Eplontersen lowered the amyloid protein and still missed its endpoint in heart amyloidosis
The largest transthyretin amyloid cardiomyopathy trial reported to date, CARDIO-TTRansform, gave eplontersen or placebo to 1,432 people. The drug suppressed circulating transthyretin, yet the trial counted 381 cardiovascular events on the drug against 392 on placebo and missed its primary composite goal. A nominally significant benefit appeared only among people not already on background stabiliser therapy.
Science··Midday
Protein fell while the primary goal missed
The CARDIO-TTRansform trial gave eplontersen or placebo every four weeks to 1,432 people with transthyretin amyloid cardiomyopathy at 130 centres in 20 countries; mean age was 72 and 9.4 per cent were women. News-Medical reports this as the largest such trial reported to date. The drug suppressed circulating transthyretin, yet the primary composite of cardiovascular death and recurrent cardiovascular events counted 381 events on the drug against 392 on placebo and did not separate clearly from chance. The findings were presented in a Hot Line session at the ESC Congress 2026.[1], [2]
Background stabiliser use split the outcome
Among people not on background stabiliser therapy at baseline, fewer primary composite events appeared on eplontersen alone than on placebo, reaching nominal significance. Among those already taking a stabiliser, no added benefit showed for the primary composite; 57 per cent of those enrolled were on stabiliser therapy at baseline. The investigators present that split as exploratory. Tolerability matched earlier results.[1], [2]
Disease burden and existing approvals frame the readout
Presenter Mathew Maurer of Columbia University stressed that an estimated 300,000 to 500,000 people worldwide live with transthyretin amyloid cardiomyopathy, an under-recognised cause of heart failure. Eplontersen is an approved RNA-targeted silencer for hereditary transthyretin amyloid polyneuropathy that aims to cut liver transthyretin production. The drug suppressed circulating transthyretin through week 140, consistent with the expected pharmacodynamic effect. Missing the primary goal shows that lowering the protein alone did not clearly cut clinical events in this population.[2], [1]
