Roche drops two Huntington’s programmes from Ionis

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).