Amylyx Sheds More Light on Relyvrio’s Late-Stage Trial Failure in ALS

ALS Neuron_iStock, Dr_Microbe

Pictured: 3D illustration of nerve cells being destroyed/iStock, Dr_Microbe

Amylyx Pharmaceuticals on Tuesday unveiled more data from the Phase III PHOENIX study, providing additional context on the recently announced failure of its now-withdrawn amyotrophic lateral sclerosis drug Relyvrio (sodium phenylbutyrate and taurursodiol).

Amylyx first announced that Relyvrio failed the Phase III PHOENIX trial in March 2024, though the company did not reveal specific data from the trial then. The data presented on Tuesday at the 2024 American Academy of Neurology (AAN24) annual meeting showed that at 48 weeks patients who received Relyvrio saw a 14.98-point drop in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), a validated tool that measures the severity of amyotrophic lateral sclerosis (ALS) including the progression of disability and respiratory impairment.

In the late-stage trial, those patients in the placebo arm saw a 15.32-point decrease in scores from baseline. The resulting treatment effect was 0.343, which was in favor of Relyvrio, though not significantly with a p-value of 0.667.

Relyvrio also failed its secondary endpoints. After 48 weeks of follow-up, Amylyx’s drug outperformed placebo by 2.02 points in terms of slow vital capacity and by 1.41 points in the Amyotrophic Lateral Sclerosis Assessment Questionnaire. Both treatment effects fell short of statistical significance. Subgroup analyses likewise did not spot signals of significant efficacy.

As of the AAN24 annual meeting, overall survival data had not yet matured, according to Amylyx. PHOENIX will continue to collect data in this regard.

Amylyx co-CEO Joshua Cohen told Endpoints News that the company is still trying to figure out what caused the failure. “Might there be certain biomarkers, might there be certain biological differences, or otherwise? Or is it just statistical chance? I think all of those are possibilities and things we want to keep learning more about.”

Relyvrio is a combination of two compounds: sodium phenylbutyrate and taurursodiol. Its exact mechanism is still unknown but it is believed to reduce endoplasmic reticulum stress and mitochondrial dysfunction, improving cellular function and lowering cell death. The FDA approved Relyvrio in September 2022.

Prior to Relyvrio’s approval, Cohen and co-CEO Justin Klee pledged that Amylyx would pull the drug from the market if its late-stage results fell flat. “The commitment we made at the advisory committee meeting is we’ll do what’s right for patients,” Klee said at the time.

The CEOs made good on their promise earlier this month, when they voluntarily withdrew Relyvrio from the U.S. and Canadian markets. Reeling from the failure of PHOENIX, Amylyx also instituted a sweeping restructuring plan that saw 70% of its workforce laid off.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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