Amylyx Gets EU Orphan Drug Status for AMX0035 to Treat Wolfram Syndrome

Amylyx Pharmaceuticals, Inc., a company known for its focus on developing treatments for serious and life-threatening diseases, has announced that the European Commission (EC) has granted Orphan Drug Designation to AMX0035 for the treatment of Wolfram syndrome. This designation follows a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA). AMX0035 is a fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO), also known outside the U.S. as ursodoxicoltaurine.

Wolfram syndrome is a rare, progressive, and monogenic disease characterized by childhood-onset diabetes mellitus, optic nerve atrophy, deafness, diabetes insipidus, and neurodegeneration. Typically, individuals with this disease face a grim prognosis, often dying prematurely with severe neurological disabilities. Currently, there are no approved treatments for this condition.

The FDA had previously granted AMX0035 Orphan Drug Designation for the treatment of Wolfram syndrome in 2020. The EMA awards this designation to products aimed at treating, preventing, or diagnosing rare and life-threatening conditions that have the potential to provide significant benefits over existing treatments.

In recent developments, Amylyx presented encouraging data from an interim analysis of its Phase 2 HELIOS study. This study included eight participants with Wolfram syndrome, assessed at Week 24. Results indicated that AMX0035 improved pancreatic function and glycemic control, evaluated using C-peptide, HbA1c, and other glucose metabolism markers. All eight participants met predefined responder criteria, showing either improvement or stabilization of the disease based on both the Patient Reported Global Impression of Change (PGIC) and the Clinical Reported Global Impression of Change (CGIC) scales. Notably, most participants also reported some improvement in vision. Given that a progressive decline is expected in Wolfram syndrome, even stabilization of the disease is clinically meaningful. AMX0035 was generally well-tolerated among participants, and Amylyx plans to report topline data from all 12 participants at Week 24 in the coming fall.

Dr. Camille L. Bedrosian, Chief Medical Officer at Amylyx, emphasized the significance of Wolfram syndrome having well-defined measurable biomarkers, robust supporting preclinical data, and a clear rationale for AMX0035 based on its mechanism of action. Wolfram syndrome is considered a prototypical endoplasmic reticulum (ER) stress disorder due to the connection between WFS1 mutations and ER stress. AMX0035 is believed to target both ER stress and mitochondrial dysfunction, which are central pathways in the disease's progression. The interim data from the HELIOS study showed stabilization or improvement across key outcomes at Week 24, following strong preclinical research that demonstrated clear effects in cellular and animal models. Amylyx aims to meet the urgent unmet medical need for Wolfram syndrome, given the lack of approved treatment options.

Wolfram syndrome is known for its rare and progressive nature, manifesting in childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common symptoms include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurological challenges. Literature reports that approximately 3,000 individuals in the United States are affected by this condition. The disease is driven by ER stress and mitochondrial dysfunction, primarily due to mutations in the WFS1 gene, which encodes the protein wolframin. This protein is crucial for proper ER function and calcium regulation. Loss of wolframin function leads to ER stress and impaired mitochondrial dynamics.

AMX0035 is an oral, fixed-dose combination of PB and TURSO, designed to mitigate neurodegeneration by targeting ER stress and mitochondrial dysfunction simultaneously. Preclinical studies have shown that this combination is more effective in preventing cell death and neurodegeneration than targeting either pathway alone. AMX0035 is being investigated for its potential to treat various neurodegenerative diseases, including Wolfram syndrome and progressive supranuclear palsy (PSP).

The HELIOS trial, a Phase 2 open-label study, is designed to assess the safety and tolerability of AMX0035, along with its effects on endocrinological, neurological, and ophthalmologic functions in adult participants with Wolfram syndrome.

Amylyx Pharmaceuticals is dedicated to discovering and developing new treatment options for communities with high unmet needs, focusing on serious and fatal diseases. The company has ongoing preclinical and clinical development programs in neurodegenerative, neuroendocrine, and endocrine diseases, with a commitment to keeping affected communities at the forefront of its decisions. Amylyx is headquartered in Cambridge, Massachusetts.

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