The company reported 18-month cognitive and biomarker improvements in early Alzheimer’s disease, though the CELIA study missed its primary endpoint on dose response at Week 76.
Biogen said it plans to advance diranersen into confirmatory Phase 3 development after Phase 2 CELIA data showed 18-month clinical effects and reductions in tau biomarkers in early Alzheimer’s disease. In the study, diranersen 60 mg given intrathecally (into the spinal canal) every six months showed the strongest response versus placebo, with slowing of clinical decline by 0.54 points, or 26%, on CDR-SB, alongside 42% on ADAS-Cog13, 50% on MMSE, 30% on modified iADRS, and 23% on ADCOMS. The company also said diranersen became the first tau-directed therapy in a Phase 2 study to show reductions in both CSF (cerebrospinal fluid) total tau and brain tau pathology measured by PET (imaging scan). CELIA did not meet its primary endpoint because higher doses did not produce greater benefit on CDR-SB at 18 months, but results on that measure favored diranersen over placebo across all studied doses. Biogen said the investigational antisense oligonucleotide, which targets MAPT mRNA (genetic instructions for tau) to reduce production of all tau isoforms, was generally well tolerated and is not expected to cause ARIA (amyloid-related imaging abnormalities), a side effect associated with some amyloid-focused therapies.