Roche has discontinued two Huntington’s disease studies for investigational antisense therapies being developed in collaboration with Ionis Pharmaceuticals, according to a July 10 letter to the Huntington’s disease community. The company will not continue with the Phase 2 GENERATION HD2 study after tominersen failed to meet its key efficacy objective. In addition, a separate clinical trial evaluating RG6496 was stopped based on new data from a parallel animal study.
Roche said these developments are “deeply disappointing,” but stated that the failures of the two trials “have coincided by chance.” A Roche spokesperson said, “based on the totality of data,” both programs would end. The spokesperson also said that Roche and Ionis continue to collaborate on other programs.
For Ionis Pharmaceuticals, this news added to existing challenges. On Thursday morning, Ionis announced that its AstraZeneca-partnered Wainua failed the Phase 3 CARDIO-TTRansform trial in transthyretin amyloidosis cardiomyopathy. Following this announcement, Ionis’ shares dropped nearly 24% on Thursday but recovered slightly in premarket trading Friday.
Tominersen and RG6496 are antisense therapies designed to target huntingtin protein mutations associated with cognitive decline and motor problems in Huntington’s disease. RG6496 is more targeted and binds specifically to a variation in huntingtin RNA, while tominersen lowers expression of all types of huntingtin protein—including healthy ones. Tominersen previously faced setbacks: Roche suspended an early-stage study in 2020 due to catheter-related infections (ultimately deemed unrelated) and discontinued the Phase 3 GENERATION HD1 trial in March 2021 after a review found disappointing results.
Despite these difficulties, tominersen had been considered one of several promising therapies for Huntington’s disease alongside uniQure's gene therapy AMT-130. In September 2025, AMT-130 slowed disease progression by 75% in a Phase 1/2 study. However, regulatory uncertainty followed when the Food and Drug Administration initially decided that data from this trial were insufficient for marketing approval, before later agreeing that three-year findings could support accelerated approval.
