Eplontersen did not significantly reduce the combined risk of cardiovascular death and recurrent cardiovascular events in adults with transthyretin amyloid cardiomyopathy (ATTR-CM) when added to current standard treatments, according to results from the Phase III CARDIO-TTRansform trial published recently in a press release from AstraZeneca, the drug’s maker.
For patients, this means the therapy, while generally safe, is not expected to improve outcomes when layered on top of commonly used stabilizer medications.
“The CARDIO-TTRansform trial was designed to examine the role of [eplontersen], a gene silencer treatment, on top of today’s standard of care in reducing recurring cardiovascular events and mortality,” explained Sharon Barr, an executive at AstraZeneca, in the press release.
The global study followed patients for up to 140 weeks and compared eplontersen (also called Wainua) with a placebo. Most participants were already receiving standard of care treatment, and 57% were on a transthyretin stabilizer at the start, with another 24% beginning one during the trial. In this real-world–like setting, adding eplontersen did not produce a statistically significant reduction in cardiovascular mortality or repeated cardiovascular complications.
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However, a prespecified subgroup analysis showed a different signal. Among patients who received eplontersen alone without a stabilizer, fewer cardiovascular-related deaths or repeated complications occurred compared with those who took a placebo; however, these results didn’t provide clear evidence that eplontersen was responsible for the differences between these groups. Moreover, patients already taking stabilizers did not appear to gain additional benefit from adding eplontersen.
The trial enrolled 1,432 participants across 130 sites in 20 countries, making it the largest study conducted in ATTR-CM to date. Participants were randomly assigned to receive either eplontersen 45 mg or placebo as a subcutaneous injection every four weeks. Secondary measures included physical function and quality of life, such as distance in a 6-minute walk test and symptom burden scores.
ATTR-CM is caused by the buildup of misfolded transthyretin protein in the heart. This leads to stiffening of the heart muscle and reduced ability to pump blood.
Eplontersen is an RNA-targeting therapy designed to reduce production of transthyretin in the liver, and is already approved for hereditary transthyretin amyloidosis with polyneuropathy — the version of ATTR that affects the nerves.
While the CARDIO-TTRansform results do not support its use on top of stabilizers for ATTR-CM, further analyses are ongoing. Full findings are expected to be presented at the European Society of Cardiology Congress in August 2026, which may help clarify how different treatment strategies can be better tailored for patients.
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