The CARDIO-TTRansform Phase III trial1 for AstraZeneca plc (LON:AZN) and Ionis’ Wainua (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 clinical events up to 140 weeks compared with placebo. Wainua was generally well tolerated, with a safety profile consistent with previous results.2
In this contemporary patient population treated with standard of care, including a majority on a stabiliser,3,4 adding Wainua did not provide a statistically significant benefit on the composite outcome of CV mortality and recurrent CV events. In a prespecified subgroup analysis of patients treated with Wainua monotherapy as compared to placebo, fewer primary composite events (CV mortality and recurrent CV events) were observed and this result was nominally significant. In patients who were on stabiliser therapy at baseline, no treatment effect was observed.
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, said: “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.”
CARDIO-TTRansform is a Phase III, multicentre, randomised, double-blinded, placebo-controlled trial1 to evaluate the safety and efficacy of Wainua compared to placebo in participants with ATTR-CM receiving available standard of care: 57% of patients in each arm received a stabiliser treatment at baseline, and a further 24% in each arm initiated a stabiliser during the trial.3
AstraZeneca and Ionis will analyse the full data set to further understand the results, which will be shared with the scientific community at the European Society of Cardiology (ESC) Congress in August 2026.
References:
1. ClinicalTrials.gov. CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM). Available at: https://clinicaltrials.gov/study/NCT04136171. Accessed July 2026.
2. AstraZeneca 2023. Wainua (eplontersen) granted first-ever regulatory approval in the US for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis. Available at: https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html. Accessed July 2026.
3. Maurer MS, et al. Design and baseline characteristics of the CARDIO-TTRansform phase 3 randomised controlled trial of eplontersen for participants with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Presented at: Heart Failure Congress 2026. Heart Failure Congress 2026; 2026 9-12 May 2026; Barcelona, Spain.
4. Masri A, et al. Rationale and Design of CARDIO-TTRansform, a Phase 3 Tr
