Alzheimer’s Phase III miss signals GLP-1RA combination therapy potential
Posted: 25 November 2025 | Catherine Eckford (European Pharmaceutical Review) | No comments yet
Novo Nordisk is evaluating oral GLP-1 drug Rybelsus as a potential treatment in early symptomatic Alzheimer’s.
Rybelsus (oral semaglutide) did not demonstrate superiority of semaglutide versus placebo in delaying early Alzheimer’s disease progression, according to new phase III topline results from Novo Nordisk.
[The topline results] 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”
In the company’s two-year primary analysis of its phase III Evoke and Evoke+ trials, despite observed biomarker improvements, overall efficacy results mean the one-year extension period will be discontinued, Novo Nordisk confirmed.
Martin Holst Lange, Chief Scientific Officer and Executive Vice President of Research and Development at Novo Nordisk said: “Based on the significant unmet need in Alzheimer’s disease as well as a number of indicative data points, we felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success.”
The next era of Alzheimer’s drug development
Dr Howard Fillit, Co-Founder and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF), stated that despite the “disappointing” results, 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.”
As such, the data illustrates the preventative potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs), over their prospect in slowing disease progression.
Dr Fillit hopes that further results from the phase III trials being presented at the Clinical Trials in Alzheimer’s Disease (CTAD) conference on 3 December, will shed light on “a path forward for semaglutide as part of a combination therapy approach. Existing anti-amyloid drugs slow cognitive decline by around 30 percent, so therapies aimed at other pathways will be crucial as we chip away at the remaining 70 percent.”
Full results from the Evoke and Evoke+ trials will be presented at next year’s Alzheimer’s and Parkinson’s Diseases Conferences in March.
Despite this setback for Novo Nordisk, Eisai and Biogen’s antibody drug Leqembi recently received a new MHRA approval, granting its use as an IV maintenance therapy, providing an alternative Alzheimer’s treatment option.
Novo Nordisk’s Lange concluded: “While semaglutide did not demonstrate efficacy in slowing the progression of Alzheimer’s disease, the extensive body of evidence supporting semaglutide continues to provide benefits for individuals with type 2 diabetes, obesity, and related comorbidities.”
