funky-data/E+ via Getty Images
funky-data/E+ via Getty Images
Two years ago, I wrote here about a new drug that was up for approval for ALS patients (who sadly have very few therapeutic options at all). The drug (Relyvrio, a mixture of sodium phenylbutyrate and taurursodiol) had been put through a Phase II trial by its developer (Amylyx), but as you'll see from that earlier post and the references therein, the data were not compelling. There were a number of statistical problems with the trial, and even as presented, it barely made the case for efficacy. When the FDA's own statisticians tried to correct for the gaps in the data, it seemed to make the readout worse every time. An uncharitable view would be that Amylyx (NASDAQ:AMLX) ended up presenting the clinical package from the only angle that made it even possible to believe that the drug worked, and the FDA advisory committee ended up voting against approval.
But as you'll see from this timeline, that wasn't the end of the story. 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. The drug has been selling well, above investor expectations. In a paper published in December, post-hoc analysis of phase II (137 patients) suggested lowering of biomarkers of inflammation. So...
You know what's coming. The Phase III trial has just read out, and Relyvrio shows no hint of actually working. Not against the primary endpoint (improvement on an ALS functional rating scale, versus placebo), nor against any of the secondary ones (patient self-reports, respiratory function, overall survival, etc.) This drug doesn't work, and it never did. It did have a very good safety profile, fortunately, so it seems unlikely that anyone was physically harmed by it over the last year and a half. But ALS patients (or their insurance companies) had the chance to pay for a drug ($158,000/yr list, who knows what the real price was somewhere below that) for what is in the end a combination of two generic medicines. And they might as well have been given peppermint candy for all the good it did. Amylyx says that they will announce their plans for the drug in the coming weeks, but what plans can those possibly be? Which landfill to take it to?
Just like with the recent approvals in Alzheimer's, the 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. Congratulations? I hate to be this way, but I continue to believe that unmet medical need is not by itself enough reason to approve a drug. You need what you've always needed: efficacy and safety. Boring, tedious, expensive efficacy and safety. Desire and despair don't figure in much - in a much different universe, one whose physical laws respected and validated human emotions and human suffering, they would. But we don't live in that world. We never have.
Postscript: Also in today's news, a surprising development - the FDA has announced that they are going to convene an advisory panel for Lilly's (LLY) new Alzheimer's antibody donanemab. Many had expected it to be approved shortly, so this is pretty unexpected. But unless the FDA has decided to have a major change of heart (or a major change of head, depending on how you look at it), they're going to approve it, no matter what the advisory committee says. Isn't that how it works in the modern era?
Disclosure: None
Editor's Note: The summary bullets for this article were chosen by Seeking Alpha editors.