• In the Phase 1b study, favorable trends were reported for the high-dose groups on multiple measures of cognition and function.
• First study of a tau targeting drug that shows reduction of aggregated tau pathology and favorable trends on clinical outcomes.
• Recruitment is underway for the Phase 2 CELIA study further investigating clinical efficacy and safety.

In AD, both tau and amyloid beta are linked to disease progression.¹ Tau protein can form tangles which progressively accumulate in brain regions involved in cognition.² The accumulation of pathological tau tangles has been shown to lead to neuronal loss. ASO therapies are seen as promising tools for modulating production of disease-associated proteins. Currently, the ASO approach underpins more than 60 treatments approved or in clinical trials for a variety of disease areas including a range of cancers, viral illnesses, and genetic conditions.³

“This is the first time we’ve seen both strong target engagement and favorable trends on clinical outcomes with a novel mechanism targeting tau,” said Priya Singhal, M.D., M.P.H., Head of Development at Biogen. “While these are preliminary findings, we are excited about these results and continue to enroll the Phase 2 CELIA study. We believe defeating Alzheimer’s disease will take different approaches and we are committed to exploring the targeting of tau as a new generation of treatment.”

In results presented at CTAD, favorable trends were observed on the global Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini-Mental State Exam (MMSE) cognitive scales and Functional Activities Questionnaire (FAQ) at week 100 in groups treated with a high-dose of BIIB080 (n=16). The results build on data presented at the International Conference on Alzheimer’s and Parkinson’s Disease (ADPD^TM 2023) which showed that direct targeting of tau protein production had a substantial impact on tau biomarkers, reducing total and phosphorylated tau in the CSF and aggregated tau pathology as measured by PET across all brain regions assessed. The favorable trends suggest a potential link between a reduction in tau PET pathology and clinical outcomes.

Treatment was generally well tolerated throughout the study. The majority of adverse events were mild or moderate in severity, of which the most common were headache, back pain, pain in extremity, post-lumbar puncture syndrome and procedural pain.

BIIB080 is designed to target microtubule-associated protein tau (MAPT) mRNA and reduce production of tau protein. The Phase 1b trial and its long-term extension study (LTE) were designed to assess the safety and tolerability of multiple doses in patients with mild dementia due to AD. Participants were randomized to placebo or to four dose cohorts receiving 10mg once every 4 weeks [Q4W], 30mg Q4W, 60mg Q4W or 115mg Q12W. In the LTE, all participants received 60mg or 115mg every 12 weeks.

Recruitment for the Phase 2 CELIA study (NCT05399888), evaluating the potential for this ASO targeting tau to slow the worsening of mild cognitive impairment or mild dementia due to AD, is ongoing at sites across North America, Europe and Asia Pacific.

In December 2019, Biogen exercised a license option with Ionis and obtained a worldwide, exclusive, royalty-bearing license to develop and commercialize BIIB080.