Amylyx Pharmaceuticals has decided to withdraw its amyotrophic lateral sclerosis (ALS) drug, Relyvrio, from the market after it failed to meet the primary and secondary endpoints in its phase 3 trial. The trial intended to confirm the efficacy of Relyvrio in improving physical function in ALS patients as measured by the revised ALS functional rating scale. The candidate’s failure led Amylyx to reduce its workforce by some 70%. This outcome marks a significant setback for ALS treatment - a field already limited in effective therapeutic options. Amylyx plans to continue exploring the drug's potential for other neurodegenerative diseases and is pursuing a new clinical trial for a different ALS treatment.

The following article originally appeared in Fierce Pharma.

Amylyx Pharmaceuticals is keeping a promise by pulling the amyotrophic lateral sclerosis (ALS) therapy Relyvrio off the market after the drug failed in a confirmatory trial.

Thursday’s announcement was largely expected after the company last month revealed that Relyvrio came up short across the primary and secondary endpoints of the phase 3 PHOENIX trial. In the study, the drug failed to beat placebo at improving patients’ physical function on the revised ALS functional rating scale, a key measurement of clinical benefit.

Although Amylyx’s co-CEO Justin Klee didn’t immediately announce a commercial decision after the study readout, industry watchers figured that the withdrawal would follow given how completely the drug had failed. Previously, Klee promised to voluntarily remove Relyvrio from the market if PHOENIX were not successful. That pledge helped persuade an FDA advisory committee to support the drug in 2022 after a prior rejection.

Relyvrio’s trial fail and subsequent market withdrawal are serious setbacks to the ALS field, where there are few options to treat the fatal neurodegenerative disease that affects motor neurons.

Besides Relyvrio, the FDA has approved Mitsubishi Tanabe Pharma’s antioxidant drug Radicava and different formulations of an old drug called riluzole, which has shown limited efficacy, to treat ALS. Biogen and Ionis Pharmaceuticals’ Qalsody also has an accelerated approval, but only for a small subtype of ALS patients with a mutation in the SOD1 gene. The antisense drug previously failed in a phase 3 trial in patients who had shown ALS-related muscle weakness, and Biogen is running another phase 3 in pre-symptomatic patients.

In September, another FDA advisory committee voted against an ALS cell therapy made by BrainStorm Cell Therapeutics, saying the candidate didn’t have enough evidence to show it’s effective at slowing the progression of mild to moderate ALS. In February, Sanofi and its partner Denali Therapeutics said their RIPK1 inhibitor program had failed in a phase 2 trial in ALS.

The lack of treatment options led to a wave of support for Relyvrio from the ALS community, which played a major role in the positive vote from the FDA's advisory panel and an eventual U.S. approval in 2022.

Across the pond, drug reviewers at the European Medicines Agency in October 2023 confirmed their rejection of the drug under the brand name Albrioza after Amylyx had appealed a previous negative opinion.

Between the U.S. and Canada, Relyvrio brought in $381 million in revenue in 2023. The market withdrawal applies to both the U.S. and Canada. The drug will no longer be available for new patients starting Thursday, and existing patients may choose to switch to a free drug program.

Relyvrio’s flop deals a major blow to Amylyx and its employees. As its sole source of revenue is gone, the Massachusetts biotech will lay off about 70% of its workforce to focus financial resources on some upcoming clinical milestones, the company said Thursday.

As of the end of 2023, Amylyx had 384 full-time employees, according to its annual securities filing. The job cuts will leave the company with about 100 remaining staffers.

But Amylyx isn’t giving up on the drug, coded as AMX0035, altogether. The company is still running a phase 3 trial dubbed ORION for the drug in progressive supranuclear palsy, with a readout now expected around mid-2025.

Interim data from the phase 2 HELIOS study in Wolfram syndrome will be shared April 10, Amylyx said Thursday.

Wolfram is another neurodegenerative disease, which is marked by childhood onset of diabetes, vision loss and other neurological problems. During a February interview with Fierce Pharma, Klee noted that because Wolfram is an ultrarare disease, the company may pursue a different regulatory path than in ALS. HELIOS is the first interventional study in the disease setting, he noted.

Back to ALS, Amylyx is planning to initiate a trial on AMX0114, a clinical antisense oligonucleotide targeting calpain-2. In addition, results from Relyvrio’s failed trial will be shared during a presentation at the American Academy of Neurology annual meeting on April 16.

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