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.
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...
https://forum.quartertothree.com/t/wtf-is-going-on-at-the-fd...
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...
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.
Yes, improve your social relationships and cognitive health by joining a nunnery or monastery! https://en.wikipedia.org/wiki/Nun_Study
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.
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.
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.
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.
What world do you want to live in? (Rhetorical)
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.
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...
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.
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.
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.
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?"
Would they do it? No. Would it be risky? Yes. Would it be illegal? No.
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.
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 in theory a good scenario for allowing some level of use.
If this practical level of use is good, I don't know.
Those should be be independent decisions.
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.
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.
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
Disclaimer: not familiar with US medical industry or incentives schemes for docs
-- Many panels of experts in Feb 2020.
That is, unless a large government agency has you back.
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
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.
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.
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
> 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 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
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.
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!
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.
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.
Or do you mean in the cases where there are already treatments? Because, yes, then take medicine not Dr. Mike's Magic Tonic.
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.
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.
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.
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?
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.
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?"
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?
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.
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.
To approve the drug despite the lack of efficacy is unethical, especially considering there are potentially severe side effects like brain swelling.
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.
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.
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.
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"?
> 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.
> 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.
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.
Be well.
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.
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.