Biogen (NASDAQ:BIIB) said data from its Phase 2 CELIA study of diranersen in early Alzheimer’s disease provide proof of concept for the tau-targeting therapy, despite the trial not meeting its primary endpoint of demonstrating a predefined dose-response pattern.
The company presented the update during a webcast from the Alzheimer’s Association International Conference, where executives said the results support advancing diranersen into Phase 3 development. Priya Singhal, Biogen’s executive vice president and head of development, said the company believes the data show “an important advancement in targeting tau,” citing reductions in tau pathology and signals across clinical endpoints.
CELIA Did Not Meet Dose-Response Primary Endpoint
Diana Gallagher, Biogen’s head of Alzheimer’s and dementia and MS and immunology development units, said CELIA enrolled patients with early Alzheimer’s disease and mild cognitive impairment over an 18-month period. Participants were randomized to placebo or one of three diranersen dose levels. The study measured clinical endpoints including CDR Sum of Boxes, ADAS-Cog 13, MMSE, ADCS-ADL-MCI, modified iADRS and ADCOMS.
The primary endpoint was designed to assess whether increasing doses improved efficacy on CDR-SB compared with a predefined dose-response rate. Gallagher said the trial did not show that dose-response pattern.
However, Biogen said diranersen was favored over placebo across nearly every endpoint. Executives repeatedly pointed to the 60 mg dose administered every six months as the dose that showed the “largest and most substantial” benefit across most measures.
Singhal said the company believes the 60 mg twice-yearly dose is emerging as the dose to take forward, supported by clinical and biomarker findings. She also said the CDR-SB benefit at 18 months was similar to anti-amyloid therapies, while cognitive signals were stronger than what Biogen has seen historically in Alzheimer’s trials of potential disease-modifying therapies.
Biogen Highlights Tau PET Reductions
Gallagher said diranersen differs from antibody approaches by targeting the reduction of MAPT gene translation into tau protein, reducing production of all isoforms of tau inside the cell. She said Biogen’s hypothesis is that lowering tau production can reduce tau pathology in the brain and potentially translate to clinical benefit.
In the CELIA study, Biogen measured total tau in cerebrospinal fluid for all subjects and tau PET in a substudy representing about 30% of patients. Gallagher said the placebo group showed the expected increase in tau burden in early Alzheimer’s disease, while all three diranersen arms showed reductions from baseline in tau pathology accumulation.
“This has never been seen before with any other tau-directed agents, and in our view, this is a very important finding,” Gallagher said.
Safety Profile and Confusional State Events
Biogen said diranersen was generally well tolerated in CELIA, with no new safety signals compared with the prior Phase 1b study. Most adverse events were mild or moderate and not serious, Gallagher said. She also noted that amyloid-related imaging abnormalities, or ARIA, were not observed, which Biogen said was consistent with expectations for diranersen’s mechanism of action.
Confusional state was reported as an adverse event, with higher incidence at higher doses. Gallagher said most events were mild to moderate, typically occurred within seven days of dosing and resolved within about another week. She said the timing was not consistent with tau lowering, which takes longer to occur.
Singhal said 94% of eligible patients who completed CELIA entered the ongoing long-term extension study, which she described as encouraging given the intrathecal administration route.
Phase 3 Planning Underway
Biogen said it is working on a Phase 3 study design and broader evidence-generation plan, while engaging with external experts and regulators. Singhal said the company expects two-year CELIA data by the close of 2026 and plans to share and publish additional data at medical congresses and in medical literature.
During the question-and-answer session, analysts pressed Biogen executives on the lack of dose response, baseline imbalances, functional endpoints and whether the therapy could eventually be used with anti-amyloid drugs such as LEQEMBI. Gallagher said Biogen is focused first on establishing diranersen as a tau monotherapy in Phase 3, while also considering future data generation around sequential or combination approaches.
Singhal said the company is not waiting for the long-term extension to finish before moving ahead with Phase 3 planning. She said an end-of-Phase 2 meeting with regulators is a priority.
“While, yes, we didn’t hit the dose response, we think that the data set is very encouraging with clear signals,” Singhal said. “We think that the data in totality really makes complete sense for us to forward this to Phase 3.”
About Biogen (NASDAQ:BIIB)
Biogen Inc is a multinational biotechnology company focused on discovering, developing and delivering therapies for neurological and neurodegenerative diseases. Headquartered in Cambridge, Massachusetts, the company has a longstanding emphasis on neuroscience, with research and commercial activities spanning multiple therapeutic areas including multiple sclerosis, spinal muscular atrophy and Alzheimer’s disease. Biogen was founded in 1978 and has grown into a global biopharmaceutical firm with operations and commercial presence across North America, Europe, Japan and other international markets.
The company’s marketed portfolio has historically included several well-known therapies for multiple sclerosis such as Avonex, Tysabri and Tecfidera, and it has pursued treatments for rare neurological conditions and genetic neuromuscular disorders.
