Signal CARDIO-TTRansform phase III trial of eplontersen misses primary endpoint at ESC Congress 2026

Summary

The CARDIO-TTRansform phase III trial, presented in a Hot Line session at ESC Congress 2026 in Munich on August 28, did not meet its primary efficacy endpoint. The double-blind trial enrolled 1,432 patients with wild-type or hereditary transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) across 130 centers in 20 countries, all already receiving standard-of-care stabiliser therapy. Through 140 weeks, the composite rate of cardiovascular mortality and recurrent cardiovascular events did not differ significantly between eplontersen and placebo (rate ratio 0.89, 95% CI 0.73-1.09, P=.277). Subgroup findings suggested background stabiliser use influenced the result: patients co-administered a stabiliser showed no clear benefit, while patients not receiving a stabiliser had fewer primary endpoint events on eplontersen. The drug's safety profile remained favorable and consistent with earlier trial data. The same ESC Congress days also featured results from the CMR GUIDE, aficamten, and POET-II trials, plus the first ESC guidelines on cardiovascular disease and chronic kidney disease.