raise a good point that there is a possibility that biogen will update msrp, but I wouldn't hold my breath.

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:

https://forum.quartertothree.com/t/wtf-is-going-on-at-the-fd...

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.

Useful sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797629/#s3titl...

https://endpts.com/what-does-a-clear-majority-of-the-biophar...

The author of that post (magnet) mentions the amyloid debate later in that same thread.

https://forum.quartertothree.com/t/wtf-is-going-on-at-the-fd...

Even if the amyloid hypothesis is true (and most neuroscientists I know think it's not), this is a terrible decision.

1.) We don't know when to give the drug. Maybe giving it even earlier would help, but these trials don't tell us that. Answer: Run a new trial.

2.) We don't know how much drug to give. The drug was approved on the (bad, weak) evidence that in one high dose arm of one of 2 trials, there might have been an effect. Is that the right dose? Who knows! In the other trial, the high dose may have actually been worse. You can't titrate dosage in Alzheimers like you do in cancer where you can just watch how the tumor is shrinking. Answer: Run a new trial.

Giving this drug is not without downsides. You will have side-effects, including serious ones such as potentially brain swelling. Some people may be seriously injured or killed as a result of taking this drug. You have to make sure that the benefits outweigh that downside, and the trials show us a very dubious, weak effect.

The FDA should have said, "Good work, maybe there's an effect with this dosage, go run a new trial with the revised protocol." That's the right call.

Instead, they added, "Oh and you can sell the drug in the meantime and you don't have to tell us for 9 years."

How are you going to recruit patients for the trial? "We could give you the drug, but might give you a placebo." How many patients sign up for that instead of saying, "OR I could go out and buy the drug (which you claim totally works, and the FDA agrees!) independently."?

What if the trial fails in 9 years after you have tons of anecdotal reports (remember placebo shows an effect in past trials)? Now you have to take if off the market, imagine the loss of credibility that will entail for the FDA.

How about other drugs that reduced amyloid but showed no cognitive effect? (Eli Lilly's Solazenumab among many, many others) Should they get approved now too?

This is a mess for everyone and benefits Biogen. Everyone else loses, even the well-meaning patient advocates who created the political pressure for this decision.

Additional sources:

https://www.clinicaltrials.gov/ct2/show/NCT01900665

https://blogs.sciencemag.org/pipeline/archives/2019/12/06/th...

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?

> If Alzheimer's is a lifestyle disease of an unfulfilling, unstimulating life, maybe the key is to seize each day?

Yes, improve your social relationships and cognitive health by joining a nunnery or monastery! https://en.wikipedia.org/wiki/Nun_Study

Hey, it's worth trying! :)

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.

I'm close to multiple people with Alzheimer's. I think the worst thing you can give them is nothing as their personality evaporates and they become a husk of who they once were and a burden on everyone around them.

I can walk 5 minutes down the block and buy an eight ball of fentanyl from a guy named TJ but I can't get Alzheimer's treatment made by a team of scientists in a cutting-edge lab because it doesn't meet some government worker's idea of "good enough"?

I don't care what your bureaucratic panel thinks about how inconclusive the data is. My mother is dying.

And charging your mother $90,000 for a drug that does nothing at all isn’t a fix.

Mom's on social security she doesn't hasn't paid for any medical procedure in years. Have you heard of Medicare? Medicaid? You don't know what you're talking about at all selectodude.

Are Medicare or Medicaid covering Aduhelm to treat Alzheimer's? I don't know how the flow goes from FDA approval to certification for use by the government-administered insurance programs.

That would be Biogen's next step, politically speaking: use public pressure ("They're preventing us from getting a drug that might help!") to force Medicare to cover it.

I hope you can find peace. I’ve been in your situation and I understand the desperate hope for anything at all that has even a chance of working.

Be well.

Thank you <3

Sorry, but how does the fact that the government pays for your mother's healthcare make your position more defensible?

> I can walk 5 minutes down the block and buy an eight ball of fentanyl from a guy named TJ but I can't get Alzheimer's treatment made by a team of scientists in a cutting-edge lab because it doesn't meet some government worker's idea of "good enough"?

You're implying that "some government worker" is too incompetent to have the power to regulate experimental drugs. And now you're arguing that it'd be cool for those same government workers to rubber stamp approve and also pay for drugs that don't have the backing of scientific evidence, which is the textbook archetype of "incompetent government worker".

Not that your hypothetical question makes any sense. "TJ" selling fentanyl down the block is illegal. Biogen selling this unapproved drug is illegal. You have the same ability and legal issues to try to buy from them.

