Phase 2 HELIOS Trial Shows AMX0035 Benefits in Wolfram Syndrome

Amylyx Pharmaceuticals recently reported interim findings from its Phase 2 clinical trial of AMX0035 in adult patients with Wolfram syndrome, a rare genetic disorder. The study, known as HELIOS, revealed that after 24 weeks of treatment, the drug showed potential in improving pancreatic function and blood sugar control, as indicated by C-peptide levels and other glucose metabolism markers. Typically, these conditions would worsen over time with the disease.

The eight participants in the study not only met the pre-specified criteria for improvement or stabilization of the disease but also reported some enhancement in vision. The drug was found to be well-tolerated with mild or moderate adverse events, and no serious events were related to the treatment.

Dr. Fumihiko Urano, Principal Investigator of the trial and a professor at Washington University School of Medicine in St. Louis, highlighted the significance of the findings, stating that disease stabilization is clinically meaningful for patients and doctors alike. The HELIOS trial is an open-label study involving 12 participants and aims to assess the drug's impact on the progression of diabetes, vision loss, and overall disease burden.

The primary goal of the trial is to measure changes in C-peptide levels, an indicator of pancreatic function and blood sugar control. The interim analysis showed an average increase in total C-peptide response, which is contrary to the expected decline in Wolfram syndrome patients. Additionally, most participants exhibited a shorter time to peak C-peptide response, suggesting an improved pancreatic response.

Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx, commented on the promising results, noting that the improvements in C-peptide levels differ from the typical progression of the disease. AMX0035 is believed to target endoplasmic reticulum stress and mitochondrial dysfunction, which are linked to the WFS1 gene mutations found in most Wolfram syndrome patients.

The interim data also showed improvements in hemoglobin A1C levels and time in target glucose range for most participants. Furthermore, visual acuity, which usually deteriorates in Wolfram syndrome, showed some improvement in the study participants.

Justin Klee and Joshua Cohen, Co-CEOs of Amylyx, expressed gratitude to the Wolfram syndrome community for their support and collaboration. They also mentioned plans to engage with regulatory authorities regarding the development path for Wolfram syndrome and anticipate presenting the topline data for all participants later in the year.

The HELIOS trial is part of ongoing research into the potential of AMX0035, a combination of sodium phenylbutyrate and taurursodiol, in treating neurodegenerative diseases by addressing ER stress and mitochondrial dysfunction. Wolfram syndrome, characterized by early-onset diabetes, optic nerve atrophy, and neurodegeneration, has no cure and leads to a poor prognosis for affected individuals.