Alzheimer’s Drug Discovery Foundation Comment on TRAILBLAZER-ALZ Results

Eli Lilly and Co announced clinical trial results for its experimental Alzheimer’s drug donanemab, which slowed decline in a combined measure of cognition and daily function in patients with early-stage Alzheimer’s disease. Donanemab is an investigational monoclonal antibody that targets a modified form of beta amyloid called N3pG.

“Donanemab slowed cognitive decline by 32% compared to placebo in this phase 2 trial, which, if confirmed in additional studies, would be a clinically meaningful finding for patients and their families,” said Howard Fillit, M.D., Founding Executive Director and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF). “I am encouraged by the progress we’re seeing in our research efforts through well-designed and rigorous trials like this.”

Following the model established in earlier trials, Lilly’s TRAILBLAZER-ALZ study used biomarkers to ensure appropriate patients were recruited. Investigators used Amyvid^TM PET scans to enroll patients with amyloid plaques in the brain and to track their progress. “One thing we know for sure is that there was target engagement, and the pharmacology of this drug works,” said Dr. Fillit, “because the amyloid plaques were cleared from patients’ brains. Another important part of this study is that, using Tauvid^TM PET scans, researchers also measured the tau tangles, which are more indicative of cognitive decline than the plaques.”

Like Biogen’s aducanumab study, Lilly’s study adds evidence to indicate that removing amyloid from the brain may slow cognitive decline in Alzheimer’s disease. Lilly has another phase 3 study ongoing to confirm the results.

However, Alzheimer’s is a complicated disease and a combination of drugs addressing multiple targets will be needed to effectively treat it. Many of the new treatments being investigated are focused on targets associated with the biology of aging.

The goal is to develop drugs that work on many different pathways, including those beyond amyloid, that are implicated in Alzheimer’s disease. There are more than 100 drugs currently in clinical trials that address novel targets including misfolded proteins, inflammation, vascular problems, genetic mutations, and age-related changes associated with Alzheimer’s.

“These latest findings, along with several other recent trial reports, and more anticipated this year, are the results of years of progress in basic science, drug discovery and development,” added Dr. Fillit. “This is a defining time as progress is moving us closer to more effective drugs for the prevention and treatment of Alzheimer’s disease and related dementias, bringing renewed hope to many patients and their families.”