Amylyx’s chances rest on a knife edge

Negative, but not as negative as many had been expecting; this was the conclusion from yesterday’s adcom discussing Amylyx’s amyotrophic lateral sclerosis project AMX0035. Panellists voted 6-4 that efficacy had not been established, something that would normally point to an FDA rejection. However, after the controversial approval of another CNS drug, Biogen’s Aduhelm, also following a negative panel vote, the outcome for AMX0035 is anybody’s guess. Perhaps the FDA will be swayed by yesterday’s patient testimonies, and advocacy groups will no doubt keep up the pressure to approve AMX0035. It is also noteworthy that, amid questions about the statistical rigour of Amylyx’s phase 2 Centaur study, one vote in favour of the project came from the panel’s biostatistician, Dean Follmann. Evercore ISI’s Umer Raffat raised the possibility of accelerated approval, which was not discussed at yesterday’s adcom. While there is a lack of surrogate endpoints in ALS, Amylyx's phase 3 trial, Phoenix, is already under way – perhaps opening the door for a conditional approval with later confirmation if the trial is positive. Whichever way the FDA comes down, one thing is certain: Amylyx investors face a nervous wait before AMX0035’s June 29 Pdufa date.