Amylyx’s Withdrawn ALS Drug Shows Promise in Wolfram Syndrome

Rare Daily Staff

Amylyx Pharmaceuticals reported positive interim data from the ongoing phase 2 HELIOS clinical trial of its experimental therapy AMX0035 in adults living with Wolfram syndrome, a rare, progressive genetic disease.

The interim data from eight participants who have completed 24 weeks of treatment demonstrated that AMX0035 had a clinically meaningful effect on key outcomes measuring the progression of diabetes, visual decline, and overall disease burden in adult participants living with Wolfram syndrome.

Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of WS include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. Genetic and experimental evidence suggest that endoplasmic reticulum dysfunction is a critical pathogenic component of WS. The prognosis of WS is poor, and many people with the disease die prematurely with severe neurological disabilities.

AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol. It had been approved as Relyvrio to treat amyotrophic lateral sclerosis (ALS) in adults in the U.S., but the company withdrew it from the market after disappointing phase 3 results failed to demonstrate its efficacy. AMX0035 is being studied for the potential treatment of other neurodegenerative diseases, and Amylyx is exploring its treatment in other populations and regions.

“This community has an urgent unmet need for disease modifying treatments. Outcomes for people with Wolfram syndrome consistently worsen over time, so disease stabilization alone is clinically meaningful for both patients and their doctors,” said  Fumihiko Urano, principal investigator of the phase 2 HELIOS clinical trial in Wolfram syndrome and professor of medicine in the Division of Endocrinology, Metabolism and Lipid Research at Washington University School of Medicine in St. Louis. “The interim results from HELIOS that demonstrate improvement across multiple organ systems impacted by this progressive disease are encouraging.”

The safety profile of AMX0035 in HELIOS was consistent with prior safety data. AMX0035 was generally well-tolerated. The majority of adverse events (AEs) were mild or moderate, and there were no serious AEs related to AMX0035 treatment. The most common AE was diarrhea.

In September 2022, researchers from Washington University School of Medicine in St. Louis, including Dr. Urano, in collaboration with Amylyx, published positive preclinical data on AMX0035 in beta cell, neuronal cell and mouse models of Wolfram syndrome in the peer-reviewed Journal of Clinical Investigation Insight. Amylyx announced that the FDA granted orphan drug designation to AMX0035 for the treatment of Wolfram syndrome in November 2020.

Photo: Fumihiko Urano, principal investigator of the phase 2 HELIOS clinical trial in Wolfram syndrome and professor of medicine in the Division of Endocrinology, Metabolism and Lipid Research at Washington University School of Medicine in St. Louis