Ionis Pharmaceuticals said its Phase 3 Cardio-TTRansform study of eplontersen in transthyretin-mediated amyloid cardiomyopathy missed its main goal, even as the company pointed to favorable signals in several follow-on analyses.
The trial, which enrolled 1,432 patients across 130 sites in 20 countries, tested eplontersen against placebo in adults receiving standard of care. The primary endpoint was a composite of cardiovascular mortality and recurrent cardiovascular events through week 140. Ionis said the study did not show a statistically significant benefit in the overall population.
A prespecified subgroup analysis told a different story for patients on eplontersen monotherapy: that group showed a nominally significant hazard ratio of 0.71 on the same composite endpoint. By contrast, patients already on stabilizer therapy at baseline showed no treatment effect.
The background treatment mix was a major factor in the study. Ionis said 57% of patients in each arm were already on a stabilizer at baseline, and another 24% in each arm started a stabilizer during the trial.
Beyond the missed primary endpoint, Ionis said multiple secondary, imaging and biomarker measures favored eplontersen over placebo. The company also said the drug produced large and sustained reductions in transthyretin, and that its safety profile remained favorable and consistent with prior results.
The company described Cardio-TTRansform as the largest enrolled ATTR-CM trial to date. It said it will continue analyzing the full data set and plans to present results to the scientific community at the European Society of Cardiology congress in August 2026. Following these announcements, the company's shares moved -23.92%, and are now trading at a price of $64.255. For the full picture, make sure to review IONIS PHARMACEUTICALS INC's 8-K report.
