Key Takeaways:
Biogen's diranersen slowed cognitive decline by 26% on the Clinical Dementia Rating Sum of Boxes and reduced tau protein by 50-65% in a phase 2 trial, providing the first proof that targeting tau can alter Alzheimer's disease progression.
"The CELIA data provide some of the clearest evidence that reducing tau pathology can translate into clinically meaningful benefit," Cath Mummery, professor of clinical neurology at UCL Queen Square Institute of Neurology, said.
The 60 mg dose, injected into the spine every six months, showed the strongest response across five of six assessment tools, including a 42% slowing on ADAS-Cog13 and 50% on the Mini Mental State Examination. Higher doses of 115 mg produced smaller benefits, causing the study to miss its primary endpoint of dose-dependent response. No separation from placebo was observed on the ADCS-ADL-MCI daily functioning measure, a result Biogen's head of Alzheimer's clinical development Szofia Bullain called "puzzling."
The results position Biogen to compete in the $30 billion-plus Alzheimer's market alongside its own anti-amyloid drug Leqembi and Eli Lilly's Kisunla, but without the brain-swelling side effect known as ARIA. Biogen plans to start a pivotal phase 3 trial in 2027 with data expected by 2030-2031.
How Diranersen Differs From Anti-Amyloid Antibodies
Diranersen is an antisense oligonucleotide that targets MAPT mRNA to block production of all tau protein isoforms, both inside and outside neurons. This mechanism differs from antibody approaches that only capture tau as it moves between cells. By stopping new tau production, the brain's natural clearance systems can remove existing tangles, Holly Kordasiewicz, senior vice president of neurology research at Ionis Pharmaceuticals, said. Ionis discovered the drug; Biogen licensed it in 2019.
The approach also avoids ARIA, the brain swelling and bleeding complication that affects 12-17% of patients on Leqembi and Kisunla. More than 90% of CELIA participants who completed the placebo-controlled period elected to continue into the extension study, signaling tolerability.
Competitive Landscape Heats Up
The CELIA results could affect companies developing other gene-silencing tau drugs. Voyager Therapeutics is advancing a small interfering RNA targeting MAPT, with plans to enter the clinic later this year. Denali Therapeutics is pursuing both tau and amyloid programs using blood-brain barrier-crossing molecules. Arrowhead Pharmaceuticals also has a tau-targeting candidate in development.
JPMorgan analyst Chris Schott had been looking for at least 30% slowing on CDR-SB, while Baird analyst Jack Allen said a 0.4-point difference was the threshold for a meaningful therapeutic effect. The 0.54-point benefit at 60 mg exceeded that bar. Lawren VandeVrede, a neurologist at the University of California, San Francisco and CELIA investigator, said the efficacy was "probably comparable to the existing drugs in some cases, maybe a little bit better on some metrics."
Biogen has not committed to a specific phase 3 dose, though Bullain said the 60 mg regimen "definitely distinguishes itself." The company is consulting with Alzheimer's experts and health authorities as it designs the confirmatory trial.
This article is for informational purposes only and does not constitute investment advice.
