Biogen IncPhase 2 trial missed primary endpoint with unexpected inverse dose response, raising doubts about drug's efficacy and path forward.

Biogen shares fell nearly 9% after the Phase 2 CELIA readout of its Alzheimer's therapy diranersen showed an unexpected inverse dose response. The trial missed its primary endpoint of a dose-dependent response on the CDR-SB scale, with the lowest 60 mg dose delivering a 26% slowing of cognitive decline while higher doses showed diminishing returns. Diranersen achieved a 50% to 65% reduction in cerebrospinal fluid total tau and demonstrated 0% ARIA, a clean safety profile that contrasts with existing anti-amyloid therapies. Analysts are divided on whether the 26% slowing is competitive with the 27% to 29% benchmark set by Leqembi and Kisunla, and management's inability to explain the dosing paradox drove the sell-off. Biogen plans to advance the drug to Phase 3, but must resolve the dosing mystery and refine patient criteria.
Biogen IncPhase 2 trial missed primary endpoint with unexpected inverse dose response, raising doubts about drug's efficacy and path forward.