ADDF Statement on FDA Committee Endorsing Donanemab

The FDA Peripheral and Central Nervous System Drugs Advisory Committee has voted unanimously to acknowledge donanemab's clinical benefits for early Alzheimer's disease treatment, marking a significant milestone for Alzheimer's treatment. If the drug receives full approval, it will be the second disease-modifying drug for Alzheimer's, expanding the treatment options for combination therapy.

Dr. Howard Fillit, Co-Founder and Chief Science Officer of the Alzheimer's Drug Discovery Foundation (ADDF), emphasizes the importance of looking at this development within the broader context of Alzheimer's treatment. He notes that a combination therapy and precision medicine approach will be essential for future treatments. Donanemab, if approved, will join the first class of disease-modifying drugs, providing foundational elements for future treatments. Although anti-amyloids are not a complete solution, they offer patients a way to modify the disease's progression while researchers work on developing therapies targeting the underlying biology.

The donanemab trials, particularly the TRAILBLAZER-ALZ 2 trial, showcase the field's ability to conduct innovative biomarker-powered trials. These trials used amyloid and tau imaging to identify patients in the early stages of Alzheimer's who would most likely benefit from treatment. Dr. Fillit highlights that some patients achieved full amyloid clearance with donanemab, with no significant plaque buildup resurgence for nearly four years. This success is attributed to biomarker tests that detect, quantify, and monitor plaque buildup in the brain. These biomarkers are expected to revolutionize clinical trial design as researchers develop drugs targeting novel pathways guided by the biology of aging.

The milestone comes at a time when drug development is increasingly driven by the biology of aging approach. Currently, nearly 75% of Alzheimer's drugs in development are targeting novel aspects related to aging pathways, such as inflammation, metabolic disturbances, and vascular dysfunctions. Promising drugs are being developed by companies funded by ADDF, including Coya Therapeutics, which is working on a combination therapy targeting neuroinflammation, and Therini Bio, which is developing a drug to target vascular dysfunction. PharmatrophiX has also completed a phase 2a trial for a neuroprotective drug, now ready for phase 2b trials.

The diversity in the drug pipeline, along with advances in biomarkers—particularly accessible and scalable blood-based biomarkers—sets the stage for a new era in Alzheimer's care. This era emphasizes early detection, diagnosis, and intervention. Biomarkers will also play a crucial role in disease prevention by identifying patients in the preclinical phase before symptoms appear and reducing Alzheimer's risk based on individual biomarker profiles.

Dr. Fillit concludes that the advisory committee's endorsement is a significant achievement for researchers, patients, families, and caregivers. However, the work to advance new treatment options must continue. The goal is to move towards a future where Alzheimer's is treated on an individual basis with precision medicine, ultimately halting or preventing the disease's progression.

The Alzheimer's Drug Discovery Foundation (ADDF), founded in 1998 by Leonard A. and Ronald S. Lauder, is committed to accelerating the discovery of drugs to prevent, treat, and cure Alzheimer's disease. The ADDF employs a venture philanthropy model to support research in academia and the biotech industry. Their leadership has significantly contributed to bringing the first Alzheimer's PET scan (Amyvid®) and blood test (PrecivityAD®) to market. Through the generosity of its donors, the ADDF has awarded more than $290 million to over 750 Alzheimer's drug discovery programs, biomarker programs, and clinical trials in 20 countries.