Amylyx Reports Positive Phase 2 HELIOS Trial Results for AMX0035 in Wolfram Syndrome

Amylyx Pharmaceuticals, Inc., has announced promising topline results from the Phase 2 HELIOS clinical trial for their drug AMX0035, aimed at treating Wolfram syndrome. Wolfram syndrome is a rare, genetic neurodegenerative disorder that affects around 3,000 individuals in the United States. The Phase 2 HELIOS trial involved 12 adult participants and assessed the safety and efficacy of AMX0035, a combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO).

The primary efficacy endpoint for the study was the change in pancreatic function, measured through C-peptide response after 24 weeks of AMX0035 treatment. The results were positive, showing an improvement in pancreatic function, a significant finding given that a decline in this function is typically expected in the natural progression of Wolfram syndrome. Additionally, the trial observed stabilization or improvement across various secondary endpoints, including measures of glycemic control such as hemoglobin A1c (HbA1c) levels, time in target glucose range, and visual acuity.

Longer-term data for participants who completed assessments at Week 36 and Week 48 further demonstrated sustained improvements over time. All participants who reached these longer-term milestones showed continuous improvement or stability in their disease condition. Notably, the study's findings were presented at the ISPAD 50th Annual Congress and during a webcast held by Amylyx.

Dr. Fumihiko Urano, the Principal Investigator of the HELIOS trial and a professor at Washington University School of Medicine in St. Louis, remarked on the potential of AMX0035 to alter the course of Wolfram syndrome. He highlighted the sustained improvement in pancreatic beta cell function and glycemic control as particularly encouraging, given the progressive nature of the disease.

The analysis included data from all 12 participants at Week 24 and data from those who completed Week 36 (n=10) and Week 48 (n=6) assessments. The primary endpoint assessed the change in C-peptide response using a mixed meal tolerance test at Week 24. Results showed a mean change in C-peptide response from baseline at 120 minutes, indicating an improvement in pancreatic function. Secondary endpoints examined other diabetic measures and additional domains affected by the disease.

AMX0035 was generally well-tolerated, with all adverse events reported as mild or moderate and no serious adverse events related to the treatment. The most common adverse event was diarrhea.

Dr. Camille L. Bedrosian, Chief Medical Officer of Amylyx, emphasized that the outcomes suggest AMX0035 could lead to meaningful improvements in disease progression. The drug targets endoplasmic reticulum stress and mitochondrial dysfunction, pathways implicated in Wolfram syndrome due to mutations in the WSF1 gene.

The FDA and the European Commission have granted Orphan Drug Designation to AMX0035 for Wolfram syndrome, recognizing its potential to address this high unmet medical need. The HELIOS trial continues to build a case for the efficacy and safety of AMX0035, with Amylyx planning to engage with the FDA and other stakeholders to advance to a Phase 3 program. An update on the progress and further plans is expected in 2025.

The HELIOS trial, which began in September 2022, is designed to assess the effect of AMX0035 on various measures of endocrinological, neurological, and ophthalmologic function in adults with Wolfram syndrome. The study involves up to 96 weeks of treatment followed by a four-week safety follow-up.

Wolfram syndrome is characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration, among other symptoms. The prognosis is generally poor, with many affected individuals dying prematurely due to severe neurological disabilities. AMX0035 aims to slow or mitigate neurodegeneration by addressing the underlying cellular stress pathways.

Amylyx remains committed to discovering and developing new treatments for diseases with high unmet needs, focusing on serious and fatal neurodegenerative and endocrine conditions. The company's headquarters is located in Cambridge, Massachusetts.