Topline Phase 2 CELIA Results Show Diranersen Misses Primary End Point in Early Alzheimer Disease

In a new company update, Biogen announced topline findings from the phase 2 CELIA study (NCT05399888) evaluating diranersen (BIIB080), an investigational antisense oligonucleotide therapy targeting tau, in patients with early Alzheimer disease (AD). Finding showed that the study did not meet its primary end point, measured as dose response for change from baseline on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at week 76.¹

Despite this, pre-specified analyses showed slowing of clinical decline across all studied dose groups of diranersen, with the most notable effects observed among participants receiving the lowest dose tested, 60 mg administered every 24 weeks. Treatment was also associated with reductions in cerebrospinal fluid tau and tau pathology measured by positron emission tomography imaging across all evaluated doses, which were assessed as secondary and exploratory outcomes, with reductions maintained throughout the dosing period.

“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,” Jeffrey Cummings, MD, ScD, professor of brain sciences at the University of Nevada, Las Vegas, said in a statement.¹ “I am encouraged by these promising data, which represent meaningful progress toward advancing a new mechanism of action and shaping the next generation of Alzheimer’s disease treatments.”

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CELIA is a global phase 2 randomized, double-blind, placebo-controlled, dose-ranging trial evaluating the efficacy, safety, and tolerability of diranersen in early AD. The study enrolled 416 participants with mild cognitive impairment because of AD or mild AD dementia, all of whom were naïve to prior antiamyloid therapy. Participants received intrathecal diranersen at doses of 60 mg every 24 weeks, 115 mg every 24 weeks, or 115 mg every 12 weeks during a 76-week placebo-controlled treatment period.The company noted that an ongoing long-term extension study is continuing to evaluate the long-term safety, tolerability, and durability of diranersen in early AD.

“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,” Priya Singhal, MD, MPH, executive vice president and head of development at Biogen, said in a statement.¹ “We are excited by these Phase 2 data, which give us the confidence to advance diranersen to registrational development. We look forward to engaging with regulators and the broader Alzheimer’s disease community on next steps. I would like to thank the patients, families, investigators, and study teams who participated in this pioneering study.”

Safety and tolerability findings from CELIA were reported to be generally consistent with the phase 1b study (NCT03186989) and with the known safety profile of diranersen to date.² The incidence of adverse events (AEs) was reported to be comparable across treatment groups. However, investigators observed a higher incidence of serious AEs among participants receiving the highest dose studied. Overall, the company noted that the phase 2 CELIA findings represent the first evidence from a randomized phase 2 study of a tau-directed therapy demonstrating effects on biomarkers alongside measures of clinical benefit in early AD.

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REFERENCES
1. Topline Results from Phase 2 CELIA Study of Diranersen (BIIB080): First Study to Show Reduction in Tau Pathology and Cognitive Benefit in Patients with Early Alzheimer’s Disease. News release. May 14, 2026. Accessed May 14, 2026. https://investors.biogen.com/news-releases/news-release-details/topline-results-phase-2-celia-study-diranersen-biib080-first
2. Ziogas N, Wu S, Li Y, et al. Exploratory clinical outcomes from BIIB080 (MAPT ASO) Phase 1b multiple ascending dose and long-term extension study in mild Alzheimer’s disease. Presented at: CTAD Conference 2023; October 24-27; Boston, MA. LB09.