Roche and Ionis announced the end of two Huntington’s disease programs, including the Ionis-partnered antisense therapy tominersen, after trials missed efficacy goals. Roche said the Phase 2 GENERATION HD2 study did not achieve its primary objective despite target engagement, while a second prospect (RG6496) was stopped after an animal safety signal. In a separate but related cardiometabolic blow, AstraZeneca and Ionis reported a Phase 3 failure for eplontersen (Wainua) in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), with no improvement versus placebo on cardiovascular death and clinical events. AstraZeneca and Ionis shares moved sharply downward on the news. Across both programs, the companies emphasized data-driven decisions and pointed to ongoing alternatives, but the cancellations reduce pipeline confidence in antisense strategies for neurodegeneration and amyloid cardiomyopathy. For investors and patients, the twin setbacks underscore how even biomarker-consistent gene-silencing effects may not translate into clinical endpoints, particularly in late-stage, progressive disease settings.