Novo Nordisk’s Semaglutide Misses Key Goals in Closely-Watched Alzheimer’s Disease Phase 3 Trials

Novo Nordisk's oral semaglutide (Rybelsus), tested in the EVOKE and EVOKE+ phase 3 trials for early Alzheimer’s disease, failed to show statistically significant slowing of disease progression versus placebo2 3 4.

The trials aimed to demonstrate at least a 20% slowing in cognitive decline, but did not achieve superiority to placebo using primary endpoints such as change in the Clinical Dementia Rating – Sum of Boxes (CDR-SB)3 4.

While some Alzheimer’s disease-related biomarkers improved with semaglutide treatment, these changes were not sufficient to translate into meaningful clinical outcomes or delayed progression1 2.

Based on the disappointing efficacy results, Novo Nordisk is discontinuing the planned one-year extension phase of both trials and ending their Alzheimer’s development program for this drug2 3 4.

Novo Nordisk's stock price dropped sharply following the trial results, erasing hopes that the company’s GLP-1 drug platform could be expanded to Alzheimer’s beyond its current success in diabetes and obesity4 5.

The failure is considered a significant setback for both Novo Nordisk and the broader concept of using GLP-1 agonists to treat Alzheimer’s disease, with experts suggesting the results provide 'virtually no benefit' for slowing disease progression3 4.