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Novo Nordisk (NVO) is plunging lower after announcing that its EVOKE and EVOKE+ Phase 3 trials of oral semaglutide did not demonstrate a statistically significant reduction in Alzheimer’s disease progression versus placebo. The company said the two-year primary analysis failed to meet the prespecified primary endpoint (CDR-SB), and a planned one-year extension was discontinued.

• The primary endpoint -- change in Clinical Dementia Rating–Sum of Boxes (CDR-SB) -- showed no meaningful slowing of cognitive or functional decline versus placebo, making the readout clearly negative and clinically disappointing.
• While semaglutide produced improvements in some Alzheimer’s-related biomarkers, those biomarker shifts did not translate into real-world clinical benefit, which is the key disconnect that explains today’s sharp market reaction.
• EVOKE and EVOKE+ enrolled about 3,800 patients with early-stage Alzheimer’s, and hopes were elevated because GLP-1 drugs have been associated with anti-inflammatory effects that some believed could slow neurodegeneration.
• An approval would have unlocked a major new non-core revenue stream on top of semaglutide’s already massive diabetes/obesity franchises, so today’s miss removes a meaningful upside scenario from the long-term model.
• The setback also has broader sector implications: it tempers enthusiasm for GLP-1-based approaches in neurodegeneration and may shift sentiment toward companies pursuing other mechanisms, such as Biogen’s (BIIB) work in amyloid and tau.

Briefing.com Analyst Insight:

NVO’s failure in EVOKE underscores how difficult it is to convert promising biomarker signals into meaningful clinical outcomes in Alzheimer’s disease. Even though the underlying scientific rationale for GLP-1s in neuroinflammation was compelling, the Phase 3 data show that the metabolic and anti-inflammatory effects of semaglutide weren’t enough to slow cognitive decline in early-stage patients. For NVO, the direct financial impact is limited because Alzheimer’s was not embedded into near-term forecasts, but the loss of optionality shrinks long-term upside and removes a sentiment driver for a stock already facing heightened expectations. The readout will also prompt investors to reassess the broader thesis that GLP-1 drugs could become a multi-disease platform beyond diabetes and obesity.