Biogen presented data on July 15 from a mid-stage trial of its antisense therapy diranersen at the Alzheimer’s Association International Conference, showing a correlation between tau reduction and clinical benefit in patients with Alzheimer’s disease. Despite the findings appearing to validate the anti-tau hypothesis, Biogen’s stock fell over 8% during trading as analysts focused on unresolved questions about the robustness and replicability of the results.
RBC Capital Markets analysts said, “CELIA, You’re Breaking My Heart,” referencing the Phase 2 trial's name. They continued, “Today’s data are mostly in line with our expectations, with some supportive signals, but also still maintain questions around how robust and replicable the data set is.” Mizuho analysts noted that “the biggest disconnect ... is that tau reduction (the actual hypothesis for this program) didn’t always translate (in the higher dose arms) to obvious clinical benefit.” The lowest dose of diranersen showed a 26% slowing of decline versus placebo after 26 weeks; however, higher doses produced less positive outcomes. William Blair described an “inverse” dose response where increasing doses yielded smaller benefits.
Biogen acknowledged these unexpected results and confirmed that diranersen missed its Phase 2 endpoint but plans to proceed to Phase 3 trials. William Blair compared diranersen's efficacy unfavorably to approved anti-amyloid therapies such as Leqembi and Kisunla but suggested that CELIA study data looked better than UCB’s bepranemab TOGETHER dataset. Laura Nisenbaum, interim chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), said in a statement shared Tuesday, “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.”
The article provides context about other failed attempts at developing anti-tau therapies for Alzheimer's disease. In November 2024, UCB's bepranemab did not improve cognition or function in its Phase 2 trial; Johnson & Johnson's posdinemab also failed in its own study one year later. Diranersen differs by targeting mRNA of the MAPT gene using an antisense oligonucleotide approach designed to reduce both intracellular and extracellular forms of tau protein.
Other companies are pursuing similar approaches. Eisai is developing etalanetug with University College London; Denali Therapeutics has DNL628 using their Oligonucleotide TransportVehicle platform; Arrowhead Pharmaceuticals has initiated studies on ARO-MAPT; Eli Lilly is working on an siRNA molecule targeting tau.
Nisenbaum expressed cautious optimism about Biogen's recent results: “Tau is one of the two defining pathologies of Alzheimer’s disease and has long been difficult to target, which makes these results all the more notable,” she said. However, she added that discrepancies between biomarker changes and clinical endpoints raise important questions about optimal dosing strategies for future studies.
