AMX0035—approved as Relyvrio in 2022 for amyotrophic lateral sclerosis but voluntarily pulled from the market last year—was unable to distinguish itself from placebo in a mid-to-late-stage trial of progressive supranuclear palsy.
Amylyx Pharmaceuticals is halting clinical development of AMX0035 in progressive supranuclear palsy, a rare neurodegenerative disease.
This discontinuation, announced Wednesday, comes after AMX0035 failed to significantly distinguish itself from placebo in the Phase IIb/III ORION trial at a 24-week follow-up. The study, which had a target enrollment of 110 patients, primarily assessed the drug candidate in terms of disease progression.
AMX0035 also failed to outperform placebo in terms of secondary outcomes, including improvements in motor aspects of activities of daily living. The drug candidate was generally well-tolerated, according to Amylyx, with a safety profile consistent with that in prior studies. Given these findings, the biotech will terminate the open-label extension phase of ORION and will no longer push through to its Phase III portion.
Affecting about 7 of every 100,000 people, progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder that can turn fatal if left unchecked. Patients with this disorder suffer from dysfunctional movement, gait and balance. PSP also compromises swallowing and speech. Overall, the life expectancy among PSP patients runs from about six to eight years after initial diagnosis.
While Amylyx will no longer test AMX0035 for PSP, it will still continue assessments for the drug in Wolfram syndrome, with an update expected later this year.
Amylyx’s GLP-1 therapy avexitide will remain its “highest priority” moving forward, co-CEOs Josuha Cohen and Justin Klee said in a prepared statement on Wednesday. Avexitide is currently being studied for post-bariatric hypoglycemia (PBH) and the company expects to complete enrollment into the Phase III LUCIDITY trial this year. Topline findings from that study are expected in the first half of 2026.
Amylyx acquired avexitide from Eiger BioPharmaceuticals in July 2024 for $35 million. At the time of the purchase, the asset had already been tested in five trials for PBH, with mid-stage studies demonstrating significant reductions in hypoglycemic events.
Aside from avexitide, Amylyx is also advancing the antisense oligonucleotide AMX0114 for amyotrophic lateral sclerosis (ALS). Early cohort results from the Phase I LUMINA study are expected later this year, Cohen and Klee said in the company’s statement.
Wednesday’s mid-stage stumble comes as Amylyx tries to regain its footing in the market after voluntarily withdrawing its ALS therapy Relyvrio. The drug, which was approved in September 2022, failed a Phase III trial in March 2024, unable to significantly improve functional performance of patients versus placebo.
