Amylyx Reveals Details of Relyvrio's ALS Trial Shortcomings

Amylyx Pharmaceuticals has recently shared additional data from its Phase III PHOENIX study, shedding more light on the unsuccessful outcome of its ALS drug, Relyvrio. Initially, the company declared the drug's failure in March 2024, but did not disclose specific trial details at that time. The latest findings, presented at the 2024 American Academy of Neurology (AAN24) conference, indicated that after 48 weeks of treatment, patients who took Relyvrio experienced a 14.98-point decline in the ALSFRS-R, a standard measure of ALS severity, including disability progression and respiratory issues.

In contrast, participants who received a placebo showed a 15.32-point decrease in their scores. The treatment effect was a modest 0.343 in favor of Relyvrio, but this was not statistically significant (p-value of 0.667). Relyvrio also missed its secondary goals, with only minor advantages over placebo in vital capacity and the ALS Assessment Questionnaire, neither of which reached statistical significance. Subgroup analyses did not yield significant efficacy signals either.

Amylyx noted that survival data was not yet conclusive at the time of the AAN24 meeting and that the PHOENIX study would continue to gather information on this aspect.

Joshua Cohen, co-CEO of Amylyx, expressed that the company is actively investigating the reasons behind the drug's failure, considering potential biomarkers, biological differences, or even statistical variance. Relyvrio is composed of sodium phenylbutyrate and taurursodiol, and while its precise mode of action is not fully understood, it is thought to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, potentially enhancing cell function and reducing cell death.

The FDA granted approval to Relyvrio in September 2022. Prior to this approval, Amylyx's leaders committed to removing the drug from the market if the late-stage trial results were not promising. True to their word, the company withdrew Relyvrio from the U.S. and Canadian markets following the PHOENIX trial's failure. In response to this setback, Amylyx also implemented a major restructuring, which included a reduction of its workforce by 70%.

Relyvrio's withdrawal and the subsequent restructuring highlight the challenges faced by pharmaceutical companies in developing effective treatments for ALS, a disease with a high unmet medical need. The search for a successful therapy continues, with researchers and companies exploring various approaches to combat this debilitating condition.