Talk Bio

AstraZeneca and Ionis’ Wainua (eplontersen) missed the primary endpoint in the 1,432-patient, 140-week CARDIO-TTRansform Phase 3 trial in ATTR-CM. Adding Wainua to standard care did not significantly reduce cardiovascular death plus recurrent cardiovascular events. The result appears driven largely by background stabilizer use: 57% of patients in both arms were already taking a TTR stabilizer at baseline, and another 24% began one during the trial. In the baseline-stabilizer subgroup, Wainua showed no treatment effect. By contrast, the prespecified subgroup receiving Wainua without a stabilizer showed fewer primary-endpoint events, with a nominally significant hazard ratio of about 0.71. However, this subgroup result was not sufficient to rescue the overall trial, and the study was not necessarily powered to establish monotherapy superiority. Later detailed reporting put the overall hazard ratio at about 1.14—roughly a 14% higher rate of cardiovascular mortality or recurrent ev...