The European Society of Cardiology congress in Munich was a consequential meeting for Alnylam Pharmaceuticals (ALNY), as the outlook wavers for its two ATTR-CM drugs following a competitor’s surprise failure in the same heart disease.
Cardiologists and investors learned new details from AstraZeneca (AZN) and Ionis Pharmaceuticals (IONS) on why their drug eplontersen failed to significantly reduce the risk of cardiovascular death or recurrent events compared with a placebo. Top-line results from the Phase 3 CARDIO-TTRansform study were disclosed in July. Eplontersen showed no treatment effect in the majority of participants who were already taking commonly used “stabilizer” drugs as background therapy, the companies said. In a prespecified subgroup not receiving those drugs at baseline, it reduced the risk of cardiovascular death or events by 29 per cent.
The reason for the failure, eplontersen’s inability to deliver cardiovascular benefit on top of a stabilizer, raises awkward questions about the future of silencers. Cardiologists may prefer oral, easily administered stabilizers to injectables, and if a combination does not work, a silencer used after a stabilizer might not either.
Billions of dollars are at stake. Pfizer’s (PFE) Vyndamax, the oldest stabilizer on the market, had sales above $6bn last year, while BridgeBio’s (BBIO) Attruby, the newest, generated more than $400mn in the first half of 2026 and is fast approaching blockbuster status. Amvuttra’s sales across ATTR-CM and a nerve-related condition already exceed $1bn a quarter, yet on its latest earnings call Alnylam surprised investors by cutting its full-year forecast for the drug, citing maturing growth and “normalized” patient demand.