Biogen's anti-tau Alzheimer's drug shows mixed but encouraging results in mid-stage trial

Biogen (BIIB) said that the lowest dose of its experimental Alzheimer's drug diranersen reduced cognitive decline across five of six standard assessment tools and cut levels of a toxic brain protein by up to 65%, even as the treatment missed its primary goal in a mid-stage clinical trial.

The results, presented at the Alzheimer's Association International Conference in London, nonetheless represent a milestone for the field: the first evidence that lowering tau — a protein closely associated with brain cell death and cognitive decline — can alter the course of the disease. Unlike prior failed drugs that attempted to clear toxic forms of tau using antibodies, diranersen works by silencing the gene responsible for producing all forms of the protein.

"This trial, as far as I'm concerned, is proof of principle. If you change tau, you can change the course of the disease, and we haven't had that before," said Cath Mummery, professor of clinical neurology at University College London, who led the study.

The 18-month Phase 2 CELIA trial enrolled 416 patients with early Alzheimer's and tested three dose regimens of the drug, administered via spinal injection. As previously disclosed in May, the trial failed to demonstrate a dose-dependent response on the Clinical Dementia Rating-Sum of Boxes, or CDR-SB — a widely used 18-point assessment scale. In fact, the lowest 60 mg dose outperformed higher doses, a pattern researchers described as the inverse of what was anticipated.

At the 60 mg dose, diranersen slowed cognitive and functional decline by 26%, or 0.54 points, versus placebo on the CDR-SB. That performance is broadly comparable to the 25-30% slowing seen in Phase 3 trials of Leqembi, developed by Biogen and Eisai (ESALY), and Eli Lilly's (LLY) Kisunla — both of which target amyloid, a separate Alzheimer's-related protein.

The 60 mg dose also demonstrated meaningful benefit across several secondary measures: a 42% slowing of decline on the ADAS-Cog13 cognitive tracking scale; a 50% slowing on the MMSE cognitive function test; a 30% slowing on the modified iADRS measure of cognition and daily function; and a 23% slowing on ADCOMS, which is designed to detect early-stage decline. No statistically significant benefit was observed on the ADCS-ADL-MCI, a measure of daily functioning, though Biogen said it is continuing to follow patients on that scale for 24 months.

The 26% slowing on the primary endpoint fell short of the 30% or greater threshold JPMorgan analyst Chris Schott had flagged as a benchmark, though Baird analyst Jack Allen said a difference of 0.4 points or more on CDR-SB was sufficient to constitute a meaningful therapeutic effect.

Side effects were described as mild to moderate and largely procedural — including pain, headache, and transient confusion associated with the lumbar puncture delivery method. Notably, there were no cases of ARIA, the brain-swelling condition that has been observed with amyloid-targeting therapies such as Leqembi and Kisunla.

Maria Carrillo, chief science officer of the Alzheimer's Association, acknowledged the missed primary endpoint but called diranersen "worth pursuing," noting the consistency of benefit seen across secondary measures. Biogen's head of development, Dr. Priya Singhal, said the cumulative data provided sufficient grounds to advance the program, with a single pivotal Phase 3 trial planned to begin in 2027 and data expected between 2030 and 2031.

Analysts said the results could have broader implications for other companies developing gene-silencing approaches to tau, including Voyager Therapeutics (VYGR), Arrowhead Pharmaceuticals (ARWR), and Denali Therapeutics (DNLI).