Baseline characteristics of patients with transthyretin amyloidosis with cardiomyopathy in the CARDIO-TTRansform trial of eplontersen

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.