Roche has stopped development of two of its Huntington’s disease candidates after one failed to show benefit in a Phase II trial and another showed concerns around chronic administration.
As a result, the Swiss pharma is discontinuing the clinical programmes for both tominersen and RG6496.
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In the Phase II GENERATION HD2 trial, Roche said that when observing top-line results, the clinical study did not show meaningful efficacy when compared to placebo. This was despite the company caveating that there was a lowering of important biological markers of Huntington’s.
Meanwhile, RG6496 was being investigated in the Phase I POINT-HD trial. Roche pointed to a review of recently emerging non-clinical data that indicated long-term, chronic administration of RG6496 would not be supported.
A spokesperson for Roche said: “Based on the totality of data, Roche has made the decision to discontinue the development programmes of both tominersen and RG6496. It is important to emphasise that the decision to discontinue these programmes is based on independent, data-driven events and not related to new safety concerns for participants in these studies.”
Trials of tominersen were first initiated in 2015, while RG6496 first entered trials just months ago, with the POINT-HD trial commencing in November 2025. Both drugs came through a collaboration with Ionis Pharmaceuticals, making this a second significant setback for the California-based company in recent days after its Phase III trial of Wainua (eplontersen) in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), developed in collaboration with AstraZeneca, failed to meet its primary endpoint in a Phase III trial.
The debut of the GENERATION HD2 trial in 2022 was considered by some to be a surprising turn of events from Roche. The company had previously halted tominersen’s development in March 2021 after it failed to show evidence of clinical benefit in the Phase III GENERATION HD1 (NCT03761849) study. GENERATION HD2 was underway by early 2023.
Tominersen is an antisense oligonucleotide (ASO) that reduces the production of all forms of the huntingtin protein, including its mutated variant (mHTT).
RG6496 is also an ASO that blocks the production of all forms of the Huntingtin protein responsible for Huntington’s disease.
Roche does still have hope in the Huntington’s disease market, in the form of a gene therapy, RG6662, which it acquired from Spark Therapeutics in 2019 and is in a Phase I/II trial (NCT06826612). The company confirmed this study is ongoing and will continue as planned.
There are companies that are closer to approval, however, with uniQure now in discussions with the US Food and Drug Administration (FDA) about its Huntington’s gene therapy, AMT-130, which, if approved, would be the first therapy indicated for the inherited neurodegenerative disorder. Following a U-turn from the agency, a biologics license application (BLA) filing is anticipated in Q3 2026.
Speaking after uniQure’s data was released in September 2025, managing neurology analyst at GlobalData, Pippa Salter, said: “In a market where the only available therapies are for the symptomatic management of chorea, the efficacy results of AMT-130 are unprecedented. Key opinion leaders previously interviewed by GlobalData consistently highlighted the significant unmet need in the Huntington’s market for a therapy that can modify the disease and slow or prevent progression, with AMT-103 poised to become the first treatment option that meets this need.”
Approximately 75,000 people in the US, Europe, and the UK have the inherited disease, which is fatal within 15 to 20 years of symptom onset.
GlobalData analysis valued the Huntington’s market across the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan) at $300m in 2024, but believes it will reach $3.8bn by 2034.
This is due to a significant lack of approved therapies for the disease currently; however, the analysis predicts a number of pipeline assets will gain approval during the forecast period.
GlobalData is the parent company of Clinical Trials Arena.
