Amylyx Halts AMX0035 Development for Rare Neurodegenerative Disorder

Amylyx Pharmaceuticals has discontinued the clinical development program for AMX0035, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol, for the treatment of progressive supranuclear palsy (PSP).

The decision was made based on data from the phase 2b/3 ORION trial (ClinicalTrials.gov Identifier: NCT06122662), which evaluated AMX0035 in adults with PSP who were experiencing symptoms for less than 5 years. To be eligible for the trial, patients had to have a score of less than 40 on the total (28-item) PSP rating scale (PSPRS). Total scores on PSPRS range from 0 to 96, with higher scores indicating more progressed disease.

Findings showed treatment with AMX0035 was not associated with a statistically significant improvement in PSPRS score (primary endpoint) compared with placebo at 24 weeks. The trial also missed its secondary endpoints; no statistically significant change was observed with AMX0035 in the 10-item PSPRS score or on the Movement Disorder Society-Unified Parkinson Disease rating scale, which measures motor aspects of activities of daily living.

“We set a high bar for AMX0035 in PSP and made a commitment to base our decision-making on the totality of the data and the potential for clinically meaningful outcomes for those living with PSP,” said Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx. “While we are disappointed in these results, we believe these data will inform the PSP trial literature as well as deepen scientific understanding of this devastating disease.”

AMX0035 is currently being investigated in a phase 2 trial (ClinicalTrials.gov Identifier: NCT05676034) for Wolfram syndrome, a progressive neurodegenerative disease that is characterized by childhood-onset diabetes and optic nerve atrophy. The combination therapy is expected to work synergistically to slow neurodegeneration, targeting both endoplasmic reticulum stress and mitochondrial dysfunction.

This article originally appeared on MPR