BIOBRIEF
Eplontersen, an RNA silencing drug for a fatal inherited heart disease, missed its main goal at the European Society of Cardiology's annual meeting, sharpening questions for Alnylam's rival program.
AstraZeneca and Ionis's once-monthly eplontersen flunked the Phase 3 CARDIO-TTRansform trial in transthyretin amyloid cardiomyopathy (ATTR-CM), missing the primary efficacy endpoint in a Hot Line session at the European Society of Cardiology's annual congress in Munich on Thursday.
Eplontersen is an RNA-targeting "silencer" that lowers the body's production of the transthyretin protein at its source. ATTR-CM is a progressive, often-inherited disease in which misfolded copies of that protein pile up in the heart muscle, stiffening it and driving recurrent heart failure. Dr. Mathew Maurer of Columbia University Irving Medical Center, who presented the results, put the affected population at an estimated 300,000 to 500,000 people worldwide.
The negative readout lands on Alnylam's competing TTR-silencer program, which uses the same underlying mechanism (vutrisiran) and is closing in on its own ATTR-CM readout from the HELIOS-B trial. Alnylam's drug is already approved in the United States and Europe for the nerve-related form of the same disease, and the two companies have been running a parallel class-versus-class race for the larger heart indication.
The CARDIO-TTRansform result does not, on its own, settle that contest. ESC 2026 is hosting 59 late-breaking pivotal trial readouts, and HELIOS-B is one of the few that can now directly test whether the mechanism itself was the problem or whether trial design, population, or endpoint set the bar wrong.