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).