Novo Nordisk has revealed that its Phase III trials of semaglutide (the active ingredient in Ozempic and Wegovy) did not demonstrate a statistically significant reduction in Alzheimer’s disease progression. 

The top-line results from the two-year primary analysis of evoke and evoke+ Phase III trials in early-stage symptomatic Alzheimer’s disease were announced on the company’s website. 

Novo’s share price dropped nearly 10% following the announcement, though recovered slightly throughout the day. It is further bad news for the struggling company, which recently lost out to competitor Pfizer on the acquisition of Metsera. 

The two trials enrolled 3,808 adults and evaluated the efficacy and safety of oral semaglutide compared to placebo on top of standard of care, measured by the change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) score compared to baseline. 

Novo says the decision to pursue an Alzheimer’s disease indication with semaglutide was based on real-world evidence studies, pre-clinical models as well as post-hoc analyses from diabetes and obesity trials. 

While treatment with semaglutide resulted in improvement of Alzheimer’s disease-related biomarkers in both trials, this did not translate into a delay of disease progression. 

“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,” said Martin Holst Lange, Chief Scientific Officer and Executive Vice President of Research and Development at Novo Nordisk. “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.” 

The one-year extension period in the evoke and evoke+ trials will be discontinued based on the efficacy results observed in the overall study population. 

Diana Turner, Deputy Editor, DDW