This is going to sound harsh, but the fact that other people (government/tax payers) are paying for it makes this even less defensible - wasting your own money on treatments that is likely to not work is one thing, but this risks diverting a shared resource from treatments that _do_ work.

I recently lost my grandfather to vascular dementia, so I understand the feeling of hopelessness, but this is not a solution. I'd _perhaps_ support your right to buy the drug privately, but this would open others up to scams and treatments that have no chance of working (or are in fact harmful). This isn't the same as the war on drugs, where people wanting to buy a particular drug are stopped for (largely) moralistic reasons - this is about ensuring the drug does what the company claims and protecting desperate people from being ripped off.

And that's exactly why it should not be approved. There is no proof there is ANY effect on the disease outcome. The trial was halted prematurely for futility ffs! And now the FDA is giving people false hope? Letting them spend $65k/year for possible snake oil with no scientific evidence behind it?

Alzheimer's is a terrible disease. And I get it, you're willing to try anything for a possible improvement. Problem is, there is no proof at all that aducanumab leads to any kind of improvement: only stuff that you might find if you do tons of data mining to get the result you want. If the drug was that good, you would find it each and every time you try it, not one out of a hundred times if you look at a subset of a subset.

The only reason the Biogen wants approval of this drug, is to earn money out of desperate people willing to try anything. The FDA should be there to protect people from this. They have failed to do that here.

The FDA doesn't prevent people from taking herbal supplements, given the supplement doesn't make misleading claims. Assuming this drug doesn't make misleading claims about the evidence for its effectiveness, why should the FDA prevent its sale?

Herbal supplements aren't considered drugs by the FDA, and thus are regulated under a different set of rules. What you asked makes as much sense as, "Why won't my doctor prescribe me a breakfast of steak and eggs?"

Say a breakfast of steak and eggs was classified as a drug, and it wasn't shown in a clinical setting to be effective in treating Alzheimer's. A doctor wants to prescribe it to a patient, even though the patient and doctor both know about the trials and evidence. Why should the FDA prevent the doctor from prescribing steak and eggs for breakfast?

Edit: I ask this because my understanding is that the FDA is supposed to make sure drugs are safe and also to oversee drugs of abuse. If a drug is deemed safe and isn't one that's likely to be abused, I don't understand why it's within the FDA's domain to tell a doctor whether they can prescribe it.

That would be considered off-label prescription.

Which is commonly done, and legal, right?

Yes, doctors can prescribe off-label uses for basically any already approved drug. I'm not sure how it would apply to Aduhelm, which AFAICT has no indicated uses other than Alzheimer's.

But let's assume there is no legal barrier to the doctor prescribing Aduhelm, and somehow you've found a doctor who is going to against the status quo based on inconclusive studies. Which insurers are covering it (certainly not Medicaid or Medicare)? Which pharmacy is stocking it? And where are they getting their supply? Biogen? You think Biogen's lawyers and executives are going to accept high legal exposure (e.g. consumer lawsuits) for an infinitesimally small market?

FDA approval provides a legal and market framework for drugs to be supplied, marketed, and paid for. If your friend who runs Biogen has a spare box of Aduhelm and gifts it to you, it wouldn't be the FDAs problem.

And in your hypothetical example, should insurance companies be required to cover this treatment? In other words, should other insurees be required to pay for it?

It depends on whether or not the insurance company determines it's of value enough to their customers to include it in their insurance package. Insurance companies don't insure all prescription drugs.

I think my comparison was too absurd/convoluted, because you're still making the same fundamental categorical mistake of asking "Why can't [X] be treated as [Y]?", as if "food" and "drugs" are just synonyms, and not separate categories with different rules and preconditions. But in any case, in a universe where "steak and eggs" were classified as a drug, and have also been commonly sold over-the-counter (i.e. at your local diner, without needing a doctor prescription), then nothing would prevent your doctor from prescribing "steak and eggs" for Alzheimers. And in our current universe, nothing stops your doctor from prescribing Viagra or Tylenol to treat Alzheimer's, even though none of those drugs have been approved by the FDA for that specific use. Doctors have a lot of freedom to use their judgment in prescribing off-label uses. So it's not a question of "Why can't doctors prescribe steak and eggs/Viagra/Tylenol" for my Alzheimer's — it's "Why won't...?", which I think the answer is mostly self-evident.

So why can't Aduhelm be treated like an OTC herbal supplement? Well for starters, because Biogen didn't research and develop it with the intention of marketing it as a herbal supplement. So I think the answers to your question are very much related to the answer to "Why doesn't Biogen release Aduhelm as a herbal supplement?"

