Eplontersen is being evaluated in the fully enrolled CARDIO-TTRansform Phase 3 trial of 1432 participants to assess its efficacy on cardiovascular outcomes in transthyretin amyloid cardiomyopathy.
RCT (n=1,432)
Double-blind
1:1
Does eplontersen reduce cardiovascular mortality and recurrent clinical cardiovascular events in patients with transthyretin amyloid cardiomyopathy?
CARDIO-TTRansform is a fully enrolled Phase 3 trial designed to evaluate whether eplontersen improves cardiovascular outcomes in patients with transthyretin amyloid cardiomyopathy.
BACKGROUND: messenger RNA to reduce the production of circulating TTR. METHODS: CARDIO-TTRansform is a Phase 3, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of eplontersen in transthyretin amyloidosis with cardiomyopathy. Key inclusion criteria include histological evidence of amyloid deposits or grade 2 to 3 cardiac uptake on cardiac scintigraphy in the absence of plasma cell dyscrasia, New York Heart Association class I-III, and end-diastolic interventricular septum thickness >12 millimeters. Participants were randomized 1:1 to receive eplontersen 45 mg or placebo, administered subcutaneously every 4 weeks for up to 140 weeks, followed by a 20-week post-treatment evaluation period or open-label extension. Participants received locally available standard of care, including unrestricted use of TTR stabilizers. The primary end point is a composite of cardiovascular mortality and recurrent clinical cardiovascular events through 140 weeks. Secondary end points, in order of testing hierarchy, include changes from baseline in 6-minute walk distance and Kansas City Cardiomyopathy Questionnaire overall summary score, recurrent cardiovascular events, all-cause mortality, the primary end point in the patient subgroup receiving stabilizers at baseline, and cardiovascular mortality. Echocardiography was performed in all participants, with cardiovascular magnetic resonance imaging and technetium scintigraphy in a subset. CONCLUSIONS: CARDIO-TTRansform is fully enrolled, with 1432 randomized participants who were dosed with study drug or placebo. As the largest transthyretin amyloidosis with cardiomyopathy study to date, it will evaluate whether eplontersen improves cardiovascular outcomes in patients receiving locally available standard of care, including TTR stabilizers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136171. URL: http://ClinicalTrialsRegister.eu; Unique identifier: EudraCT number 2019-002835-27.
AstraZeneca and Ionis announced on July 9, 2026, that their pivotal trial of eplontersen did not reduce cardiovascular events in patients with ATTR-cardiomyopathy, a significant negative result in a closely watched disease area.
Masri et al. (2026) conducted an RCT in Transthyretin amyloidosis with cardiomyopathy (n=1,432). Eplontersen vs. Placebo was evaluated on Composite of cardiovascular mortality and recurrent clinical cardiovascular events through 140 weeks. Eplontersen is being evaluated in the fully enrolled CARDIO-TTRansform Phase 3 trial of 1432 participants to assess its efficacy on cardiovascular outcomes in transthyretin amyloid cardiomyopathy.