Biogen Reports Positive Phase 2 Results For Diranersen And Plans To Advance Alzheimer's Therapy To Phase 3

Biogen Inc. has announced new results from its Phase 2 CELIA study evaluating diranersen, an investigational antisense oligonucleotide (ASO) therapy designed to target tau, one of the key proteins involved in Alzheimer's disease. The findings were presented at the Alzheimer's Association International Conference (AAIC) 2026 and build on previously released topline results. The study showed encouraging clinical benefits along with strong biomarker improvements, providing Phase 2 proof of concept for diranersen's tau-targeting approach. Based on these results, Biogen plans to move the therapy into Phase 3 clinical development.

Professor Cath Mummery, Professor of Clinical Neurology at the UCL Queen Square Institute of Neurology and Consultant Neurologist at University College London Hospitals NHS Foundation Trust, said the CELIA results provide some of the strongest evidence so far that reducing tau pathology can lead to meaningful clinical improvements in patients with Alzheimer's disease. She noted that both the reduction in tau levels and the observed cognitive benefits rank among the most promising findings reported in Alzheimer's drug development and support advancing diranersen into Phase 3 studies.

Priya Singhal, M.D., M.P.H., Executive Vice President and Head of Development at Biogen, said the clinical, biomarker, and safety data presented at AAIC demonstrate proof of concept for diranersen's novel mechanism of reducing tau and translating that effect into measurable clinical benefit. She added that if these findings are confirmed in Phase 3 trials, diranersen could become an important new treatment option targeting one of the major underlying causes of Alzheimer's disease. She also emphasized the urgent need for new therapies that address the complexity of the disease and said Biogen looks forward to working closely with regulatory authorities and the Alzheimer's community as development continues.

The study showed that diranersen produced clinical benefits across all dose levels evaluated over an 18-month treatment period. Improvements were consistently observed across several important measures of cognition, daily functioning, and disease progression, including the Clinical Dementia Rating Sum of Boxes (CDR-SB), ADAS-Cog13, Mini-Mental State Examination (MMSE), modified Integrated Alzheimer's Disease Rating Scale (iADRS), and Alzheimer's Disease Composite Score (ADCOMS).

Among the different dosing groups, the strongest results were seen with the 60 mg dose administered intrathecally once every six months. Compared with placebo, this dose slowed clinical decline by 26% on CDR-SB, 42% on ADAS-Cog13, 50% on MMSE, 30% on modified iADRS, and 23% on ADCOMS after 18 months. Most of these improvements achieved nominal statistical significance when compared with placebo.

The two 115 mg dosing regimens also demonstrated clinical benefits. Patients receiving 115 mg every six months experienced slower disease progression compared with placebo, including a 14% reduction in decline on CDR-SB, 32% improvement on ADAS-Cog13, 34% improvement on MMSE, 29% improvement on modified iADRS, and 21% improvement on ADCOMS. Patients receiving 115 mg every three months also showed positive effects, including a 9% reduction in decline on CDR-SB, 29% improvement on ADAS-Cog13, 38% improvement on MMSE, 18% improvement on modified iADRS, and 7% improvement on ADCOMS.

Although no meaningful difference from placebo was observed on the ADCS-ADL-MCI scale, which measures activities of daily living, researchers noted that functional improvements measured through the functional components of the CDR-SB consistently favored diranersen across all treatment groups. The ongoing long-term extension study will continue to evaluate whether longer treatment durations produce greater improvements in daily functioning.

The CELIA study was specifically designed to determine whether higher doses of diranersen would provide greater clinical benefit using CDR-SB at 18 months as the primary endpoint. However, this dose-response relationship was not observed, meaning the study did not meet its predefined primary endpoint. Despite this, the overall clinical and biomarker findings supported continued development of the therapy.

In addition to the clinical results, diranersen demonstrated strong biological activity by significantly reducing total tau protein levels in cerebrospinal fluid (CSF). Across all dose groups, average CSF total tau levels declined by 50% to 65% from baseline. In a tau PET imaging substudy involving 131 participants, reductions in tau accumulation were also observed across all evaluated brain regions and dose levels. According to Biogen, diranersen is the first tau-directed therapy to demonstrate reductions in both CSF total tau and brain tau pathology measured by PET imaging in a Phase 2 clinical study.

The treatment also showed a favorable safety profile. During the placebo-controlled portion of the study, most reported side effects were mild to moderate in severity, were not considered serious, and rarely led to treatment discontinuation or withdrawal from the trial. The most commonly reported adverse events included procedural pain related to lumbar puncture, post-lumbar puncture syndrome, and temporary episodes of confusion. Most cases of confusion occurred within a few days after dosing and resolved within one week. More than 90% of participants who completed the placebo-controlled phase chose to continue into the long-term extension study.

Because diranersen targets tau rather than amyloid, researchers do not expect it to cause amyloid-related imaging abnormalities (ARIA), a safety concern associated with some amyloid-targeting Alzheimer's therapies. The findings from the CELIA study were consistent with this expectation, as no unexpected ARIA-related safety signals were observed.

The trial enrolled a patient population representative of individuals with early Alzheimer's disease. Participants had an average age of 68 years, 51% were women, 60% had mild cognitive impairment, and 40% had mild Alzheimer's disease dementia at enrollment. Approximately 69% of participants carried the ApoE4 genetic risk variant, including 23% who carried two copies of the gene.

Biogen stated that additional analyses from the CELIA study, along with further findings from the ongoing long-term extension study, will be presented at future scientific and medical conferences as the company prepares to advance diranersen into Phase 3 clinical testing.