Amylyx plummets as confirmatory trial of ALS drug fails

Justin Klee and Joshua Cohen, co-CEOs of Amylyx Pharma

Justin Klee and Joshua Cohen, co-CEOs of Amylyx Pharma

Shares in Amylyx have cratered after the company reported a confirmatory trial of its amyotrophic lateral sclerosis (ALS) therapy Relyvrio missed all its objectives, putting its accelerated approval in jeopardy.

Relyvrio (sodium phenylbutyrate/taurursodiol), which has a list price of $158,000 per year in the US and is also sold in Canada as Albrioza, generated sales of about $381 million last year and is Amylyx’s only commercial product. Shares in the company lost more than 82% of their value after the news emerged.

It was cleared controversially by the FDA in 2022, after two years of wrangling between the company and regulator and debates around the drug’s efficacy, becoming only the third drug for ALS ever to be approved in the US after Mitsubishi Tanabe’s Radicava (edaravone) and generic drug riluzole, sold as Rilutek by Sanofi.

The approval was based on the phase 2 CENTAUR trial and post hoc data analysis, which failed to convince experts at a first FDA advisory committee meeting and - unusually - was considered at a second meeting, where it was recommended. There is now speculation that the new development could invite scrutiny of the FDA’s approach to accelerated approval of drugs with limited efficacy data.

In a statement, Amylyx said it would continue to make the drug available while it discusses the new data with regulators and the ALS community, but acknowledged that it may have to voluntarily withdraw it from the market.

If Relyvrio is pulled, Amylyx will have to switch its focus to its R&D pipeline headed by AMX0035 (based on the same active ingredients as Relyvrio) for the treatment of Wolfram syndrome and progressive supranuclear palsy (PSP). AMX0035 is in the phase 3 ORION study in PSP, with results due in 2025 or 2026, and a phase 2 study in Wolfram syndrome, with results due later this year. It also has a calpain-2-targeting antisense drug for ALS, AMX0114, in early development.

In the new PHOENIX trial, Relyvrio missed both the primary endpoint of change from baseline in the revised ALS functional rating scale (ALSFRS-R) total score at Week 48, as well as secondary endpoints that included quality of life patient-reported outcome (PRO) assessments, overall survival, and respiratory function as measured by slow vital capacity (SVC).

“We are surprised and deeply disappointed by the PHOENIX results following the positive data from the CENTAUR trial,” said Amylyx’s co-chief executives, Justin Klee and Joshua Cohen, in a statement.

“Our main priority at the moment is sharing the information with people living with ALS and their treating physicians; this is part of our continued commitment to them and our mission,” they added.