AstraZeneca’s partnered gene-silencing therapy Wainua (eplontersen) missed its primary goal in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), adding pressure to reshape the company’s late-stage cardiovascular strategy. In the Phase 3 Cardio-TTRansform study, the treatment did not outperform placebo on cardiovascular mortality and recurrent cardiovascular events. Despite reported large and sustained reductions in transthyretin levels consistent with the drug’s intended mechanism, investigators did not see a clinical benefit signal strong enough to move outcomes. Ionis Pharmaceuticals, Wainua’s partner, also faced market impact on the data release. The failure comes at a time when the ATTR-CM landscape is increasingly competitive, with investors and analysts likely to refocus on other TTR-lowering approaches as late-stage readouts continue to define differentiation.