Novo Nordisk A/S (NVO) shares took a beating Monday after the pharmaceutical giant revealed that semaglutide—the blockbuster ingredient behind Ozempic and Wegovy—didn't deliver the hoped-for results in Alzheimer's disease trials.
The company released topline results from two massive Phase 3 trials, dubbed evoke and evoke+, which tracked 3,808 adults with early-stage symptomatic Alzheimer's disease over two years. Both were randomized, double-blinded studies that pitted oral semaglutide against placebo, with all participants continuing their standard Alzheimer's care.
Here's the kicker: while semaglutide improved Alzheimer's disease-related biomarkers in both trials, those biological improvements didn't actually slow down disease progression. The trials failed to show superiority versus placebo when measured by the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score, which tracks cognitive and functional decline from baseline.
Why Novo Thought This Might Work
The company didn't just throw darts at a board here. Novo launched these Alzheimer's studies back in 2021 based on some intriguing evidence: real-world data studies, preclinical animal models, and retrospective analyses from diabetes and obesity trials all suggested semaglutide might help with cognitive decline.
A smaller study of liraglutide—Novo's older injectable GLP-1 drug—even reported slower loss of brain volume in patients with mild Alzheimer's. The biological mechanisms remain murky, though. GLP-1 drugs might directly affect the brain, or the benefits could come indirectly through weight loss and reduced inflammation.
Interestingly, not all GLP-1 drugs are created equal. Preclinical research suggests that liraglutide crosses into the brain more readily than semaglutide, which might explain why the two drugs could have different effects on cognitive function.
Safety Profile Holds Up
There's a silver lining: in the evoke trials, which enrolled patients aged 55-85 with mild cognitive impairment or mild dementia due to Alzheimer's disease, semaglutide appeared safe and well-tolerated. The safety profile remained consistent with previous semaglutide trials. To date, more than 37 million patient-years of semaglutide exposure have been recorded across diverse patient populations.
What Happens Next
Based on these efficacy results, Novo will discontinue the one-year extension period that was planned for both trials. The company plans to present topline results at the Clinical Trials in Alzheimer's Disease (CTAD) conference on December 3, 2025, with full results coming at the 2026 Alzheimer's and Parkinson's Diseases Conferences in March 2026.
Novo Nordisk stock was trading down 10.73% to $42.34 in premarket trading Monday as investors digested the disappointing news.