Biogen’s Diranersen Falls Short on Primary Goal Yet Signals a Breakthrough in Tau Targeting

Biogen has announced topline results from the Phase 2 CELIA study (NCT05399888) evaluating diranersen (BIIB080), an investigational antisense oligonucleotide (ASO) therapy for patients with early Alzheimer’s disease. According to the company, the study is the first to show both a reduction in tau pathology and evidence of cognitive benefit in patients with the disease.

The therapy is designed to target tau pathology by reducing the production of tau protein through suppression of microtubule-associated protein tau (MAPT) messenger RNA. Tau accumulation is considered one of the key drivers of neurodegeneration and cognitive decline in Alzheimer’s disease. In 2025, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to diranersen for the treatment of Alzheimer’s disease.

CELIA is a global Phase 2 randomised, double-blind, placebo-controlled, dose-ranging trial assessing the effectiveness, safety, and tolerability of diranersen in patients with early-stage Alzheimer’s disease. The research included 416 individuals experiencing mild cognitive impairment or mild dementia related to Alzheimer’s disease. All individuals participating in CELIA had not previously received anti-amyloid therapy. Three doses of diranersen were administered intrathecally over a 76-week placebo-controlled treatment period: 60 mg every 24 weeks, 115 mg every 24 weeks, and 115 mg every 12 weeks.

The primary endpoint was assessment of dose response for change from baseline on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at Week 76. Secondary and exploratory endpoints included additional clinical, biomarker and imaging measures, including cerebrospinal fluid tau biomarkers and tau positron emission tomography (PET)

According to the company, the study did not meet its primary endpoint. However, pre-specified analyses demonstrated slowing of clinical decline across treatment groups, particularly among participants receiving the lowest dose regimen. Diranersen also demonstrated robust reductions in both CSF tau and tau pathology, as measured by PET, across all studied doses.

These findings were described as consistent with observations from earlier Phase 1b (NCT03186989) studies. The incidence of adverse events (AEs) was comparable across dose groups, with a higher incidence of serious adverse events (SAEs) observed at the highest dose studied.

A long-term extension (LTE) study is still assessing the long-term safety, tolerability, and durability of c in early Alzheimer’s disease

In December 2019, Biogen exercised a license option with Ionis Pharmaceuticals and obtained a worldwide, exclusive, royalty-bearing license to develop and commercialise diranersen. Diranersen was discovered by Ionis.

Priya Singhal, M.D., M.P.H., Executive Vice President and Head of Development at Biogen, said that they have seen an unprecedented and compelling confluence of efficacy and biomarker results from a tau-directed agent in a randomised early Alzheimer’s disease study and are excited by these Phase 2 data to advance diranersen to registrational development.

These findings encourage the company’s focus on developing therapies targeting multiple disease mechanisms. The company also confirmed that detailed results from the CELIA study will be presented at upcoming scientific meetings, including the Alzheimer’s Association International Conference (AAIC) 2026.

References

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 | Biogen

Study Details | NCT05399888 | A Study to Learn About the Safety of BIIB080 Injections and Whether They Can Improve Symptoms of Participants With Mild Cognitive Impairment Due to Alzheimer’s Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age | ClinicalTrials.gov

Ionis partner Biogen announces 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 | Ionis Pharmaceuticals, Inc.