Readout of Phase 3 Semaglutide Trials Marks Critical Moment in Alzheimer's Research and Suggests Potential for Combination Therapies
Data provides new insights into targeting the diverse pathobiology of Alzheimer's disease, an approach spearheaded by the ADDF
NEW YORK, Nov. 24, 2025 /PRNewswire/ -- Today, Novo Nordisk released topline results from their phase 3 Evoke and Evoke+ trials of semaglutide, an oral GLP-1 drug, in individuals with early-stage Alzheimer's disease, showing the trials did not meet their primary endpoints. The completion of these noteworthy phase 3 Alzheimer's studies, evaluating a mechanism grounded in the biology of aging, signifies the next era of Alzheimer's drug development – one that targets the disease's underlying pathobiology and reflects its true complexity.
"While it is disappointing that the trials did not meet their primary endpoints, they show a fundamental shift in how we approach the development of new Alzheimer's treatments, expanding beyond amyloid to target the complete pathobiology of the disease," said Howard Fillit, MD, Co-Founder and Chief Science Officer of the Alzheimer's Drug Discovery Foundation (ADDF). "Novo has noted an improvement of Alzheimer's-related biomarkers in both trials. We look forward to seeing further results at CTAD, as this may suggest a path forward for semaglutide as part of a combination therapy approach. Existing anti-amyloid drugs slow cognitive decline by around 30%, so therapies aimed at other pathways will be crucial as we chip away at the remaining 70%. The completion of two phase 3 trials targeting one of these pathways represents real momentum toward the kind of combination approach that has already transformed cancer care."
Running clinical trials aimed at the pathobiology of Alzheimer's remains critical as we move toward making a greater impact on slowing this disease. Although the Evoke and Evoke+ trials did not meet their primary endpoints, the metabolic pathway still holds promise.
The ADDF played a pivotal role in laying the groundwork for the semaglutide trial, investing nearly $1 million beginning in 2011 in a pioneering phase 2 study of liraglutide – an early generation injectable GLP-1 medication – conducted by Paul Edison, MBBS, PhD, FRCPI, Professor of Neuroscience in the Faculty of Medicine at Imperial College London. This early investment not only advanced understanding of GLP-1 mechanisms in the brain, but also catalyzed subsequent funding from Novo Nordisk and GE HealthCare, paving the way for today's landmark phase 3 trials.
"Alzheimer's is a complex condition that will ultimately require precision medicine, with treatment and prevention approaches tailored to each patient's unique biomarker profile," Dr. Fillit added. "Novo Nordisk's trial helps chart the path forward, demonstrating how rigorous studies targeting Alzheimer's pathobiology can expand our understanding of the disease and guide the development of combination therapies to enable earlier and more effective interventions than ever before. With more than 70% of the Alzheimer's pipeline now focused on novel targets, we are poised to shape a new era of science."
Further topline results from the Evoke and Evoke+ trials will be presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference in San Diego on December 3rd at 5:05pm PST.
About The Alzheimer's Drug Discovery Foundation (ADDF)
Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer's Drug Discovery Foundation is dedicated to rapidly accelerating the development of drugs to prevent, treat, and cure Alzheimer's disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer's, employing a venture philanthropy model to support research in academia and the biotech industry. The ADDF's leadership and contributions to the field have played a pivotal role in bringing the first Alzheimer's PET scan (Amyvid®) and blood test (PrecivityAD®) to market, as well as fueling the current robust and diverse drug pipeline. Through the generosity of its donors, the ADDF has awarded more than $370 million to fund 765 Alzheimer's drug development, biomarker, and prevention programs in 21 countries. To learn more, please visit: http://www.alzdiscovery.org/.
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SOURCE Alzheimer's Drug Discovery Foundation