MUNICH — Eplontersen, a drug already approved for polyneuropathy caused by transthyretin (TTR) amyloid deposits, does not protect against cardiovascular events or death associated with TTR-mediated amyloid cardiomyopathy (ATTR-CM), according to a phase 3 trial.
With up to 140 weeks of follow-up, the rate of the primary endpoint of cardiovascular mortality or events was 11% lower in the eplontersen than in the placebo group (rate ratio [RR], 0.89), but the difference was nonsignificant (P=.28), said principal investigator Mathew S. Maurer, MD, director of the Cardiac Amyloidosis Program at Columbia University in New York City.
The failure to show clinical benefit was seen despite a 60% reduction in trough serum TTR levels at the first analysis. This reduction at week 13 persisted over time with a slight climb in TTR levels with placebo, producing a mean placebo-corrected percent change for eplontersen of 77.2% from baseline at week 140.
The results of the CARDIO-TTRansform trial were presented at the European Society of Cardiology (ESC) Congress 2026 and simultaneously published in The New England Journal of Medicine.
By the Numbers
In the trial, 1432 patients with ATTR-CM were randomized to eplontersen, an antisense oligonucleotide that targets TTR mRNA, or placebo at 130 centers in 20 countries. Adults were eligible for enrollment if they had an interventricular septum thickness ≥ 12 mm, a history of heart failure with a New York Heart Association class of III or less, and an N-terminal pro-B-type natriuretic peptide ≥ 600 pg/mL.
In the experimental group, a subcutaneous 45-mg dose of eplontersen was administered every 4 weeks.
By the end of the study, 29.4% of the 715 patients in the eplontersen group and 32.2% of the 717 patients in the placebo group had died of a cardiovascular cause or had one predefined cardiovascular event. Those events included myocardial infarction, hospitalization for heart failure, stroke, transient ischemic attack,