Biogen's Tau-Targeting Alzheimer's Drug Shows Promise Despite Missing Primary Endpoint in Phase 2 Study
核心洞察
Biogen's diranersen (搜索) (BIIB080) demonstrated robust reductions in tau pathology and slowing of cognitive decline across all doses in the Phase 2 CELIA study, marking the first randomized study of a tau-directed therapy to show both biomarker impact and cognitive benefit in early Alzheimer's disease.
The study failed to meet its primary endpoint of dose response on the Clinical Dementia Rating-Sum of Boxes at Week 76, with the lowest dose (60 mg every 24 weeks) showing the best cognitive outcomes.
The antisense oligonucleotide therapy showed a safety profile consistent with earlier studies, and Biogen plans to advance diranersen (搜索) to registrational development based on these compelling results.
Biogen Inc. announced compelling topline results from the Phase 2 CELIA study evaluating diranersen (搜索) (BIIB080), an investigational antisense oligonucleotide therapy targeting tau, in individuals with early Alzheimer's disease. The study provides the first evidence from a randomized Phase 2 trial of a tau-directed therapy demonstrating both robust biomarker impact and cognitive benefit in early Alzheimer's disease, though it failed to meet its primary endpoint.
Mixed Results with Promising Therapeutic Signals
The CELIA study, an 18-month Phase 2 randomized, placebo-controlled, dose-ranging study, enrolled 416 participants with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia. While the study did not meet its primary endpoint assessing dose response for change from baseline on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at Week 76, pre-specified analyses of cognitive endpoints demonstrated slowing of clinical decline across all studied doses, particularly at the lowest dose of 60 mg administered every 24 weeks.
"In CELIA, we believe we have seen an unprecedented and compelling confluence of efficacy and biomarkers results from a tau-directed agent in a randomized early Alzheimer's disease study," said Priya Singhal, M.D., M.P.H., Executive Vice President and Head of Development at Biogen. "We are excited by these Phase 2 data, which give us the confidence to advance diranersen (搜索) to registrational development."
Robust Biomarker Reductions Across All Doses
Diranersen (搜索) demonstrated robust reductions in both cerebrospinal fluid (CSF) tau and tau pathology, as measured by positron emission tomography (PET), across all studied doses. These reductions were maintained throughout the dosing period and were generally consistent with those observed in the Phase 1b study. The study evaluated three doses administered intrathecally: 60 mg every 24 weeks, 115 mg every 24 weeks, and 115 mg every 12 weeks.
The counterintuitive finding that the lowest dose showed the best cognitive outcomes contributed to the study's failure to demonstrate a clear dose response, which was the primary endpoint. This pattern led to mixed results despite the promising therapeutic signals observed across multiple measures.
First-in-Class Mechanism Targeting Tau Production
Diranersen (搜索) represents a first-in-class investigational antisense oligonucleotide designed to reduce the production of tau protein at its source in early Alzheimer's disease. Unlike many investigational approaches that have focused on targeting extracellular tau, diranersen is designed to reduce both extracellular and intracellular tau by targeting microtubule-associated protein tau (MAPT (搜索)) mRNA.
"The CELIA topline results represent an important advance for the field, providing the first evidence that reducing tau, a hallmark of Alzheimer's disease closely associated with neurodegeneration and cognitive decline, may meaningfully impact disease progression," said Dr. Jeff Cummings, Professor of Brain Sciences at the University of Nevada, Las Vegas.
Safety Profile Consistent with Earlier Studies
The safety and tolerability profile of diranersen (搜索) across all studied doses was generally consistent with the Phase 1b study. The incidence of adverse events was comparable across dose groups, with a higher incidence of serious adverse events observed at the highest dose studied. All participants enrolled in CELIA had not previously received anti-amyloid therapy.
Regulatory Recognition and Next Steps
In 2025, the U.S. Food and Drug Administration granted Fast Track designation to diranersen (搜索) for the treatment of Alzheimer's disease. Biogen obtained a worldwide, exclusive, royalty-bearing license to develop and commercialize diranersen from Ionis Pharmaceuticals (搜索) in December 2019, after exercising a license option.
The company plans to present detailed data at the Alzheimer's Association International Conference (AAIC) 2026 and other upcoming scientific congresses. An ongoing long-term extension study is continuing to evaluate the long-term safety, tolerability and durability of diranersen (搜索) in early Alzheimer's disease.
The CELIA results mark a significant milestone in Alzheimer's research, as tau accumulation forms intracellular tangles that contribute to neurodegeneration and cognitive decline, representing a key pathological hallmark of the disease alongside amyloid plaques.