Obviously we can dodge the question of "Why can't [X] be treated as [Y]?" by saying "X is not Y", as you've done. If you ignore the point behind the comparison, and we say that "X is X", then there is no argument. Biogen still has time to do the trial to show effectiveness and is going through a process that is governed by the set of rules set forth for drugs (not herbal supplements).

Sorry, I didn't say you can't consider Aduhelm to be an herbal supplement, just that every premise and factor in the current discussion would be rendered irrelevant.

So OK, let's agree that Aduhelm is now an herbal supplement. The FDA no longer has the authority to ban it from Walgreens. What's your point? The FDA's decision is about Aduhelm's proven effectiveness as a drug, and it has no bearing on whether Biogen wants to sell it as OTC herbal supplement. Do you believe the FDA is what's preventing Biogen from doing that right now?

The OP was saying how by allowing the accelerated approval, the FDA failed to protect people from a drug that hasn't yet been shown to be effective. My point was that it's not like the FDA protects people from snake oil anyway. Doctors can already get their patients to spend tons of money on unproven treatments. As long as the treatment isn't lying about what the evidence has shown, adults and their doctors are able to make decisions based on available information, and generally society is ok with that. That sentiment conflicts with OP's sentiment. That is why the comparison is relevant to the discussion.

>Herbal supplements aren't considered drugs by the FDA

And what is considered a drug or not is at the discretion of the FDA and other agencies. This is a choice they make not to regulate supplements like drugs. This fact has no bearing on what level of regulation is appropriate for a given chemical. Don't avoid the meaningful discussion by citing trivia.

See my reply further down the thread: https://news.ycombinator.com/item?id=27475833

You're right the FDA decides those categories. But Biogen is the one that created the compound and is pitching it as a drug, when they could've sold it as a nutritional supplement. Why exactly do you think they did that?

The difference is that insurance doesn't cover herbal supplements, so their cost isn't socialized. If insurance covers this treatment, then by extension everyone who has insurance has no choice but to pay for it.

That's true of some drugs anyway, especially newer ones where the effectiveness isn't as well studied.

>Problem is, there is no proof at all that aducanumab leads to any kind of improvement

Nothing you have said has any bearing on whether someone who is currently dying of Alzheimers should be allowed to try it if they or their doctors or family choose. "False hope" is not the most important thing at stake here, not by a long shot.

Committing fraud against the most desperate, vulnerable people in the country is universally regarded as unethical.

But there is no fraud. As has been stated elsewhere in this thread, the drug claims to remove plaque, not to treat Alzheimers. I personally don't have the hubris to think I should stand in the way of someone willing to try the drug on their loved one who is suffering from Alzheimers.

This is an incredibly expensive treatment meant for incredibly desperate people. If you were in a situation where a parent had alzheimers it would be hard not to feel guilty if you didn't try it, no matter the price.

To approve the drug despite the lack of efficacy is unethical, especially considering there are potentially severe side effects like brain swelling.

except that financial resources are finite . Without certain standards, costs would spiral out of control more than they already have.

I am sympathetic to the argument that expensive treatments socialized medicine pays for should be limited to those proven effective. What I am against are blanket restrictions presumably for people's own good, or to prevent "Big Pharma" from profiting or whatever bugaboo it is.

We can create combinatorially many drugs. There are labs that can screen hundreds of thousands of molecules a day. So approving drugs that aren’t proven effective for a disease might reasonably lead to few or no drugs that are effective because it’s so easy and relatively cheap to stuff a development pipeline with promising drugs if you don’t need to worry about whether they work at the disease stage due to crowding out effective drugs.

Sorry to hear that about your close family/friends. However, vouching for a rushed approval based on emotions is why such panels exist. That quality assurance is extremely important, especially with respect to drugs. Keep in mind the worst case scenario: the drug does not work, the drug causes adverse side effects, AND it costs money.

I'm so sorry for your struggles and those of your family - Alzheimer's is a terrible disease and I too want to see it treatable as soon as possible, but in this case, if the data is inconclusive, then the drug is not actually a treatment for the disease, that's the point. The purpose of all the trials and tests is to ensure that a) the drug actually does what the scientists in the cutting-edge labs think it does, and b) that it's safe or at least has manageable side-effects.

I have a relative with this disease so I understand the drive to find a cure but it helps no-one to push through a drug that may end up causing more damage.

What could be benefited by not approving it with all the pertinent disclaimers about effectiveness?

