New Alzheimer’s Drug Dramatically Slows Disease Progression

A new drug called donanemab could help slow the onset of severe Alzheimer’s symptoms. Eli Lilly, an international pharmaceutical company, announced Monday that its Phase 3 donanemab trials “significantly slowed cognitive and functional decline” in participants with early Alzheimer’s. The drug will now move through the US Food and Drug Administration’s (FDA) regulatory pipeline, hopefully receiving a decision by the end of the year.

Alzheimer’s is believed to be caused by amyloid, a protein aggregate that builds up between neurons. The resulting plaques make it difficult for neurons to function, leading to what we perceive as memory loss, poor judgment, and other cognitive concerns. While the “amyloid theory” has faced its obstacles over the years, it’s still the prevailing theory as to how Alzheimer’s occurs, thereby influencing drug development and other forms of treatment. 

Donanemab is an antibody that targets amyloid plaques. By binding with the plaques directly, donanemab neutralizes them and begins to clear them away. Clearing the plaques might not restore what cognitive strengths have already been lost, but research suggests it does prevent Alzheimer’s from progressing as quickly as it otherwise would. 

Credit: Robina Weermeijer/Unsplash

Eli Lilly’s trial involved 1,736 participants with varying Alzheimer’s symptom severities as measured by the Alzheimer’s Disease Rating Scale (iADRS) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB). All participants were proven amyloid-positive prior to beginning donanemab treatment, which involved regular intravenous injections. Although a placebo group only experienced a 1% reduction in amyloid plaque, the donanemab saw a whopping 84% reduction within 18 months of treatment. In participants with mild Alzheimer’s symptoms, donanemab slowed cognitive decline by 35% as measured by the iADRS and 36% as measured by the CDR-SB. While Eli Lilly didn’t publicly specify the rate at which progression slowed for participants with more severe symptoms, it did say that the entire donanemab group experienced an average 22% slowdown as measured by the iADRS and 29% as measured by the CDR-SB. 

As far as the downsides go, donanemab appeared to have caused swelling and bleeding of the brain in a small fraction of participants. (No drug is without its side effects, but these are quite serious.) Also, based on this trial alone, donanemab appears slightly less effective in participants with higher age groups. Those under 75 experienced a 48% and 45% slowdown on the iADRS and CDR-SB, respectively, while those aged 75 and over saw a slowdown of 25% and 29%. Nonetheless, Eli Lilly has applied for FDA approval and hopes to receive a response by the end of 2023.