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Comment by dddddaviddddd | Hacker News Reader

> The Phase III trial has just read out, and Relyvrio shows no hint of actually working.... It did have a very good safety profile, fortunately, so it seems unlikely that anyone was physically harmed.

Phase II trials are more about safety than efficacy, so I'd say the system worked as designed.

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The problem is not the trial. The problem was an out of order early approval after only a phase two trial with very weak evidence. The phase three trial of course would go on even without such an out-of-order approval. The false hope such an approval creates doesn’t just affect patients directly. It may lead other companies to abandon or slow down therapies that might have competed in this indication. Approval of a drug is a huge deal. Perhaps eventually our drug approval system will change, but right now approval gives a company the power to market a drug to doctors, and doctors can prescribe it to patients, patients can ask for it, insurers cover it, and so on… This one was a conditional approval and the condition failed, which means the system still works, however it now has a possible loophole for how to bootstrap a pharma company. It is not clear yet if that loophole may increase human suffering on average, or not, and it likely depends on how the companies that take advantage of such a loophole grow. Drug discovery, design, and development are capital intensive operations and suffer from lack of innovation, but they also attract greedy people at the executive level who don’t bring therapeutic innovations to the table but rather find out how to draw investor money.

No, phase 2 is absolutely about efficacy.

One wonders how they got as far as Phase III trials without actually working.

Final 'graph of the article:

[T]he patient advocacy groups took victory laps after Relyvrio was approved, and they were a big part of the pressure that made the FDA reverse its initial correct decision.

Motivated reasoning, whether by commercial interests, patient advocates, or any other group, is inimical with truth-finding.

Though on the grounds of potential benefit vs. known harm (which is assessed in Phase I/II trials) and partial knowledge, a provisional approval in the case of a treatment for a chronic, progressive, and fatal condition is reasonably defensible. The FDA's conditional approval was based on Phase III trials showing efficacy. The dice were rolled, though the gamble in this case proved fruitless.

ALSA ALS association funded AMX0035 (previous name of Relyvrio) and by contract would get up to 3.3 $M if the drug was successful:

https://secure2.convio.net/alsa/site/SPageNavigator/blog_090...

Phase III is when you test efficacy so it’s exactly how it’s meant to be

In this case, the FDA had approved the drug, though conditionally.

Second 'graph of TFA:

A second advisory committee meeting was convened, and if that phrase sounds odd to you, it should. That's a very unusual thing to do. This one voted for approval, and the FDA did approve the drug in September of 2022. There was a condition, though: Amylyx was already working on a Phase III trial, and they committed to withdrawing the drug if this trial showed no efficacy.

considering costs this doesn't sound very utilitarian

Why would you test something for efficacy before you're sure it's safe? You'll end up testing a bunch of harmful substances that don't actually do anything.

Maybe because the real standard is "the benefits out weigh the risks" you might want a drug that has a 10% chance of harm if it has a 90% chance of benefit, for a condition that is terminal if untreated.

Fair point, although it also seems nonsensical to test safety for human consumption before having a robust hypothesis for desired effects.

It's not true that safety is fast and easy to check.

Is there utility in knowing the lethal dose of a drug before you administer an efficacy study. Libertarians wonder…

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