Same Mechanism, Different Trial: How the FDA Rejected Patisiran but Approved Vutrisiran
Alnylam's two siRNA drugs hit the same liver target. One failed an FDA review in 2023. Two years later the other was approved for both forms of ATTR amyloidosis. The mechanism didn't change. The trial design did.
In September 2023 an FDA advisory committee voted 9-3 that patisiran's benefit supported approval for cardiac ATTR amyloidosis. The FDA rejected it anyway. Eighteen months later it approved vutrisiran — a near-identical Alnylam siRNA against the same liver target — for both forms of ATTR at once. Patisiran's APOLLO-B was 360 patients, 12 months, a six-minute-walk endpoint (+14.7 m, p=0.0162) with a secondary composite that missed at a win ratio of 1.27. Vutrisiran's HELIOS-B was 655 patients, up to 36 months, a hard mortality-plus-CV-events composite cut by 28%. Same mechanism, opposite verdicts — the molecule never changed, the trial did.