FDA Advisory Committee Unanimously Agrees that Donanemab Holds Clinical Benefit for Early Alzheimer Disease

The Food and Drug Administration (FDA) Peripheral and Central Nervous System Drugs Advisory Committee has voted in unanimous agreement that donanemab (Eli Lilly and Company, Indianapolis, IN) has demonstrated clinical benefit in the treatment of early Alzheimer disease (AD). The vote follows the publication of results from the phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511) and a subsequent post-hoc analysis, showing that people with early AD treated with donanemab showed slower reductions in measures of cognitive and functional decline.

According to a statement from the Alzheimer’s Drug Discovery Foundation (ADDF), donanemab has the potential to become the second disease-modifying drug to receive full approval from the FDA for the treatment of people with AD, following the approval of Leqembi (lecanemab-irmb; Eisai, Tokyo, Japan; Biogen, Cambridge, MA) in 2023. The TRAILBLAZER-ALZ 2 study was also significant for its use of amyloid and tau PET imaging and plasma phosphorylated tau at threonine 217 (p-tau217) biomarker testing to identify participants most likely to benefit from treatment. In their statement, the ADDF suggests that biomarker testing and novel therapeutic targets hold promise for advancing detection, diagnosis, and intervention for AD.

“It's encouraging to see that some patients essentially enter remission, where they achieve full amyloid clearance with donanemab, with no resurgence in substantial plaque buildup for nearly four years,” said Howard Fillit, MD, Co-Founder and Chief Scientific Officer of the ADDF. "These findings are a direct result of biomarker tests that can detect, quantify, and monitor plaque buildup in the brain. Biomarkers will continue to revolutionize clinical trial design as we move towards developing drugs that target novel pathways guided by the biology of aging."