The U.S. Food and Drug Administration (FDA) plans to convene a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee to further review Eli Lilly's investigational Alzheimer's treatment donanemab before making its final approval decision. The committee will examine the drug's efficacy and safety profile, with particular focus on data from the TRAILBLAZER-ALZ 2 clinical trial.
According to Howard Fillit, MD, Co-Founder and Chief Science Officer of the Alzheimer's Drug Discovery Foundation (ADDF), "Today's FDA decision is not a setback, but another step forward in the drug approval process, with the regulatory agency doing its due diligence before the distribution of the drug to patients." He noted that this approach follows the same regulatory pathway used for other drugs in this class, including Leqembi (lecanemab), which received traditional FDA approval in July 2023.
Innovative Trial Design and Biomarker Strategy
The TRAILBLAZER-ALZ 2 trial has been highlighted for its innovative approach to patient selection and treatment monitoring. Investigators employed what they termed a "goldilocks strategy" to identify patients in early stages of Alzheimer's disease who would most likely benefit from treatment.
A distinguishing feature of the trial was its use of both Amyvid® and Tauvid™ PET scans to enroll patients with confirmed amyloid plaques. This dual biomarker approach allowed researchers to confirm clearance or reduction of the pathology in subsequent scans, providing concrete evidence of the drug's mechanism of action.
Dr. Fillit emphasized that this biomarker-powered trial "exemplifies the importance of developing biomarkers and drugs in tandem to support drug development, trial enrollment, and target engagement."
The Evolving Alzheimer's Treatment Landscape
The potential approval of donanemab would add to the growing arsenal of disease-modifying treatments for Alzheimer's disease. Leqembi, developed by Eisai and Biogen, became the first anti-amyloid therapy to receive traditional FDA approval last year, marking a significant milestone in Alzheimer's treatment.
However, experts stress that anti-amyloid therapies represent just one approach to addressing this complex neurodegenerative disease. Currently, nearly 75% of Alzheimer's drugs in development are exploring novel targets related to various aging pathways, including inflammation, metabolic disturbances, and vascular dysfunction.
"Anti-amyloids are only one part of the solution," Dr. Fillit noted. "There remains a pressing need to develop the next generation of drugs and biomarkers targeting the various aging pathways that can be administered via a combination therapy and precision medicine approach."
Future Direction: Precision Medicine and Combination Therapies
The ultimate goal in Alzheimer's treatment is moving toward a precision medicine approach similar to cancer care, where therapies are tailored to each patient's individual biomarker profile. This would involve combining amyloid-clearing drugs with novel therapies targeting other disease pathways.
Early detection and intervention will be further supported by more accessible and scalable blood-based biomarkers. Two examples highlighted by the ADDF include ALZpath's pTau 217 assay and C2N Diagnostic's Precivity AD test, both of which received ADDF funding.
"It is crucial we build on recent momentum to move towards a future where we can halt the progression of Alzheimer's or prevent it altogether by addressing the complexity of the disease with an arsenal of novel drugs guided by the biology of aging," Dr. Fillit concluded.
The FDA advisory committee for donanemab is scheduled to take place later this year, with the date yet to be announced.
