Prevalence of Wolfram syndrome and Amylyx program status
There are currently no approved therapies for the approximately 3,000 people in the U.S., and more around the world, living with Wolfram syndrome. The FDA and the European Commission granted Orphan Drug Designation to AMX0035 for the treatment of Wolfram syndrome in November 2020 and August 2024, respectively.
We initiated HELIOS (NCT05676034), a 12-participant, single-site, single-arm, open-label, Phase 2 clinical trial designed to evaluate the safety and tolerability of AMX0035 and various measures of endocrinologic, neurologic, and ophthalmologic function in adult participants living with Wolfram syndrome.
In May 2025, we announced positive Week 48 data from the Phase 2 open-label HELIOS clinical trial of AMX0035 in adults living with Wolfram syndrome. Consistent with the HELIOS trial’s previously presented primary efficacy outcome of improvement in pancreatic function, as measured by C-peptide response to a mixed-meal tolerance test at Week 24, treatment with AMX0035 through Week 48 demonstrated continued and sustained improvement in pancreatic beta cell function.
Treatment with AMX0035 from Week 24 to Week 48 also showed sustained improvements or stabilization in glycemic control, as measured by hemoglobin A1c (HbA1c) and time in target glucose range assessed by continuous glucose monitoring, as well as visual acuity. All participants with available measurements met the responder criteria, defined as either improvement or no change, on both the Patient Global Impression of Change (PGI-C) and Clinician Global Impression of Change (CGI-C) at Weeks 24 and 48, indicating stability or improvement in their Wolfram syndrome-related symptoms. Results from qualitative on-study interviews further supported the potential positive impact of AMX0035 on symptom burden.
The safety profile of AMX0035 in HELIOS Week 48 data were consistent with prior safety data from the studies of AMX0035. All adverse events (AEs) were mild or moderate, and there were no serious AEs related to AMX0035 treatment.
Data from participants at Week 48 and ongoing discussions with the FDA will inform the design of a Phase 3 trial of AMX0035 in Wolfram syndrome.