AstraZeneca said its antisense drug Wainua (eplontersen) failed to beat placebo in a Phase 3 study in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a pivotal readout partnered with Ionis Pharmaceuticals. The failure centers on the Cardio-TTRansform trial’s inability to demonstrate a significant reduction in cardiovascular death and recurrent cardiovascular events, despite sustained transthyretin-lowering consistent with gene-silencing biology. The negative result reshapes competitive expectations for ATTR-CM therapies and adds pressure on remaining mechanisms in the cardiomyopathy pipeline as companies and investors refocus on next-up late-stage assets.