Form 8-K · Current Report · Filed 2026-07-09

Ionis Pharmaceuticals' Eplontersen Phase 3 Trial Fails to Meet Primary Endpoint

Ionis Pharmaceuticals, Inc. announced on July 9, 2026, that its CARDIO-TTRansform Phase 3 trial for eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) did not meet the primary efficacy endpoint of the composite outcome of cardiovascular (CV) mortality and recurrent CV events up to Week 140 compared with placebo. In a prespecified subgroup analysis of patients treated with eplontersen monotherapy, a nominally significant hazard ratio of 0.71 was observed on the composite outcome of CV mortality and recurrent CV events. However, in patients who were on stabilizer therapy at baseline, no treatment effect was observed. Multiple secondary, imaging, and biomarker analyses favored eplontersen versus placebo, with large and sustained reductions in transthyretin observed. Eplontersen was well tolerated, with a favorable safety profile consistent with previous results. Ionis and AstraZeneca will continue to analyze the full data set, and results will be shared with the scientific community at the European Society of Cardiology Congress in August 2026.