And to turn it around, what harm would it cause society if it’s not approved due to inconclusive evidence and helps only some people? (Assuming no hard side effects)

Keep in mind, there are already ineffective treatments that sell hope and don’t help.

The drug has significant side effects, likely with more to be recognized in wider use — especially in combination with other people.

There is a massive cost, which will be paid directly by patients (creating financial stress & conflicting with other care needs) and indirectly by insurance providers who will cut corners and raise costs for everyone.

There is a psychological cost to telling people to take on all of the previous costs for something you know won’t have any benefit. Offering false hope isn’t a kindness.

Caveat: I'm not medically or pharmaceutically qualified

> What could be benefited by not approving it with all the pertinent disclaimers about effectiveness?

It prevents the drug being prescribed (at great cost!) to people who are desperate to try anything.

What would be the benefit of approving such a drug? Who is missing out by not being able to take a drug not known to be effective? I would consider it malpractice to be prescribed something not demonstrated to have a measurable positive effect. The human body is vastly complicated - we shouldn't mess with it without good reason.

> And to turn it around, what harm would it cause society if it’s not approved due to inconclusive evidence and helps only some people? (Assuming no hard side effects)

If it's not approved, then I would argue no harm comes to society. What harm is done if a drug that wasn't available before, still is not? Nothing has changed.

> Keep in mind, there are already ineffective treatments that sell hope and don’t help.

Absolutely, and they are, in my opinion, a work of evil. But the crucial difference is that such treatments (I'm assuming you're referring to quackery such as homeopathy) contain no active ingredient. That's why they aren't regulated. They can't cause medical harm because they don't do anything.

The biggest harm is going to be people getting side effects with no benefits. I suppose you could argue that Alzheimer's is so bad that who cares about bad side effects, but usually you would not want a drug on the market with no real benefit and a bunch of potential side effects sitting out there.

"What could be benefited by not approving it with all the pertinent disclaimers about effectiveness?"

Let's say it is approved, with all pertinent disclaimers. And that it has no side effects (which seems unlikely).

With little evidence of effectiveness, insurance, public or private, will not pay for it. They have every right, and at least a fiduciary responsibility not to.

But you are desperate, and you are willing to pay $130/day for the drug. What happens if it doesn't work? (As you say, the list of things that don't work is extensive.) Are you going to post on the net, "Our mother's medication didn't work and literally bankrupted us, but it's our fault"?

> I can walk 5 minutes down the block and buy an eight ball of fentanyl from a guy named TJ

I think TJ might be yanking your chain. "An eight ball" refers explicitly to 1/8 ounce of cocaine.

There would be approximately 35,000 doses of fentanyl in an eighth of the stuff.

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.

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.

That's incorrect. Biogen can't legally sell you the drug unless it's been approved by the FDA or they use one of the specific exemptions like doing a drug trial.

Why should Biogen be able to sell their drug? It hasn't been shown to work, it is for all intents and purposes at this point in time, snake oil.

Should Biogen be able to continue research and studies, sure, but they shouldn't be able to sell it until they have proof that it actually improves someone's life instead of having some effects on a possible bio-marker.

That's incorrect.

Doctors can (and do) prescribe drugs for off label usages. There's nothing "illegal" about it.

The reason they don't do that more commonly is malpractice lawsuits and insurance companies don't like to cover off label prescriptions.

An excellent example of this: Medical Marijuana. Not FDA approved for almost anything and the only reason it's "illegal" is because of federal DEA classification.

So long as it's not listed as having any therapeutic effects, you can fairly freely buy any non-controlled substance.

For example: https://www.amazon.com/Arsenic-99-9999-Crystalline-Metalloid...

Hang on, so I could totally sell off-patent insulin in America if I wanted to with a “not for therapeutic use” label? How do all those people keeping dying “because they couldn’t afford insulin” then? Feels like someone would capture the cheap end.

Yes, you could.

The issue is getting that off label insulin distributed. Insulin must be refrigerated which really makes distribution difficult. A pharmacy isn't going to store it in their refrigerators and stores aren't going to plop it down next to the milk.

Then, of course, you run into the risk that you get sued anyways by current insulin manufacturers for patent violations (good luck with that!).

Oh, and you also run the risk that someone takes your insulin and sues you for a bad reaction. With FDA approval, there's a much lower legal risk.

And finally, after you setup your insulin product, you simply run the risk that nobody uses it because it's off label and their doctors didn't prescribe it.

