Donanemab (LY3002813) is an investigational immunotherapy for Alzheimer’s disease being developed by Eli Lilly. It is an antibody designed to stimulate the patient’s immune system to attack and destroy proteins in the brain that are believed to cause the neurodegeneration seen in Alzheimer’s.

How Donanemab works

The symptoms of Alzheimer’s disease are caused by the loss of connections between, and death of, brain cells. What causes these cells to die is not fully understood, but researchers think it may be the accumulation of certain proteins in the brain. One of these proteins is beta-amyloid. It can form clumps called “plaques” which may trigger inflammation, disrupt brain cell communication, and lead to cell death.

Donanemab is a type of antibody. Antibodies are a type of protein, made by the immune system that bind to an antigen, a foreign substance or disease-causing agent in the body. Sometimes antibodies can neutralize the antigen simply by binding to it. In other cases, this binding attracts other immune system cells that destroy the antigen.

Researchers designed donanemab to bind to a form of beta-amyloid protein that already has aggregated into plaques. A study using mice showed that donanemab stimulated the immune system to attack beta-amyloid plaques and clear them from the brain. It appeared donanemab was able to clear plaques without causing microhemorrhages, or small bleeding areas, in the brain.

Donanemab in clinical trials

A small Phase 1 clinical trial (NCT01837641) examined the safety, tolerability, and pharmacodynamics (how the body absorbs and processes the treatment) of donanemab in 100 patients with mild Alzheimer’s and healthy volunteers. The study was completed in 2016, but the results have not been published.

A larger Phase 1 clinical trial of donanemab (NCT02624778) recruited 61 participants with mild-to-moderate Alzheimer’s disease who were 50 or older. Participants received either a placebo, a single, or multiple intravenous doses of donanemab. Blood samples were taken from participants to monitor their levels of donanemab, as well as their immune system’s response to it. Participants also underwent PET scans to allow researchers to visualize and monitor beta-amyloid plaques in their brains. The study monitored participants for up to 72 weeks. No results have been posted yet.

There also is a Phase 2 clinical trial (NCT03367403, TRAILBLAZER-ALZ) of donanemab that has recruited 266 participants with early-stage Alzheimer’s disease in the U.S. and Canada. The trial continues but is no longer recruiting participants. This trial is evaluating the safety, tolerability, and effectiveness of donanemab, alone and in combination with LY3202626, to inhibit the production of beta-amyloid. Some participants will receive a placebo. Participants are between  60 and 85 years old with mild Alzheimer’s. Over the 18-month duration of the study, their cognitive function will be monitored using a variety of assessments and researchers will use PET and MRI scans to monitor beta-amyloid plaques and brain health. In October 2018, Lilly decided to continue the trial but without the addition of LY3202626 due to poor results of the drug in other trials. The study is estimated to be completed in November of 2021.

 

Last updated: Sept. 24, 2019

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