CARDIO-TTRansform Phase III trial update for Wainua in adults with transthyretin-mediated amyloid cardiomyopathy

The Phase III CARDIO-TTRansform trial examining AstraZeneca and Ionis’ Wainua (eplontersen) in patients with transthyretin-mediated amyloid cardiomyopathy failed to reach its primary efficacy endpoint, which measured a composite outcome of cardiovascular mortality and recurring cardiovascular clinical events over up to 140 weeks against placebo. Wainua was broadly well tolerated throughout, with a safety profile in keeping with earlier findings.

In a patient population receiving contemporary standard of care, the majority of whom were already taking a stabiliser, the addition of Wainua did not produce a statistically significant improvement on the composite measure of cardiovascular mortality and recurring cardiovascular events. A prespecified subgroup analysis of patients receiving Wainua without a stabiliser did show fewer primary composite events compared to placebo, with the result reaching nominal significance. Among those who had been on stabiliser therapy at the outset of the trial, no treatment effect was detected.

“The CARDIO-TTRansform trial was designed to examine the role of Wainua, a gene silencer treatment, on top of today’s standard of care in reducing recurring cardiovascular events and mortality. Although the trial did not meet its primary objective, we believe the results support greater scientific understanding of treatment approaches for the hundreds of thousands of patients worldwide suffering from this progressive and often fatal condition,” said Sharon Barr, Executive Vice President, BioPharmaceuticals R&D.

CARDIO-TTRansform is a Phase III multicentre, randomised, double-blinded, placebo-controlled study designed to assess the safety and efficacy of Wainua against placebo in participants with transthyretin-mediated amyloid cardiomyopathy who were receiving available standard of care. At baseline, 57% of participants in each arm were on a stabiliser treatment, with a further 24% in each arm commencing a stabiliser at some point during the trial.

AstraZeneca and Ionis will conduct a thorough analysis of the complete dataset to deepen understanding of the findings, which are set to be presented to the wider scientific community at the European Society of Cardiology Congress in August 2026.

---

---

Related Topics and Keywords

CARDIO-TTRansform, CARDIO-TTRansform Phase III trial, transthyretin-mediated amyloid cardiomyopathy, Wainua, Wainua (eplontersen)