Mechanistic Approach Behind AMX0035 in Progressive Supranuclear Palsy: Gunter Hoglinger, MD

WATCH TIME: 4 minutes

"It [AMX0035] has a strong component that plays on mitochondrial dysfunction, which is the total residual component, and then the sodium phenylbutyrate component which plays and stabilizes the unfolded protein response."

Earlier this year, Amylyx Pharmaceuticals announced a new trial, ORION, to assess the safety and efficacy of AMX0035 (Relyvrio), a previously approved therapy for amyotrophic lateral sclerosis (ALS), in patients with progressive supranuclear palsy (PSP), another neuromuscular disease. The trial aims to enroll 600 adult participants with PSP for a 52-week double-blind treatment period, followed by an open-label extension lasting the same time length. Change in disease progression through the 28-item, validated Progressive Supranuclear Palsy Rating Scale (PSPRS) will be the primary end point.

Led by Gunter Hoglinger, MD, the study will also assess AMX0035’s impact on motor aspects of activities of daily living, as well as brain atrophy, survival, burden, and quality of life. The trial, expected to initiate by the end of 2023, will also include biomarker assessments of neuronal injury and neuroinflammation. AMX0035, the third approved medication to show slowing of ALS disease progression, has been proposed to mitigate tau pathology in PSP through multiple pathways, with preclinical evidence to support this.

In an interview with NeurologyLive®, Hoglinger, professor of neurology and translational neuroscientist at Ludwig-Maximillian’s University Munich, provided insight on the pathophysiological changes in PSP and why AMX0035 holds potential to treat patients with the disease. In addition, he discussed the mechanism of action of the drug, what preclinical data has demonstrated, and the differences and similarities between PSP and ALS.