Amylyx HELIOS Trial Week 48 Results and Updates – Virtual Global Research and Trial Updates

Overview

Jamie Timmons from Amylyx presented the HELIOS trial results for Week 48, focusing on the investigational therapy AMX 35 (sodium phenylbutyrate and ursodil) for Wolfram syndrome. The trial, involving 12 participants, showed improvements in pancreatic beta cell function, insulin secretion, and glycemic control, with a significant reduction in hemoglobin A1c levels. The therapy was generally well-tolerated, with diarrhea being the most common side effect. The phase three trial is planned for the second half of next year, with a larger participant pool and potential inclusion of younger patients and those with single-allele mutations. Use is not currently available due to drug supply limitations.

Action Items

• Provide the specific mutations included in the HELIOS trial.
• Share updates on the potential for including younger patients and patients with a single recessive mutation in the phase 3 trial.
• Provide an update on the status of a compassionate use program for PB and turso.

Outline

Introduction

• Jamie Timmons mentions the investigational therapy, AMX 35, and its combination of sodium phenylbutyrate and ursodil.
• The therapy targets endoplasmic reticulum stress and mitochondrial dysfunction pathways relevant to Wolfram syndrome.

Overview of the HELIOS Trial

• Jamie explains the HELIOS study, an open-label phase two trial with 12 participants.
• The study aims to evaluate the impact of PB and turso on relevant outcome measures in Wolfram syndrome.
• The trial is extended to continue following participants, with data from week 24 and week 48 being shared.
• Key inclusion criteria include participants aged 17 or older with documented recessive mutations in the WFS1 gene and stimulated C-peptide levels of at least 0.2.

Participant Baseline Characteristics

• Jamie shares the baseline characteristics of the participants, including median age (25 years), gender (majority female), and median time since diagnosis (5 years).
• Participants have various symptoms, such as diabetes mellitus, diabetes insipidus, hearing loss, and vision loss.
• The study includes two populations: intent-to-treat (ITT) and per-protocol (PP), with one participant excluded due to having only one pathogenic allele.

C-Peptide Response Data

• Jamie discusses the C-peptide response data, showing improvements in pancreatic beta cell responsiveness at weeks 24 and 48.
• The data indicates earlier and higher peaks in C-peptide response, indicating better pancreatic cell function.
• Different ways to analyze the data, such as area under the curve and time to peak, show consistent improvements.
• The study also shows improvements in hemoglobin A1c, indicating better blood sugar control over time.

Additional Endpoints and Participant Feedback

• Jamie reviews other endpoints, including insulin dose stability, time in target glucose range, and best corrected visual acuity.
• Qualitative interviews with participants reveal positive changes in various Wolfram syndrome-related symptoms.
• The study shows that PB and turso are generally well-tolerated, with diarrhea being the most common adverse event.
• Jamie emphasizes the limitations of the study, including its open-label design and small sample size.

Phase Three Trial Planning

• Jamie provides an update on the phase three trial, expected to start in the second half of next year.
• The study design is still under discussion with the FDA, and more participants will be needed.
• The phase three trial will likely include a placebo control group.
• Jamie encourages participants to stay informed and involved in the trial design process.

Questions and Answers

• Wolfram Syndrome UK asks about the drop in participants from week 24 to week 48, and Jamie explains that some participants left for personal reasons.
• A participant from Ankara, Turkey, inquires about the possibility of participating in the next phase of the study, and Jamie explains the steps involved in setting up the trial.
• Jamie confirms that the study will consider younger patients and those with recessive mutations on one allele, pending FDA approval.
• Stephanie Gebel asks about compassionate use, and Jamie explains that it is not currently available due to drug supply limitations but will be considered once the phase three trial is up and running.