Wainua (eplontersen) - (CARDIO-TTRansform)

July 8, 2026: Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) and AstraZeneca reported that the Phase 3 CARDIO-TTRansform trial of eplontersen in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) did not meet its primary endpoint, a composite of cardiovascular mortality and recurrent cardiovascular clinical events through Week 140 versus placebo. In this standard-of-care population (57% on a TTR stabilizer at baseline; an additional 24% initiated a stabilizer during the trial), adding eplontersen did not provide a statistically significant benefit.

In a prespecified subgroup, eplontersen monotherapy versus placebo showed a nominally significant hazard ratio of 0.71 on the primary composite endpoint; no treatment effect was seen in patients on stabilizer therapy at baseline. Secondary, imaging, and biomarker analyses in the overall population favored eplontersen, and large, sustained transthyretin reductions were observed. Safety was described as favorable and consistent with prior results.

The companies said they will continue analyzing the full dataset and plan to present results at the European Society of Cardiology (ESC) Congress in August 2026.