donanemab

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donanemab

GtoPdb Ligand ID: 8357

Comment: Donanemab (LY3002813) is a monoclonal antibody developed from the murine monoclonal mE8-IgG2a [1]. It binds to N-terminally, pyroglutamate-modified amyloid β proteins (abbreviated as Aβ_p3-x or N3pG) which are found extensively in the amyloid plaques of the brains of Alzheimer's disease (AD) patients. The removal of Aβ_p3-x is being investigated as a novel mechanism to treat AD.

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Summary of Clinical Use
Donanemab (LY3002813) was advanced to clinical evaluation in AD patients. In January 2021, the antibody developer, Eli Lilly issued a press release that announced that interim phase 2 data showed that donanemab promotes clearance of N3pG amyloid plaques from the brain, and that this is associated with a slowing of decline in cognition and daily function measurements in patients with early symptomatic AD. Eli Lilly state that the reduction in decline is statistically significantly different from the placebo group. This data has not yet been published.

Summary of Clinical Use

Donanemab (LY3002813) was advanced to clinical evaluation in AD patients. In January 2021, the antibody developer, Eli Lilly issued a press release that announced that interim phase 2 data showed that donanemab promotes clearance of N3pG amyloid plaques from the brain, and that this is associated with a slowing of decline in cognition and daily function measurements in patients with early symptomatic AD. Eli Lilly state that the reduction in decline is statistically significantly different from the placebo group. This data has not yet been published.

Mechanism Of Action and Pharmacodynamic Effects
Results with previous immunotherapies which target various soluble or insoluble Aβ proteins have largely been unsuccessful as they fail to clear existing Aβ. LY3002813 has been designed to target deposited plaque, as clearance of the existing amyloid burden is believed to be essential for any AD therapy to be effective. The mE8 antibody upon which LY3002813 was based, is reported to clear plaques in mice without causing microhemorrhages (a serious adverse event reported with previously trialled anti-Aβ monoclonals) [1].

Mechanism Of Action and Pharmacodynamic Effects

Results with previous immunotherapies which target various soluble or insoluble Aβ proteins have largely been unsuccessful as they fail to clear existing Aβ. LY3002813 has been designed to target deposited plaque, as clearance of the existing amyloid burden is believed to be essential for any AD therapy to be effective. The mE8 antibody upon which LY3002813 was based, is reported to clear plaques in mice without causing microhemorrhages (a serious adverse event reported with previously trialled anti-Aβ monoclonals) [1].

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT04437511	A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)	Phase 2 Interventional	Eli Lilly and Company
NCT03367403	A Study of LY3002813 in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ)	Phase 2 Interventional	Eli Lilly and Company