Amylyx Pharmaceuticals announced positive topline results from the Phase 2 HELIOS clinical trial, revealing that AMX0035 (sodium phenylbutyrate and taurursodiol) demonstrated sustained improvements in adults living with Wolfram syndrome. The open-label trial, involving 12 adults, showed improvements in pancreatic function, glycemic control, and visual acuity after 24 weeks of treatment. These findings suggest that AMX0035 could potentially alter the course of this rare, progressive disease, which currently lacks approved treatment options.
HELIOS Trial Results
The HELIOS trial (NCT05676034) was a single-site, single-arm, open-label Phase 2 study designed to assess the safety, tolerability, and efficacy of AMX0035 in adults with Wolfram syndrome. The primary efficacy endpoint was the change from baseline in C-peptide response, a measure of pancreatic beta cell function, assessed using a mixed meal tolerance test (MMTT) at Week 24. Secondary endpoints included assessments of glycemic control, visual acuity, and overall disease status.
The trial demonstrated a statistically significant improvement in C-peptide response from baseline to Week 24, with a change of +3.8 minng/mL (SE: 19.3) in the Intent to Treat group (N=12) and +20.2 minng/mL (SE: 11.2) in the Per Protocol group (N=11). Furthermore, participants showed improved glycemic control, as indicated by changes in hemoglobin A1c (HbA1c) and time in target glucose range. Visual acuity also improved in some participants, and both clinician-reported and patient-reported global impressions of change indicated disease stabilization or improvement in all participants.
Longer-term data from participants who completed Week 36 (n=10) and Week 48 (n=6) assessments showed sustained improvements in C-peptide and HbA1c levels, reinforcing the potential of AMX0035 to provide lasting benefits.
Safety and Tolerability
AMX0035 was generally well-tolerated in the HELIOS trial, with all adverse events (AEs) being mild or moderate. There were no serious AEs related to AMX0035 treatment. The most common AE reported was diarrhea, consistent with previous safety data.
Expert Commentary
"The topline results of HELIOS indicate that AMX0035 has the potential to favorably change the trajectory of Wolfram syndrome… and show an improvement on multiple measures of pancreatic beta cell function, glycemic control, and vision," said Fumihiko Urano, MD, PhD, Principal Investigator of the Phase 2 HELIOS clinical trial. He added, "These data are encouraging since Wolfram syndrome is a progressive disease."
About Wolfram Syndrome and AMX0035
Wolfram syndrome is a rare, monogenic neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. It affects approximately 3,000 people in the U.S. Common manifestations include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. The prognosis is generally poor, with many individuals dying prematurely due to severe neurological disabilities.
AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO), designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction. It is also being studied as a potential treatment for progressive supranuclear palsy.
Regulatory Status and Future Plans
The FDA and the European Commission have granted Orphan Drug Designation to AMX0035 for the treatment of Wolfram syndrome. Amylyx Pharmaceuticals plans to engage with the FDA to discuss a Phase 3 program for AMX0035 in Wolfram syndrome.
