CAMBRIDGE, United Kingdom, July 9, 2026
AstraZeneca and Ionis Pharmaceuticals have announced results from the Phase III CARDIO-TTRansform trial evaluating Wainua® (eplontersen) in adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The global study did not meet its primary efficacy endpoint of reducing the composite outcome of cardiovascular mortality and recurrent cardiovascular clinical events through 140 weeks compared with placebo. Despite missing the primary endpoint, Wainua demonstrated a favorable safety profile consistent with previous clinical studies and continued to be generally well tolerated. The findings provide valuable scientific insights into the treatment of ATTR-CM and highlight the evolving complexity of managing patients receiving modern standards of care, including transthyretin stabilizer therapies. AstraZeneca and Ionis stated that the complete dataset will undergo further analysis before presentation at the European Society of Cardiology (ESC) Congress 2026, contributing to future research in cardiovascular and rare disease therapeutics.
Largest ATTR-CM Phase III Study Evaluates Wainua with Standard Care
The CARDIO-TTRansform study is the largest Phase III clinical trial conducted in transthyretin-mediated amyloid cardiomyopathy, enrolling 1,432 participants across 130 clinical sites in 20 countries. Patients with hereditary or wild-type ATTR-CM were randomized to receive Wainua 45 mg or placebo by subcutaneous injection every four weeks while continuing available standard of care. Approximately 57% of participants were receiving transthyretin stabilizer therapy at baseline, while an additional 24% initiated stabilizer treatment during the trial, reflecting contemporary clinical practice.
Although adding Wainua to standard therapy did not significantly reduce the combined endpoint of cardiovascular mortality and recurrent cardiovascular events, the investigational therapy maintained a consistent safety and tolerability profile, reinforcing confidence in its established clinical safety. Researchers also observed a prespecified subgroup of patients receiving Wainua monotherapy experienced fewer cardiovascular deaths and recurrent cardiovascular events compared with placebo, producing a nominally significant result, whereas patients already receiving stabilizer therapy showed no measurable treatment benefit.
Subgroup Findings Offer Important Direction for Future Research
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According to Sharon Barr, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, the study was specifically designed to evaluate whether RNA-targeted gene silencing therapy could deliver additional clinical benefit when combined with today’s standard treatment for ATTR-CM. While the primary endpoint was not achieved, the results significantly improve scientific understanding of treatment strategies for this rare, progressive, and often fatal cardiovascular disease. ATTR-CM develops when misfolded transthyretin (TTR) proteins accumulate within the heart, progressively impairing cardiac function and leading to heart failure and increased mortality.
The disease is estimated to affect 300,000 to 500,000 people worldwide, making continued therapeutic innovation a major priority within cardiovascular medicine. AstraZeneca and Ionis confirmed they will perform detailed analyses of the complete clinical dataset to better understand differences observed between treatment subgroups and to guide future development strategies for RNA-targeted medicines.
Wainua Continues to Support AstraZeneca’s RNA Therapeutics Strategy
Wainua (eplontersen) is a once-monthly RNA-targeted silencer designed to reduce production of transthyretin protein in the liver through advanced antisense technology. The therapy is already approved in more than 20 countries for treating hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN), demonstrating its established role in rare disease treatment. Although the CARDIO-TTRansform study did not achieve its primary objective in ATTR-CM, the trial contributes valuable evidence that will inform future clinical development, optimize treatment approaches, and strengthen understanding of RNA-based therapeutics in cardiovascular disease.
The continued collaboration between AstraZeneca and Ionis Pharmaceuticals reflects a long-term commitment to advancing innovative therapies for patients with serious cardiovascular and rare diseases while supporting ongoing progress in precision medicine, RNA therapeutics, and next-generation cardiovascular drug development.
Source: AstraZeneca, Ionis Pharmaceuticals press release
