Roche’s decision to discontinue the Ionis-partnered trials came soon after the biotech sustained a late-stage failure in ATTR-CM.
Roche has discontinued two Huntington’s disease studies for investigational antisense therapies being developed in collaboration with Ionis Pharmaceuticals.
The pharma will no longer push through with the Phase 2 GENERATION HD2 study after the embattled asset tominersen failed to meet its key efficacy objective, Roche said in a Thursday letter to the Huntington’s disease community. Meanwhile, a separate clinical trial evaluating a candidate called RG6496 was stopped based on new data from a parallel animal study.
Roche recognized that these developments are “deeply disappointing,” but said the failure of the two trials are data-driven events that “have coincided by chance.”
Roche has made the decision to end both programs “based on the totality of data,” a company spokesperson told BioSpace in an emailed statement. Roche and Ionis continue to collaborate on other programs, the spokesperson added.
For Ionis, the news added to the difficulties of the day. Thursday morning, the company announced that its AstraZeneca-partnered Wainua failed the Phase 3 CARDIO-TTRansform trial in transthyretin amyloidosis cardiomyopathy. Ionis’ shares plunged by nearly 24% on Thursday but recovered slightly in premarket trading on Friday.
Tominersen and RG6496 are antisense therapies that work by targeting the huntingtin protein, which is mutated in Huntington’s disease and leads to the hallmark symptoms of cognitive decline and motor problems. RG6496 is designed to be more targeted and binds to a specific variation in the huntingtin RNA, ensuring that the drug only targets the mutated version of the protein.
Tominersen, meanwhile, lowers the expression of all types of huntingtin protein, even the healthy ones. The candidate has had a rough road. In 2020, Roche suspended an early-stage study of tominersen after detecting two catheter-related infections, which were ultimately deemed not drug-related. A year later, in March 2021, the pharma discontinued the Phase 3 GENERATION HD1 trial after a pre-planned review of the drug’s benefit/risk profile yielded disappointing results.
Despite its difficulties, tominersen emerged as one of the promising Huntington’s disease therapies chasing after uniQure and its gene therapy AMT-130, which in September 2025 slowed disease progression by an impressive 75% in a Phase 1/2 study.
Things became complicated for uniQure late last year, however. In November the FDA said it no longer believed data from the Phase 1/2 trial was enough to support a marketing application—despite the agency having previously agreed to the plan. Following the departure of former Commissioner Marty Makary and former Center for Biologics Evaluation and Research (CBER) director Vinay Prasad, the FDA did another 180, agreeing that three-year Phase 1/2 findings can support an accelerated approval for AMT-130. UniQure expects to file its application in the third quarter.
