By The Numbers - part the fiftieth

One of the sore points against FDA is the power to approve drugs in a provisional manner. If small, early trials indicate that a compound does some good, then the compound is allowed on the market, and the company is required to run a full-blown post-approval trial. This trial is supposed to be run expeditiously, but not always so.

Here's the problem: that postmarketing study has never taken place. In fact, it hasn't even been started. (Edit: looks like they've finally gotten it off the ground since the CRL was issued).

Amylyx developed a drug for ALS under such a protocol, and has run such a trial. And the drug failed spectacularly. The existing, albeit somewhat arbitrary, standard for success in statistical studies is p-value of .05 or smaller. Has been so for decades. The drug pulled .67. Not in the ballpark? Not on the same continent.

I haven't done the digging, but such a result, once again, calls into question the value of FDA giving provisional approval to compounds.

Sarepta's DMD drugs, particularly its first, got provisional approval. The confirmatory studies have not been done expeditiously. And Sarepta used (created?) the tactic of inflaming the patient community to pressure FDA to approve.

Initially, the FDA wanted Amylyx to run another, larger study before submitting its drug for review. But after receiving intense backlash from ALS patients and advocates, who have pressed regulators to be more flexible in evaluating potential treatments, the agency backtracked. Amylyx was allowed to apply for approval while simultaneously running that additional trial.

Note that the EU regulator was not impressed with the initial trials, and didn't approve. I suspect there will be much discussion of the structure and conduct of those promising initial trials.