Roche halts Huntington's phase 3 of Ionis-partnered antisense drug as blockbuster hopes fade

Roche has stopped a phase 3 Huntington’s disease clinical trial after an interim review of the data. The preplanned review found no new safety signals associated with Ionis Pharmaceuticals-partnered antisense drug tominersen, suggesting lack of efficacy may have driven the decision to stop the trial.

Tominersen, also known as IONIS-HTTRx and RG6042, is designed to reduce production of HTT, the protein that in its mutated form drives the rare genetic, progressive condition Huntington’s. HTT is a validated target, but difficulties drugging the protein via traditional modalities means there remains a major unmet need in Huntington’s, leading companies including Ionis to try to come at the problem from a new angle.

Ionis’ work led to a licensing deal with Roche in 2017 and forecasts of $5 billion peak annual sales for antisense therapy tominersen. “Given the unmet medical need, with no therapies approved to slow progression of this rare disease, tominersen was widely acknowledged to be a potential high risk but blockbuster reward asset in Roche's pipeline,” analysts at Jefferies wrote in a note to investors.

Roche is following previously treated patients in the phase 3 but is stopping dosing. An open-label extension is also on pause, but a pharmacokinetic trial—which was temporarily stopped last year  over safety concerns—and a natural history study will continue. Roche will decide on the next steps once it has analyzed the data, but, as it stands, the prospects for tominersen look bleak.

The setback is a blow to both companies, but the size of Roche means it is better equipped than Ionis to take the hit. Shares in Ionis fell 21% after the news as investors digested its implications for the biotech. “As the HD program was viewed as the largest opportunity in late pipeline, this is a major setback, particularly for IONS' neuro franchise, in our view,” analysts at Jefferies wrote.
The failure of tominersen creates a potential opportunity for other developers of Huntington’s drugs. Wave Life Sciences and Takeda are partnered on two antisense therapies that are in phase 1/2 trials. Takeda also recently picked up a preclinical mRNA translation modulator through a deal with Anima Biotech, and Arvinas is exploring the application of its protein degradation platform to the disease.