08 Mar 2024

Enticing a reluctant FDA Advisory Committee to greenlight its drug based solely on Phase 2, Amylyx Pharmaceuticals promised, sort of, that if its ongoing Phase 3 trial returned negative results, it would voluntarily withdraw the drug. Those results are now in hand.

On March 8, the company announced that its Phase 3 PHOENIX trial had failed to meet its primary endpoint (press release). In the global, year-long study of 664 ALS patients, Relyvrio did not slow disease progression compared to placebo. The p value on the primary endpoint was 0.667. Secondary endpoints measuring quality of life and muscle function were also uniformly negative.

According to the press release, Amylyx will decide on Relyvrio’s fate in the next two months. In the meantime, the company will pause promotion, but continue to provide the drug and patient support services to current users. An open-label extension to the trial continues in Europe, as do separate studies in Wolfram syndrome and Progressive Supranuclear Palsy.

The FDA approved Relyvrio in 2022, based on data from a Phase 2 trial with 137 patients. In that study, Relyvrio was reported to slow decline by about a quarter on the ALS Functional Rating Scale-Revised (September 2020 news). The advisory committee initially voted against approval, citing insufficient evidence of benefit. In a controversial move, and after pressure from outside groups, the committee reconvened, and reversed course. The drug, a combination of sodium phenylbutyrate and taurursodiol, debuted with a list price of $158,000 per year, while the Phase 3 was ongoing (October 2022 news).

The trial failure dooms Relyvrio’s conditional approval in Canada, where it has been marketed as Albrioza. The drug was rejected previously in the European Union.—Pat McCaffrey