Biogen said Thursday it will push its experimental Alzheimer’s drug, diranersen, into a late-stage registrational trial after a middling-but-promising midstage readout that showed reductions in tau and signs of slower cognitive decline. The drug is an antisense oligonucleotide given into the spinal canal and designed to lower toxic tau inside neurons, a mechanism researchers have been eager to see properly tested in patients. Even though the Phase 2 CELIA study missed its predefined dose response primary endpoint, Biogen said the total mix of biomarker and clinical signals was strong enough to justify moving the program ahead.
What the CELIA trial found
In a press release, Biogen said CELIA was an 18 month, randomized, placebo controlled Phase 2 study that enrolled 416 people with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s dementia and tested three intrathecal dosing regimens. The company reported that the trial did not meet its primary endpoint, a dose response change on the Clinical Dementia Rating Sum of Boxes at week 76, but it saw robust reductions in cerebrospinal fluid tau and in tau PET and reported prespecified analyses showing slowing of clinical decline across doses, particularly at the lowest dose. Biogen said full data will be presented at the Alzheimer’s Association International Conference and that it plans to engage regulators on how best to run a registrational program.
How researchers reacted
Priya Singhal, Biogen’s head of development, called the topline “an unprecedented and compelling combination of tau reduction and an impact on cognitive benefit” in an interview with The Boston Globe. Analysts welcomed the biomarker signal but urged caution, noting that more detail on safety and the unusual dose response pattern will be needed before clinicians and investors fully embrace a registrational push.
Where this fits in Alzheimer’s research
Approved disease modifying treatments so far, including Leqembi as described by the FDA and Kisunla as detailed by Drugs.com, target amyloid, not tau, and researchers have long debated which protein should be the main focus as therapies advance. The Alzheimer’s Association called the CELIA topline an important advance because tau is closely linked to symptoms, while outlets including STAT have pointed to recent tau setbacks such as Johnson & Johnson’s decision to halt its posdinemab midstage study in late 2025. Those failures are a reminder of why regulators and scientists will go over the full CELIA dataset in detail once it is released.
What’s next
Biogen said it will consult with experts and regulators about the design of a pivotal program and will present the complete CELIA dataset at AAIC later this year; the company also noted that diranersen received FDA Fast Track designation in 2025. Regulators and independent experts are expected to press for clarity on dose selection and safety monitoring, given the intrathecal route and the uneven dose response signal.
Ionis, which discovered diranersen and licensed it to Biogen, called the toplines “highly encouraging” in its own statement and said it looks forward to presentations of the full data. The companies added that long term extension data are continuing to mature as work on the program continues. Ionis provided its press release on the readout.
