On May 3^rd, 2023 Ely Lily  announced positive results from their phase 3 clinical trial (TRAILBLAZER-ALZ2) for the drug, Donanemab, a monoclonal antibody (Lilly’s Donanemab Significantly Slowed Cognitive and Functional Decline in Phase 3 Study of Early Alzheimer’s Disease, n.d.). This is the third Amyloid plaque clearing drug after Biogen’s Aducanumab and Eisai’s Lecanemab in two years! Alzheimer’s Disease (AD) is characterized by accumulation of Amyloid plaques and neuronal Tau (protein) deposits. Donanemab was developed to reduce the Amyloid plaques in the brain. The drug significantly reduced cognitive loss by 35% in some individuals in a clinical trial of 1736 participants. In addition, Amyloid plaques were cleared from the brain of participants as assessed by positron emission tomography (PET) scans. However, 31.4% of the participants given the drug showed typical side effects of brain swelling and bleeding including 2 deaths. The details of the study are still to be published.

Late last year results from TRAILBLAZER-ALZ, a Phase 2 trial were published (Shcherbinin et al., 2022). For the phase 2, the company recruited 272 participants with early signs of Alzheimer’s Disease with mild cognitive impairment. Participants were randomly split to two groups; one received a placebo, and the other group was given the drug. Primary endpoint of the trial was reduction in Amyloid plaques and Tau deposits. Representative figure (below) shows dramatic reduction in Amyloid plaques some participants. In fact, 68% of those who received the drug showed clearance of amyloid plaques by 76 weeks.

Figure1: Reproduced from supplementary figure (Shcherbinin et al., 2022); CL refers to centiloids, a unit used to quantify the levels of Amyloid plaque. In these images, the red/orange/yellow tones represent a higher level of Amyloid plaque whereas the blue/green tones represent lower levels. Donanemab reduced the Amyloid plaques dramatically!