Biogen Reports Phase 2 CELIA Trial Results for Diranersen in Early Alzheimer's Disease

Biogen's Phase 2 CELIA trial of diranersen in early Alzheimer's disease demonstrated cognitive benefits and robust tau pathology reduction at 18 months, supporting plans for Phase 3 development despite missing its primary dose-response endpoint.

Biogen announced detailed Phase 2 CELIA data for diranersen (BIIB080), an investigational antisense oligonucleotide (ASO) targeting microtubule-associated protein tau (MAPT) mRNA, at the Alzheimer's Association International Conference (AAIC) 2026.

The trial did not meet its primary endpoint of establishing a clinical dose response on the Clinical Dementia Rating Sum of Boxes (CDR-SB) at 18 months, as higher doses were not associated with greater slowing of decline.

The 60 mg intrathecal dose administered every six months demonstrated the strongest response, slowing clinical decline compared to placebo by 26% on CDR-SB, 42% on ADAS-Cog13, and 50% on MMSE.

Diranersen demonstrated robust reductions in cerebrospinal fluid (CSF) total tau of 50% to 65% across all doses and reduced brain tau pathology measured via PET imaging, making it the first tau-directed therapy to show both CSF and brain tau reductions in Phase 2.

Unlike therapies that target extracellular tau, diranersen is designed to lower both intracellular and extracellular tau protein by targeting MAPT mRNA.

The data provide Phase 2 proof of concept that reducing tau pathology correlates with measurable slowing of cognitive decline in early Alzheimer's disease.

In 2025, the FDA granted Fast Track designation to diranersen, which provides access to an expedited regulatory pathway and increased FDA interaction as Biogen plans to advance the candidate into confirmatory Phase 3 development.

The positive cognitive signal and biomarker clearance support the viability of RNA-targeted antisense oligonucleotides (ASOs) for central nervous system indications.

The advancement of diranersen into Phase 3 provides competitive read-through to other clinical stage assets utilizing antisense and blood-brain barrier delivery technologies to target tau.

For Ionis Pharmaceuticals, which discovered diranersen and licensed it exclusively to Biogen in 2019, the successful Phase 2 efficacy outcomes validate their underlying discovery platform and position the company for potential regulatory progress and commercial royalties.

The initiation of the confirmatory Phase 3 clinical trial program for diranersen.

Longer-term clinical durability and functional safety results from the ongoing long-term extension study of CELIA.