Biogen presented detailed data on July 14 from a mid-stage trial of its tau-targeting antisense oligonucleotide for Alzheimer’s disease at the Alzheimer’s Association International Conference in London. The company reported that the therapy, diranersen, slowed clinical decline in patients with mild cognitive impairment due to Alzheimer’s or mild Alzheimer’s over an 18-month period.
Szofia Bullain, vice president of Alzheimer’s disease and dementia clinical development at Biogen, said before the presentation, “As a clinician, I am excited to see that we now can target successfully another core pathology of Alzheimer’s disease.”
The Phase 2 CELIA trial enrolled 416 patients and tested several doses of diranersen. According to Biogen's press release, a 60-mg dose led to a 26% slowing on the Clinical Dementia Rating Sum of Boxes (CDR-SB) after 18 months and also slowed cognitive decline on other scales. Although diranersen missed its primary endpoint—statistically significant dose response for change from baseline on CDR-SB—Biogen stated that “CDR-SB results favored diranersen versus placebo across all studied doses.” The company noted that higher doses were not associated with greater slowing of decline.
Holly Kordasiewicz, Ionis Head of Development, said the CELIA study was designed as a dose-finding study for Phase 3 and “to show some of that initial proof of efficacy, so you can have some confidence going into that Phase 3 study.” She added, “The study hit all those objectives that it needed to hit on, even though it didn’t hit on that primary endpoint.”
At AAIC, Biogen also announced that diranersen is the first tau-directed therapy to demonstrate robust reductions in both cerebrospinal fluid total tau (50–65%) and brain tau pathology as measured by PET scans across all studied doses. Bullain described these reductions as “unprecedented.” Laura Nisenbaum from the Alzheimer’s Drug Discovery Foundation called this “the first signal that we might be able to move beyond amyloid.”
Biogen confirmed plans to proceed with a Phase 3 trial regardless of missing the primary endpoint. Bullain said future studies will seek consistency in results at larger scale: “We would again look for robust target engagement...and the same clinical benefits. If we could replicate those numbers...we certainly would be very happy.”
