ADDF Statement on Topline Results from Phase 3 Trial of Amyloid-Clearing Drug Donanemab

Amyloid-targeting drugs make up one part of the biology of aging approach and are the first step in developing multiple drugs to treat Alzheimer’s disease

The Alzheimer’s Drug Discovery Foundation (ADDF) is encouraged to see the positive data reported today by Eli Lilly and Company for their amyloid-clearing antibody donanemab. Topline results from the TRAILBLAZER-ALZ 2 phase 3 study show the drug slowed cognitive and functional decline by 35% in patients with early symptomatic Alzheimer's disease and reduced amyloid plaque levels in the brains of treated patients.

"This is very encouraging news for the millions of patients and families suffering from Alzheimer’s disease," said Dr. Howard Fillit, Co-Founder and Chief Science Officer of the ADDF. "These data are another proof point that amyloid-targeting drugs are a first step to slowing cognitive and functional decline, providing a clinically meaningful benefit to patients."

Over half of participants in the trial completed their course of treatment by 12 months, which indicates a possibility that the drug could be paused or stopped after a year, potentially lowering cost and limiting risk of side effects for patients. The trial reported three deaths related to side effects from treatment. Dr. Fillit advises patients and their caregivers to discuss the risk and benefit with their physician and stresses the importance of risk management and usage guidelines for anti-amyloid monoclonal antibodies.

"Based on our understanding of the biology of aging, we know the accumulation of misfolded proteins is one pathway, among others, that contributes to the onset of Alzheimer's," said Dr. Fillit. "Our job now is to develop the next generation of drugs that can target all these pathways and be used in combination with one another for a precision medicine approach enabled by new biomarkers. While the results from this trial are highly significant, further progress is needed to achieve 100% slowing of cognitive decline."

Anti-amyloid therapies can serve as the first disease-modifying drugs in the arsenal of treatments we will need to effectively treat Alzheimer’s. The development of the next generation of drugs is already well underway with 75% of trials currently in the pipeline aimed at novel targets beyond the traditional amyloid and tau.

As these trials for novel targets advance, it further underscores the importance of developing complimentary biomarkers. Biomarkers like the Amyvid® PET scan – which received early seed funding from the ADDF – and the Tauvid™ PET scan are already being used to enroll patients in trials for amyloid-targeting drugs, like donanemab, and to demonstrate target engagement.

"The path to new Alzheimer’s therapies starts with an early and accurate diagnosis. Biomarkers are essential if we hope to use drugs most effectively for the patients who need them," said Dr. Fillit. "They will play a key role, allowing us to match the right drugs to the right patients at the right time. We need to know what each patient’s disease looks like to give us the best chance of treating it."

Lilly plans to release the full results of their phase 3 trial at the Alzheimer's Association International Conference (AAIC) in July and intends to submit the drug for approval from the FDA by the end of the second quarter.