Biogen Details Phase 2 CELIA Data for Anti-Tau Drug Diranersen, Plans Phase 3

Biogen presented full Phase 2 results for diranersen, its investigational tau-lowering antisense drug, at the Alzheimer's Association International Conference (AAIC) in London on July 14, and said it will take the drug into confirmatory Phase 3 development, NeurologyLive reported. The results are company-reported conference data.

The CELIA trial was designed to test whether higher doses gave greater benefit on the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale. They did not, and the primary dose-response endpoint was missed (p = 0.21), a result Biogen first disclosed in May without detailed data. Instead, the lowest dose produced the largest effects.

The results

Compared with placebo, the 60 mg dose given every 24 weeks slowed clinical decline at 18 months by 0.54 points, or 26%, on CDR-SB, by 42% on the ADAS-Cog13 cognitive scale and by 50% on the MMSE, according to NeurologyLive's account of the data. Most of those differences reached nominal statistical significance. The 115 mg doses given every 24 weeks and every 12 weeks slowed decline on CDR-SB by 14% and 9%. No dose separated from placebo on ADCS-ADL-MCI, a measure of daily functioning.

All doses cut total tau in cerebrospinal fluid by a mean of 50% to 65% from baseline by week 72, and a tau PET imaging substudy of 131 patients showed decreases across all brain regions evaluated, the report said. Serious adverse events were most frequent in the 115 mg every-12-weeks group, at 23.3%, and no amyloid-related imaging abnormalities were observed. The most frequent adverse events were procedural pain, post-lumbar puncture syndrome and confusional state.

CELIA enrolled 416 adults aged 50 to 80 with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's dementia, who received the drug by intrathecal injection over an 18-month placebo-controlled period, Alzheimer Europe reported. Diranersen targets the mRNA of the MAPT gene to suppress production of tau. It was discovered by Ionis Pharmaceuticals and licensed to Biogen in 2019, and the FDA granted it fast track designation in 2025.

Investor reaction

Biogen shares fell 8.17% on July 14, from a close of $209.03 the previous day to $191.95, Clinical Trials Arena reported.

Analysts focused on the inverse dose response and on how the 26% figure compares with approved anti-amyloid drugs, BioSpace reported. William Blair analysts wrote that, with cross-trial caveats, it sits at the lower end of the 27% to 29% slowing seen on CDR-SB in placebo-controlled studies of Leqembi and Kisunla.

"These are the first data from a randomized trial to show a tau-targeting drug producing both a robust biomarker effect and a signal of clinical benefit," Laura Nisenbaum, interim chief science officer at the Alzheimer's Drug Discovery Foundation, said in a statement to BioSpace.

Biogen said additional analyses and data from CELIA's long-term extension will be presented at future conferences.