Roche has decided to discontinue dosing in the Phase III GENERATION HD1 study of investigational antisense therapy, tominersen, in manifest Huntington’s disease (HD).
Licensed from Ionis Pharmaceuticals, tominersen is designed to lower all forms of huntingtin protein (HTT) production, including its mutated variant, mHTT.
The randomised, multi-centre, double-blind, placebo-controlled study is analysing the efficacy and safety of the tominersen treatment in individuals with manifest HD over 25 months.
It has so far recruited 791 subjects from 18 countries worldwide.
The latest move is 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’s recommendation to discontinue dosing is based on tominersen’s potential benefit/risk profile for study subjects.
Roche noted that no new or emergent safety signals of tominersen were detected in the review of this study data.
The company plans to continue following subjects for safety and clinical outcomes, without dosing with the investigational medicine or placebo.
Roche Global Product Development chief medical officer and head Levi Garraway said: “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.
“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.”
In an open-label GEN-EXTEND extension study, dosing with tominersen will be paused while data are evaluated to inform further steps on the study.
Furthermore, the company will continue the Phase I PK/PD GEN-PEAK study of tominersen and the observational Roche HD Natural History Study.
Roche’s cancer immunotherapy Tecentriq (atezolizumab) has demonstrated positive data in early-stage non-small cell lung cancer (NSCLC) in a pivotal Phase III study.