Oh, and for certain, your insurance will not cover it at all. So, bunch of risks with minimal rewards. Still completely legal. Can be done doesn't mean will be done.

Insulin is a FDA approved substance with therapeutic properties. How you label it is irrelevant.

You can't sell heroin with a "nutritional supplement"label either.

If a substance has no classification(neither controlled nor therapeutic) however, like water for example; you're free to sell it, to treat dehydration, or put a homeopathy label on it and sell it to cure cancer if you prefer.

lol. You can't order aducanumab on Amazon. The only place it exists in inside Biogen. There's no "off label" here.

Right, but that's not the point. The point is you are claiming that it'd be "illegal" for biogen to sell it. It's not because it's not a controlled substance.

Biogen won't sell it, but that has little to do with the legality of selling it and everything to do with the fact that they want insurance money and to market this.

That's not how that works. If Biogen tried to sell unlabelled bottles of aducanumab, the FDA would come after them in a heartbeat.

Picture the judge in the court case: "So, you developed this new molecule that never existed before, spent years testing it to treat alzheimer's, there's been hundreds of news stories about it, there is no other reason a consumer would buy it, and it costs $50k, but you expect the court to believe you didn't think it was being sold as a treatment?"

Might I again refer you to the fact that you can literally buy arsenic on Amazon.

Would they do it? No. Would it be risky? Yes. Would it be illegal? No.

> The only place it exists in inside Biogen.

You would order it from a compounding pharmacy, would would then do a custom synthesis for you. Or else just make it yourself in your basement.

doesn't this translate into a many year long permission to sell a drug with no evidence that it works?

It certainly sounds like it, yes.

There is inconclusive evidence that it works.

That's in theory a good scenario for allowing some level of use.

If this practical level of use is good, I don't know.

Given the costs, I don't think this is good enough. Medicare cannot afford to subsidize things are inconclusive especially given how 6 million Americans have Alzheiemrs.

The $50k/year above times 6 million is $300B. For $300,000,000,000, I suspect no one cares whether it works.

What do you mean by this? That sounds like a lot of money and I would think taxpayers would care if such a large amount were to be essentially thrown away.

I think a sane system would be where a drug is legal to use, and Medicare can decide it's not worth paying for.

Those should be be independent decisions.

> 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.

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.

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.

That's true, but I don't really see why the drug companies shouldn't pay those costs.

The second order effects may be that they wouldn't want to even try to develop a drug.

What world do you want to live in? (Rhetorical)

The third order effects may be continued erosion of respect for the federal government's regulatory process. Tread carefully. (And make lots of money while you can.)

And blowing out the drug budget for medicare for a very expensive but futile treatment.

If you say they should pay the costs, they should also reap the rewards, so in that case you have to accept that drugs are really expensive.

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.

And by "can distribute it", do they mean sell? 'Cause selling something you have no reason to believe is fit for purpose can cause problems.

That is, unless a large government agency has you back.

> if a patient and her doctor believe this is the best treatment, the FDA shouldn't prevent them from getting access to it.

I question whether a patient or her doctor is more qualified to make that call than a panel of experts. But we already allow drug trials - those are just measured. And if there are no other treatments, the FDA has had a compassionate use protocol for a long time to let people attempt anything over nothing.

And if the doctor is getting kickbacks?

I was prescribed a very expensive new drug that I couldn’t tolerate. Eliquis, Xarelto.

Medical office went to absurd lengths to keep me on it rather then switching to a cheaper alternative. Too multiple ER visits to get them to switch.

   Kept calling me a liar for saying it had side effects.

Realized later that they probably made money off it. Would love to know if true.

> Realized later that they probably made money off it. Would love to know if true.

They probably didn't even make a lot of money. Although they paid $18.3 million to doctors in 2018, only nine doctors got over $100k.

Are you in the US? By law, there has been a public database of all pharama dollars to doctors for a bit over a decade. It covers lunches and consulting fees and such. For 2018, ProPublica has a searchable database. Here's Xarelto's results.

Edit: I just realized I forgot to paste in the link. I hope I edit this before you see it: https://projects.propublica.org/docdollars/products/16510

One place to search https://projects.propublica.org/docdollars/.

Disclaimer: not familiar with US medical industry or incentives schemes for docs

> No need for anyone to wear a mask.

-- Many panels of experts in Feb 2020.

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.

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.

HCQ and ivermectin efficacy agaist SARS-CoV-2 was suppressed early on. If there were existing effective therapeutics, then emergency use authorization for the vaccines would not have been legally permissible (in the US).

