Eplontersen fails to improve cardiovascular outcomes in ATTR-CM trial

The phase 3 CARDIO-TTRansform clinical trial found that adding eplontersen to standard therapy did not significantly reduce cardiovascular mortality or recurrent cardiovascular events in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The results, presented at the European Society of Cardiology Congress and published in The New England Journal of Medicine, involved 1,432 patients across 130 centers in 20 countries.

While eplontersen successfully suppressed circulating serum transthyretin levels, the primary composite endpoint—combining cardiovascular death and recurrent events—did not show a statistically significant difference compared to a placebo over 140 weeks. Many participants in the study were already receiving existing ATTR-CM treatments, such as TTR stabilizers and standard heart failure medications like SGLT2 inhibitors.

Eplontersen is currently approved for polyneuropathy of hereditary TTR-mediated amyloidosis but lacks an indication for ATTR-CM. This outcome contrasts with other therapies like vutrisiran, which met its primary endpoints in previous trials.