Ionis and AstraZeneca's eplontersen misses primary endpoint in Phase 3 ATTR-CM trial

Ionis Pharmaceuticals and partner AstraZeneca said on July 9, 2026 that the Phase 3 CARDIO-TTRansform trial of eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) did not meet its primary efficacy endpoint of a composite of cardiovascular mortality and recurrent CV clinical events through Week 140 compared with placebo.¹ In this patient population treated with standard of care, including a majority already on a stabilizer, adding eplontersen did not produce a statistically significant benefit.¹

A prespecified subgroup analysis offered a different picture. Among patients treated with eplontersen monotherapy versus placebo, researchers calculated a hazard ratio of 0.71 on the composite CV endpoint that reached nominal significance.¹ By contrast, patients already on stabilizer therapy at baseline showed no treatment effect.¹

Some secondary measures still favored the drug. Across the overall population, several secondary, imaging, and biomarker analyses trended in favor of eplontersen relative to placebo,¹ and the company reported strong knockdown of the target protein consistent with its drug class, describing the safety profile as consistent with earlier data.

The trial, described as the largest enrolled ATTR-CM study to date, included 1,432 participants across 130 sites in 20 countries, randomized evenly to receive either eplontersen 45 mg or placebo by subcutaneous injection every four weeks.¹ Notably, 57% of patients in each arm were on a stabilizer at baseline, with another 24% starting one during the study.¹

Ionis CEO Brett Monia said the company believes the results reflect how ATTR-CM treatment has evolved, with more contemporary patients already on stabilizer drugs.¹ The companies plan further data analysis, with full results expected to be presented at the European Society of Cardiology Congress in August 2026.

WAINUA (eplontersen) is already approved in more than 20 countries for a related indication, the polyneuropathy form of hereditary ATTR amyloidosis. Ionis and AstraZeneca jointly develop and commercialize eplontersen in the U.S., while AstraZeneca holds exclusive rights outside the U.S.¹