Is India in on it, too? https://www.tribuneindia.com/news/nation/new-treatment-guide...

In all honesty, do you consider yourself a rational person? As in, is there something that could actually convince you that those drugs don't do much for Covid? I ask with absolute sincerity.

> Ivermectin

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.

We shouldn't tie approval to effectiveness, it should only be about harm. Effectiveness claims can be verified through other approaches.

Why should my insurance premiums go up to pay for people getting ineffective treatments? These drugs aren't exactly charity, at $56k/year that's a good chunk of change for something not proven to work.

Excellent point: why should your insurance have to cover every FDA-approved drug, and regardless of cost?

My guess is your insurance doesn’t cover every approved treatment. But if it does, is that a problem with the FDA (which regulates drugs), or with your insurance policy (which decides how to pay for them)? I’d suggest your complaints about insurance costs are more closely tied to the latter.

> why should your insurance have to cover every FDA-approved drug, and regardless of cost?

If only there was some group of experts that decided that some drugs were safe and effective vs. not. We could even make it a nonprofit group to avoid conflicts. Heck, we could get the federal government to fund and and even pass a law that gave their recommendations teeth.

Just remember the FDA denies people who are dying the ability to choose their treatment.

No, the FDA doesn't deny people who are dying the ability to choose their treatment. What nonsense is this? There used to be requirements to document the treatment, but even that went away.

Or do you mean in the cases where there are already treatments? Because, yes, then take medicine not Dr. Mike's Magic Tonic.

You have scabies? Asthma? Cancer?

Well, now, have I got something for you! Just right here, in this bottle, I have a medication that is not only federally guaranteed not to hurt you, but also will fix your problem right up! And it's just $10,000 per bottle! Step right up!

Worse than that. A drain on public resources for something that does not work. This drug is very expensive.

They moved forward with a different type of approval specifically meant to mitigate the false hope you are speaking of. I don't see the mutual exclusivity here.

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.

So, do you think people should be allowed to take ivermectin and "that drug" (the one that rhymes with mydoxyborofin) for COVID-19 if they want to, given that both of those have been studied for years and are known to have very little side effects?

No, the patents on these have expired and nobody will make any money if we promote them. Also it would have been near impossible to get emergency use authorisation for these vaccines if we had at all listened to the science on these.

You won't even say the name of the drug hydroxychloroquine? Trump really did a number on you!

head explodes

I agree. The FDA should be a watch dog group that provides us with the knowledge to make our own decisions. How many people have died because a drug took too long or never made it to get approved?

I agree. And regardless of where you stand on the issue, the current regulations with regards to off-label usage are totally inconsistent. Doctors are perfectly free to prescribe drugs for conditions that are completely unrelated to the what they were approved for.

Drug X is proven safe but not proven effective. It's illegal to use to treat condition Q under any circumstances. Drug Y is proven safe, proven effective for condition M. It's perfectly legal to use for unrelated condition Q. How does this make any sense?

Because it cuts economic incentive to produce ineffective (but safe) drugs on purpose.

Maybe, but it’s not clear to me that the FDA is (or should be) experts in weighing economic incentives for good behavior. There’s plenty of bad economic incentives created by the current FDA process; just ask the Lovaza guys, charging a 10x markup for fish oil. In an ideal world, I don’t think the FDA should have any role in drug approvals other than preventing direct medical harm.

This would likely lead to a pharmaceutical landscape that is more like the supplements industry -- no thank you.

That's not really relevant here.

Safe drugs can be sold OTC with all the homeopathics. FDA approval here is about fraudulent claims of effectiveness.

You argue that unsafe drugs should be available for sale too, but that's not what happened here and IMO it ignores the societal risks of unsafe things floating around were they can harm non-consenting people, as well as the rights of people who want to be free from transient temptation to make irrevocable decisions.

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?

Sure, but the doctor doesn't have to do much research in this case. This is front-page news in the NY Times. And about "every single medication": this is the only approved medication to delay clinical decline due to Alzheimer's. And there are only a few medications to treat symptoms.

I know this isn't a perfect world, but it doesn't seem to be asking a lot for a doctor to know this. (Especially for a drug that currently costs $56K/year and presumably will cost more next year.)

You seem to have an incredibly optimistic view of the both the medical profession and human attention span.

Isn't it fraud to sell an Alzheimer's drug that doesn't prevent Alzheimer's?

Only if you make untrue claims. If you claim only what is proven, then it is not fraud.

> ADUHELM is an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease.

