some study updates


UPDATE: Following a temporary pause in August this year, Novartis has made the difficult decision to permanently stop dosing with branaplam. While branaplam, an oral HTT mRNA splice modulator, acted as hoped by lowering the levels of mHTT protein in the spinal fluid in people with HD, peripheral neuropathy also occurred in many (but not all) participants receiving active doses of the drug. Novartis has further stated that neither a different nor a lower dosing regime is likely to improve the safety profile and as such, the branaplam development programme will not progress further. The decision to stop dosing was endorsed by the study’s independent Data Monitoring Committee and the VIBRANT-HD Steering Committee. While clearly disappointing, the decision to stop was made in a timely fashion and reflects the overarching commitment to the safety of participants in clinical research. (Summer 2023)

EHDN statement on the pausing of dosing in the endorsed clinical trials VIBRANT and AMT-130

The EHDN is closely monitoring recent developments in two ongoing clinical trials: the VIBRANT trial sponsored by Novartis and the AMT-130 trial sponsored by Uniqure. Both trials are endorsed by EHDN and represent distinct pharmacological approaches towards the shared goal of lowering expression of the Huntingtin protein in patients with HD. The safety concerns that have arisen appear to be unrelated to one another and are currently being analysed. While this is a sobering moment on the road towards the development of effective interventions against the devastations of HD, these setbacks are not unexpected and are also a reflection of the robust trial activity in the field. It is also a reminder of the risks that participants in such trials are taking to advance our cause as well as the importance and appropriate application of intense surveillance of participant safety. Continued follow up of already-dosed participants in these trials is critical.

The EHDN is committed to continuously improving clinical trials and thus it is our obligation to learn as much as possible from these developments. We look forward to the analyses of results by the trial sponsors along with the wider HD research community. (August 2023)