The decision was based on the results of a pre-planned review of the data from the Phase III study conducted by an unblinded Independent Data Monitoring Committee (iDMC). The iDMC made its recommendation based on the investigational therapy’s potential benefit/risk profile for study participants. No new or emerging safety signals were identified for tominersen in the review of the data from this study. Roche intends to continue following participants for safety and clinical outcomes, without the dosing of the investigational medicine or placebo. Once full data from the Phase III study are available and analysed, Roche will share learnings and future plans with the HD community.
This is very unfortunate news to deliver on the tominersen Phase III study and we know it will be especially difficult for people with Huntington’s disease to hearLevi Garraway
Dosing will be paused in the open-label extension study (GEN-EXTEND) of tominersen while data are carefully analysed to inform next steps on this study. “This is very unfortunate news to deliver on the tominersen Phase III study and we know it will be especially difficult for people with Huntington’s disease to hear. The HD community currently has no treatments to stop or slow the progression of this rare neurodegenerative disease that impacts families across generations.” said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development. “GENERATION HD1 is the largest clinical trial in Huntington’s disease to date and we do know that the data generated will significantly advance our understanding of huntingtin-lowering as a potential treatment approach. We would like to thank all of the individuals and families participating in the study for their contribution, as well as the broader HD community for their commitment and collaboration.”
The Phase I PK/PD study (GEN-PEAK) of tominersen and the observational Roche HD Natural History Study will continue.
About tominersen and the clinical trials
Tominersen, previously IONIS-HTTRx or RG6042, is an investigational antisense therapy designed to reduce the production of all forms of the huntingtin protein (HTT), including its mutated variant, mHTT. In December 2017, Roche licensed the investigational molecule from Ionis Pharmaceuticals.
Tominersen is being investigated in HD in the following clinical studies:
- GENERATION HD1: a randomised, multicenter, double-blind, placebo-controlled Phase III clinical study evaluating the efficacy and safety of treatment with tominersen in people with manifest HD over 25 months. Study participants were randomised to either 120 mg every-2-months or 120 mg every-4-months intrathecal injections of tominersen, or placebo. The study has recruited 791 participants from 18 countries around the world.
- GEN-EXTEND: an open label extension study for participants coming from any Roche HD study. Participants receive 120mg tominersen every-2-months or every-4-months in the study.
- GEN-PEAK: a Phase I study aiming to better understand the pharmacokinetics of tominersen and how tominersen affects mHTT levels and other markers in the spinal fluid and blood, which studies a range of doses from 30 mg to 120 mg of tominersen over two administrations.