- https://www.biogencdn.com/us/aduhelm-pi.pdf

I believe the advisory panel's position is that it is not indicated for the treatment of Alzheimer's and that Biogen should not be allowed to say this.

In their press release (https://investors.biogen.com/news-releases/news-release-deta...), they explicitly describe it as an "Alzheimer's disease treatment". Again, I think the advisory panel considers this untrue, and certainly unproven.

The FDA could have said "this drug is safe and may be sold, but you may not describe it as an Alzheimer's treatment, and you must explicitly state that it has been found to be ineffective as an Alzheimer's treatment in clinical trials".

So how is Biogen going to get doctors to prescribe and people to pay $50K for a drug with no brand recognition nor eligibility for insurance, and no claims of actual effectiveness?

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.

None of this vision would work for a variety of reasons, but the biggest one is that insurance companies are not going to agree to pay for medications that are not proven effective.

Your personal freedom to try whichever medications you want would be limited unless you are willing to pay out of pocket for everything.

As I understand it the issue is

* Currently the US welfare agencies will provide ~any FDA-approved drug for someone with the illness for which the drug was approved

* In this case, they probably won't - in the worst case scenario it would double their spending on prescription drugs and seems unlikely to help anyone

* So this is going to sever the link between FDA approval and medicaid spending.

* Now you have an awkward situation where agencies that not really equipped to make judgements on dug effectiveness, and which are not insulated from politics, have to make those decisions.

This could all work out for the best in the long term but may also be very awkward in the short term.

Wouldn't charging $56k / year for a drug that not only doesn't work, but has a high chance to induce brain swelling be considered fraud?

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.

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.

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.

Yes, and the TSA is required to check the shoes of all passengers who want to fly because of this: https://en.wikipedia.org/wiki/Richard_Reid

The fact the people who make a policy have a specific thing they want to achieve with that policy does not automatically make it a good policy. That remains true even if the thing they want to prevent is bad and could kill people.

I met one of the thalidomide babies once, he was a PI for a research project I worked on. He was a relatively tall man, and had tiny arms that would have looked fine on a 2 year old.

Stopping stuff like that seems like a reasonable thing for the FDA to do, even at the cost of it taking longer to approve drugs.

> even at the cost of it taking longer to approve drugs.

"Taking longer to approve drugs" can be restated as "forbidding the use of potential treatments for longer". To the extent that those treatments work better than the next-best option, delaying approval is effectively forcing the worse treatment on everyone who would have switched for the duration of the delay. If there is no alternative treatment, delaying approval is effectively equivalent to forcing the people affected by a disease to just live with that disease for the duration of the delay.

Picking pretty much at random from stuff recently approved by the FDA, we find that Ocrelizumab, a drug to treat multiple sclerosis (MS), was approved in 2017. Patients treated with Ocrelizumab have just over half the chance of developing symptoms bad enough to require a walking aid (4.2% vs 7.3%) as compared to the next-best treatment (interferon beta-1a) over 96 weeks.

Phase III clinical trials of Ocrelizumab started in March of 2011, and completed in July of 2015. In October 2015, Genentech presented the results of the phase III trials to the FDA. The FDA recognized how important this treatment was, and gave it breakthrough therapy designation, fast track designation, and priority review. It was approved for use in March of 2017.

That is uncommonly fast for the FDA, but even so it took them a year and a half to "move fast" on this treatment. Let's be generous and say that determining that the phase III results were not literally fraudulent takes fully 6 months -- that means that in the case of this particular drug, the FDA only delayed approval for a single year. About 150,000 people take Ocrelizumab worldwide, most of which are probably in the US.

As such, the FDA's (much shorter than usual) delay for this particular drug "only" cost about 2,500 people the ability to walk unaided.

How many delays like this does it take before we decide that the cure (delaying effective treatments for nasty diseases) is worse than the disease (occasionally letting through a medication with extremely nasty side effects)?

This isn't a rhetorical question by the way. My personal answer is probably somewhere in the ballpark of "aim for a 1:1 ratio of QALYs lost to drugs that were approved and shouldn't have been : QALYs lost to drugs that should have been approved and weren't". Maybe 1:5, if we think harm from inaction isn't quite as bad as harm from action. But my best ballpark guess for the actual ratio the FDA is achieving is probably more like 1:100 or 1:1000, and I don't find that even remotely reasonable.

(Note that this entirely ignores the question of whether the current FDA does even have the benefit of delaying / not approving stuff that doesn't work, which is the subject of another rather active discussion on HN today: https://news.ycombinator.com/item?id=27472107).

> 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.

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.

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.

