8th International Wolfram Symposium Presentation Mathias Leinders – Amylyx Pharmaceuticals
8th International Wolfram Symposium Presentation Mathias Leinders – Amylyx Pharmaceuticals
Helios – A Phase II Study of Safety and Efficacy of AMX0035 in Wolfram Syndrome
Summary: Update on the clinical trial design of Helios, and the rationale for using AMX0035 as potential treatment for Wolfram Syndrome.
Points noted:
- AMX0035 is a combination therapy of two compounds– TUDCA (tauroursodeoxycholic acid) and sodium phenylbutyrate (PB).
- Approved in the US for ALS, not currently approved in the EU.
- Investigational drug for WS. Received orphan drug status in US.
- Shown to decrease neuronal death, mitigate ER stress and mitochondrial dysfunction.
- Excellent safety and tolerability profile shown in previous studies (Ph III in ALS). Taste issues have been reported previously (AMX0035 = sachet).
- Currently conducting a collaboration with Dr Urano (preclinical and clinical).
- As part of this collaboration, an open label Ph II study has started in US to recruit 12 patients to assess safety (using standard endpoints), tolerability, various measurements (e.g. beta cell function), and exploratory biomarkers.
- Study will monitor C-peptide levels (as a surrogate endpoint) over 24-week period. Patients will therefore need to be relatively healthy to be able to participate (It was noted that not many patients will meet the inclusion criteria required for C-peptide levels). Based on learnings from the dantrolene trial, the target of 12 patients should be achieved.
- The study aims to assess whether there is value in treating WS patients as early as possible and if data are encouraging will expand to larger and longer studies.
- The study protocol includes a 4-hour mixed meal tolerance test (MMTT) (which it was noted is a big ask for patients and researchers). This test was specifically requested by the FDA. If data are encouraging, the aim is to propose to reduce MMTT in a future larger trial.
- If data are encouraging, this will help to spur development in a juvenile programme.
- First patient recruited to this study April 2023 (week prior to the Symposium).