[entee]

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...

[abadaba]

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...

[entee]

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...