Agreed, it is not to be expected that a doctor is able to follow the scientific literature for hundreds of different topics. However, I would expect a specialist to know their field well enough to assist a patient/guardian in making a somewhat informed decision.

I take your point that companies can falsely advertise their products. I think there is a place for a government body to make sure claims about healthcare products are factual. In this particular case we are talking about a drug that appears to not cause any harm. So I don’t see any reason to prevent an adult to make a decision with the help of a physician to administer said drug.

> I take your point that companies can falsely advertise their products. I think there is a place for a government body to make sure claims about healthcare products are factual.

The problem is that deciding whether something is factual is a lot easier for simple things. For something like this, there are vaguer connections between facts like plaque removal and more nebulous things like meaningful outcomes for patients.

> In this particular case we are talking about a drug that appears to not cause any harm.

Other than brain swelling or bleeding, headache, falling, diarrhea, and confusion, delirium or disorientation, you mean?

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.

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.

Efficacy and safety are intertwined. Safety can sometimes only be evaluated in the context of efficacy. For example, you wouldn't amputate a healthy arm. But for a gangrenous one, it may be the only option.

For establishing efficacy and safety, trials are the only process that works. Nobody can predict the effects of drugs because the current understanding of biology is very incomplete.

Thalidomide [1] shows the wisdom of the current approach.

[1]: https://en.m.wikipedia.org/wiki/Thalidomide

> These are extraordinarily complex choices that seldom have a right answer for all possible patients.

I think "is there any evidence that this drug actually works" can a remarkably simple decision, given the results of clinical trials.

The fact that desperate people may be willing to blow tens of thousands of dollars on something that doesn't work, doesn't make it more complex.

> I don't believe that screening drugs based on effectiveness is a proper role for any government agency...Better would be for the only role of the FDA in decisions like this to be determining if the manufacturer is making fraudulent claims.

I think you come in with wrong assumptions. The FDA has little to no authority when it comes to off-label uses — doctors have a lot of leeway to prescribe drugs for whatever non-approved use they judge to be effective.

So the FDA's role already is intertwined with marketing. A doctor can today prescribe Viagra as a treatment to Alzheimers, but it would be illegal for Pfizer to market Viagra for treating Alzheimers until it gets FDA approval for that specific use.

> 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).

I suppose there is some fine ethical reasoning that would distinguish between selling something that you know not to work and selling something that you don't know won't work.

Of course, financially incentivizing ignorance is probably not the best precedent.

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.

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.

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.

I don’t see what’s wrong with the FDA approving a drug only for specific niche proximate-cause X that currently has absolutely no reason to ever be prescribed, presuming it’s disallowed from being marketed as being “for” anything other than specific niche proximate-cause X. Maybe someday a problem will come along that can be solved by treating for specific niche proximate-cause X — and hey, then you’ve already got an approved drug to treat that problem. (For example, maybe in this case the drug could also happen to treat some novel prion disease, where the mechanism of that prion disease involves beta-amyloid buildup, such that this drug would actually stop that disease’s progression. Sort of the same way corticosterioids were already approved for other uses, but then happened to be able to be used in managing COVID, because the same mechanism they target — systemic inflammation — was being triggered by the disease.)

Of course, if the marketability restrictions truly worked the way I’m talking about, then the drug would have zero sales until that real-world problem matching its niche use-case came along. Which means there’d be no point in manufacturing it until then. But it’d be nice that it’d be “on the books” as being allowed to be produced and sold, such that it could be later rushed to market if the problem it solves was ever realized as a necessary problem to solve.

As someone else commented above - there is precendent to this, this is exactly how the HIV epidemic was approached. I was as upset about this decision as everyone else on this thread, then I read this[0] and now maybe not so much.

[0] https://forum.quartertothree.com/t/wtf-is-going-on-at-the-fd...

I'm impressed with the information and detailed discussions about this topic from a gaming forum...

This has historically been a challenge regarding understanding the mechanisms of Alzheimer's in the first place, let alone treating the disease.

We know the plaques and the memory dysfunction are correlated. But we don't know whether the plaques are build up of waste product from the mechanism that is destroying memory function or the cause of the memory function loss. If it's merely a waste product, clearing it out of the brain may not only have no effect on the memory loss, it could even accelerate it (if the chemistry of the process is such that build up of plaques interferes with whatever process damages memory). Destroying the plaques may be like picking a scab off a wound.

Biomedicine is hard; none of the systems operate in isolation and everything is intertwined.

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.

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.

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?

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

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

"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?

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.

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