ADDF Statement on New Results from Donanemab’s TRAILBLAZER-ALZ 2 Trial

Data show that the anti-amyloid is modestly effective in reducing cognitive decline, underscoring the need to develop additional drugs that target other pathways guided by the biology of aging

July 17, 2023 —The Alzheimer’s Drug Discovery Foundation (ADDF) is encouraged to see the positive data reported by Eli Lilly and Company today for its anti-amyloid drug, donanemab, which was unveiled at the Alzheimer’s Association International Conference (AAIC) in Amsterdam and published in JAMA. The data serve as another proof point that anti-amyloid therapies are just the first class of disease modifying therapies, further validating the ADDF’s cornerstone belief that Alzheimer’s will need to be treated with combination therapy, like other complex diseases of aging.

“Today’s results are promising, with donanemab slowing cognitive decline by 35% in patients with early-stage Alzheimer’s disease, making it all the more apparent that anti-amyloid therapies will serve as the first line of defense in the arsenal of drugs needed to treat this disease,” says Howard Fillit, MD, Co-Founder and Chief Science Officer of the ADDF. “But this is just a start, and we must continue advancing the drug pipeline to develop the next class of drugs centered around the biology of aging to ultimately stop Alzheimer’s in its tracks. Like in cancer, the goal is to address the many underlying pathologies of the disease through a precision medicine approach.”

With the advent of multiple anti-amyloid therapies, the stage is now set for the next generation of clinical trials, where amyloid-targeting drugs will be combined with other novel drugs to provide additional clinical benefit for patients. Based on the biology of aging, there are multiple pathways involved in the onset of Alzheimer’s, with the accumulation of misfolded proteins serving as one target in addition to inflammation, metabolic disturbances, vascular dysfunction and more. The robust drug pipeline—where 75% of drugs in clinical development are focused on novel pathways—is primed for this next phase of clinical trials.

“Advancements in clinical trial design have been a driving force behind the recent Alzheimer’s breakthroughs, and there’s still more progress to come,” notes Dr. Fillit. “In the next wave of trial design, researchers must begin conducting combination therapy clinical trials that use precision biomarkers to gain a deeper understanding of how multiple drugs interact with one another as part of a broader treatment strategy for Alzheimer’s.”

Studies like the phase III TRAILBLAZER-ALZ 2 study demonstrate the value in conducting biomarker-powered clinical trials. Lilly’s highly effective trial design used two biomarkers, including the Amyvid® PET scan—which was developed with early seed funding from the ADDF—and the TAUVID™ PET scan, to enroll patients and measure target engagement of the drug.

Leqembi’s recent FDA approval, alongside the recent donanemab data, is a watershed moment, proving that forty years of research has provided

“Today marks an important step in our journey to develop new and effective Alzheimer’s therapies, but our job is not done yet,” adds Dr. Fillit. “Recent success in anti-amyloid research spurs optimism and will serve as a catalyst for new investments in the pipeline and a stronger focus on the biology of aging. The results of the TRAILBLAZER-ALZ 2 trial accelerate recent momentum, bringing us one step closer to making Alzheimer’s a treatable, and eventually, a preventable disease.”

Lilly has submitted donanemab to the FDA for traditional approval and a decision is expected to be announced by the end of the year.