Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) has announced that the European Commission has granted Orphan Drug Designation to AMX0035, its proprietary fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO), for treating Wolfram syndrome. This designation follows a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA).
Wolfram syndrome is a rare, progressive genetic disorder characterized by early-onset diabetes, optic nerve atrophy, deafness, diabetes insipidus, and neurodegeneration. There are currently no approved treatments for this condition, and it often leads to severe neurological disabilities and premature death.
The FDA previously granted AMX0035 Orphan Drug Designation in 2020 for Wolfram syndrome. The EMA’s Orphan Drug Designation is awarded to products intended for rare, life-threatening, or chronically debilitating conditions where they may offer significant benefits over existing treatments.
Amylyx recently shared positive interim data from its Phase 2 HELIOS study, which included eight Wolfram syndrome patients assessed at Week 24. The results showed that AMX0035 improved pancreatic function and glycemic control, as indicated by markers such as C-peptide and HbA1c. All participants met predefined responder criteria, showing improvement or stabilization in their condition according to Patient Reported Global Impression of Change (PGIC) and Clinical Reported Global Impression of Change (CGIC) scales. Most participants reported some improvement in vision, which is significant given that disease progression is typically expected. AMX0035 was well tolerated, and topline data from all 12 participants will be reported later this fall.
Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx, stated, “Wolfram syndrome is a classic example of an endoplasmic reticulum (ER) stress disorder linked to WFS1 mutations. AMX0035 aims to address ER stress and mitochondrial dysfunction. The HELIOS interim data showing stabilization or improvement at Week 24 is promising. We are eager to share the final data this fall and to potentially meet an urgent medical need with no current treatment options.”
About Wolfram Syndrome
Wolfram syndrome is a rare, progressive genetic disorder that presents with childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Patients commonly experience diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, and neurogenic bladder. The disease has a poor prognosis, with many individuals facing premature death and severe neurological impairments. Approximately 3,000 people in the United States are affected by Wolfram syndrome.
The syndrome is characterized by endoplasmic reticulum (ER) stress and mitochondrial dysfunction, driven by mutations in the WFS1 gene. This gene encodes wolframin, a protein involved in ER function and calcium regulation. Loss of wolframin function leads to ER stress and disrupted mitochondrial dynamics.
