Abstract Aims Eplontersen is an antisense oligonucleotide that suppresses hepatic production of circulating transthyretin (TTR) by targeting TTR mRNA. We present baseline data from an ongoing trial, CARDIO-TTRansform, evaluating eplontersen in patients with TTR amyloidosis with cardiomyopathy (ATTR-CM) and compare findings across previous ATTR-CM trials. Methods and results We evaluated 1432 patients enrolled in CARDIO-TTRansform from March 2020 to July 2023 who received ≥1 dose of study intervention (eplontersen or placebo) and had ≥1 post-baseline measurement. Mean (standard deviation) age was 76.4 (7.1) years; 9.4% were female; 88.8% were White. A total of 211 (14.7%) patients had hereditary/variant ATTR-CM (ATTRv-CM); Val122Ile (p.Val142Ile) was the most common genotype (n=130). Patients spanned New York Heart Association functional classes I (n=192), II (n=997), and III (n=243); 62.6% were National Amyloidosis Centre disease stage 1. Median (interquartile range; IQR) N-terminal pro-B-type natriuretic peptide was 2025 (1296–3465) pg/ml; n=51 measured 8500 pg/ml. Median (IQR) high-sensitivity troponin T was 50 (35‒69) pg/ml and mean left ventricular ejection fraction was 55.7% (9.7%). At baseline, 57.2% were on TTR stabiliser; 18.4% were on sodium-glucose co-transporter-2 inhibitors. Conclusions The baseline characteristics of CARDIO-TTRansform were consistent with previous ATTR-CM trials; however, CARDIO-TTRansform evaluated patients with a wide range of disease severity and receiving the contemporary standard of care for ATTR-CM. Overall, blinded baseline data suggest that CARDIO-TTRansform provides a unique opportunity to determine the clinical benefits of eplontersen in a contemporary setting and in clinically relevant subgroups of patients with ATTR-CM.
Fontana et al. (2026) studied this question.