Novo Nordisk A/S ( NVO ) stock fell on Monday after the company released topline results from the 2-year primary analysis of evoke and evoke+ phase 3 trials in early-stage symptomatic Alzheimer’s disease.

The two trials were randomised, double-blinded, enrolled 3,808 adults, and evaluated the efficacy and safety of oral semaglutide compared to placebo on top of standard of care.

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

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The evoke and evoke+ trials did not confirm superiority of semaglutide versus placebo in the reduction of progression of Alzheimer’s disease, as measured by the change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) score compared to baseline.

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.

In the evoke trials with patients aged 55-85, suffering from mild cognitive impairment or mild dementia due to Alzheimer’s disease, semaglutide appeared to have a safe and well-tolerated profile consistent with previous semaglutide trials.

To date, more than 37 million patient-years of semaglutide exposure have occurred across diverse patient populations.

The 1-year extension period in the evoke and evoke+ trials will be discontinued based on the efficacy results observed in the overall study population.

Novo launched the Alzheimer’s studies in 2021, following animal research and analyses of human data that suggested potential benefits.

A small study of liraglutide, the company’s older injectable GLP-1, also reported slower loss of brain volume in patients with mild Alzheimer’s.

The biological mechanisms remain unclear. GLP-1s may directly affect the brain, or the benefits could stem from weight loss and reduced inflammation.

Notably, all GLP-1 drugs are not identical; preclinical studies suggest that liraglutide enters the brain more readily than semaglutide.

Topline results from the evoke/evoke+ trials will be presented at the Clinical Trials in Alzheimer’s Disease (CTAD) conference on 3 December 2025, and full results at the 2026 Alzheimer’s and Parkinson’s Diseases Conferences (AD/PD) in March 2026.

Price Action: NVO stock was trading lower by 10.73% to $42.34 premarket at last check Monday.

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