Roche ended development on two Huntington’s disease gene-silencing programs after disappointing efficacy and a separate safety signal. The company said it is discontinuing the Phase 2 trial of tominersen (Ionis-partnered) and stopping an early-stage RG6496 program after animal data raised concerns about chronic dosing. Roche’s patient-partnership communication states tominersen did not meet efficacy objectives in its trial, despite safety and biomarker target engagement. For RG6496, Roche said a nonclinical finding indicated the compound “cannot be given chronically with repeated doses,” prompting early termination. Roche said its Phase 1/2 Huntington’s gene therapy candidate RG6662 remains ongoing as planned. The decision adds pressure to the Huntington’s pipeline after years of setbacks for antisense approaches targeting huntingtin. From an industry standpoint, the move underscores how survivability and functional endpoints—and the ability to sustain dosing—continue to be decisive gating factors for Huntington’s therapies beyond target binding and short-term biomarkers.