The CARDIO-TTRansform trial investigating eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy did not meet its primary efficacy endpoint, according to results presented in a Hot Line session at ESC Congress 2026.
Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease characterized by misfolded transthyretin (TTR) amyloid deposits in the heart muscle. The deposits can lead to reduced cardiac function, worsening heart failure symptoms and recurrent cardiovascular events.
"ATTR-CM is an underrecognized cause of heart failure," explained presenter Dr. Mathew Maurer from Columbia University Irving Medical Center, New York. "With an estimated 300,000 to 500,000 people living with ATTR-CM worldwide, greater awareness, earlier diagnosis and appropriate targeted treatment are critical to improving outcomes and quality of life for patients," he said.
Eplontersen, a once-monthly RNA-targeted silencer designed to reduce TTR production by the liver, is approved for the treatment of hereditary/variant TTR amyloid polyneuropathy. The CARDIO-TTRansform trial investigated the efficacy and safety of eplontersen in patients with ATTR-CM.
This was a double-blind Phase III trial conducted at 130 centers in 20 countries worldwide. A total of 1,432 patients with wild-type or hereditary ATTR-CM who were receiving available standard care were enrolled. Participants were randomized (1:1) to receive eplontersen 45 mg or placebo by subcutaneous injection every four weeks. The mean age of the study population was 72, and 9.4% were women.
