Amylyx Pharmaceuticals, Inc. announced interim data from the ongoing Phase 2 HELIOS clinical trial of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]) in adults living with Wolfram syndrome, a rare, progressive genetic disease impacting approximately 3,000 people in the U.S. The interim data from eight participants who have completed 24 weeks of treatment demonstrated that AMX0035 had a clinically meaningful effect on key outcomes measuring the progression of diabetes, visual HELIOS is an ongoing, open-label Phase 2 study in 12 participants designed to evaluate if AMX0035 slows progression of diabetic, visual, and other measures in people living with Wolfram syndrome and to evaluate safety and tolerability. The primary efficacy endpoint of the trial measures change from baseline in C-peptide, an established, objective laboratory measure of pancreatic beta cell function and glycemic control, assessed using a Mixed Meal Tolerance Test (MMTT). Secondary and exploratory outcomes include the measurement of other diabetic responses and other domains affected by the disease.

The interim analysis performed is based on a data cutoff as of March 5, 2024, which includes all participants who completed their Week 24 assessments as of the cutoff (n=8). In this interim analysis of eight participants treated with AMX0035, increases were observed on average in the primary outcome of total C-peptide response (C-peptide AUC change from baseline) including in the 90-minute response at Week 24 (+15.6 ng min/mL, 95% CI: [1.3, 30.0]). In Wolfram syndrome, progressive decline would have been expected on this measure.

Additionally, seven out of eight participants demonstrated at least a 30-minute shorter time to peak C-peptide response. In Wolfram syndrome, a progressive increase in time to peak C-peptide response, indicating slower pancreatic response, and reduced total C-peptide response would The following includes additional key data from the interim analysis: Hemoglobin A1C (HbA1c) is a measure of glycosylated hemoglobin which serves as a metric of how well sugar levels are being controlled in the blood. HbA1c was reduced by 0.26% (SE: 0.15%) on average after 24-weeks of AMX0035 treatment with six out of eight participants showing improvement in their HbA1c.

Many studies have associated reduced HbA1c with better clinical outcomes. All participants had continuous glucose monitoring in the study allowing for a rigorous measurement of the time in target glucose range. The absolute time in target glucose range improved on average by +7.1% (SE: 4.7%).

Five out of eight participants had improvements in the time in target glucose range. Increased time in target glucose range is associated with better diabetic outcomes. Visual acuity was measured by the Snellen chart.

Wolfram syndrome results in progressive optic nerve atrophy leading to relentless loss of both visual acuity and color vision, and eventually blindness. On average in HELIOS, visual acuity improved +0.05 -LogMAR (SE: 0.09) with five out of eight participants demonstrating some improvement in vision. Of those who improved, one participant changed from legally blind to legally sighted.

Optical coherence tomography outcomes have not yet been assessed and will be included in final data analysis from HELIOS. All participants (8 out of 8) showed disease stability or improvement at Week 24, as measured by The Clinician Report Global Impression of Change (CGIC) and Patient Reported Global Impression of Change (PGIC). Improvement was noted by the CGIC in 62.5% of cases (5 out of 8) and by the PGIC for 75% of cases (6 out of 8) with the remainder reporting disease stability on both the CGIC and PGIC.

These outcome measures are designed to report if the overall burden of disease has improved, stayed the same, or worsened from the clinician?s or patient?s perspective. The safety profile of AMX0035 in HELIOS was consistent with prior safety data. AMX0035 was generally well-tolerated.

The majority of adverse events (AEs) were mild or moderate, and there were no serious AEs related to AMX0035 treatment. The most common AE was diarrhea.