BioCentury
ARTICLE | Product Development

Diranersen’s inverse dose response complicates Biogen’s Phase III path

Lowest dose produced strongest clinical benefit despite smaller biomarker effects, raising questions about dose selection and tau PET as a surrogate endpoint

July 15, 2026 1:22 AM UTC

The shakiest ground for Biogen’s Phase III bet on its anti-tau therapy diranersen may be the disconnect between its dose-dependent biomarker response and its inverse clinical dose response: the strongest clinical benefit emerged at the lowest dose, in the study’s smallest and least statistically powered treatment arm.

The pattern also raises a pointed question for the field: whether tau PET, still an unproven candidate as a surrogate endpoint, can be trusted as a stand-in for clinical benefit...