Why it matters: The decisions eliminate two of Roche’s three clinical approaches to lowering the toxic huntingtin protein that drives the neurodegenerative disease, for which no disease-modifying treatment is currently approved. Roche communicated the news in a letter to the patient community.
Zoom in: Roche’s phase 2 GENERATION HD2 trial found that tominersen significantly reduced mutant huntingtin and neurofilament light chain, a marker associated with neuronal damage.
Yes, but: The treatment had no meaningful effect on clinical outcomes compared with placebo after 16 months, prompting Roche to end the programme.
Backstory: Roche licensed tominersen from US-based Ionis Pharmaceuticals in 2017. The antisense oligonucleotide had already failed a phase 3 trial in 2021, after patients receiving the more frequent dosing regimen performed worse than those receiving placebo.
- GENERATION HD2 was designed to test whether lower and less frequent doses could benefit younger patients at an earlier stage of the disease.
Meanwhile: Roche has also stopped the phase 1 POINT-HD trial of RG6496, another Ionis-partnered drug, after a longer-term animal study indicated that the antisense drug could not be administered chronically through repeated dosing.
- Only three participants had entered the first-in-human study. Roche said there were no safety concerns associated with the single doses they received.
What remains: Roche is continuing a phase 1/2 trial of RG6662, an experimental gene therapy previously known as SPK-10001.
- The programme came from Spark Therapeutics, the US gene therapy company Roche acquired for $4.3bn in 2019. RG6662 uses an adeno-associated virus vector to deliver genetic material intended to reduce production of the mutant huntingtin protein.
The big picture: The Spark-derived asset now represents Roche’s only remaining clinical Huntington’s programme.
- Competition is also advancing. Dutch biotech uniQure is preparing a US regulatory filing for its Huntington’s gene therapy AMT-130 in the third quarter of 2026.
- UK-based biotech LoQus23 Therapeutics is advancing an oral small molecule targeting MutSβ, a protein complex that has emerged as a central driver of disease progression in Huntington’s disease. The company is aiming to file regulatory submissions to initiate clinical testing later this year.
Reality check: It’s not a good week for Ionis, as its AstraZeneca-partnered drug eplontersen failed to hit the primary endpoint in a phase 3 trial in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).
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