Biomarkers Bright, Outcomes Dim: Novo's Alzheimer's Bid Fails

Novo Nordisk (NVO) shares plunged to a multi-year low on Monday after the Danish pharmaceutical giant announced that its phase 3 trials testing semaglutide for Alzheimer's disease failed to meet their primary endpoint. The EVOKE and EVOKE+ trials, which enrolled 3,808 patients with early-stage Alzheimer's, showed no statistically significant slowing of disease progression compared to placebo, despite improvements in Alzheimer's-related biomarkers. The announcement sent Novo's stock tumbling over 9% in premarket trading, marking its steepest decline since July 2021.

The setback represents a major blow for Novo Nordisk, which had pinned hopes on expanding semaglutide-its flagship active ingredient in diabetes and obesity drugs like Ozempic and Wegovy-into the lucrative Alzheimer's market. The company's Chief Scientific Officer, Martin Holst Lange, acknowledged the disappointment, stating that while semaglutide remains effective for diabetes and obesity, it "did not demonstrate efficacy in slowing the progression of Alzheimer's disease". The trials had been widely regarded as a high-risk, high-reward opportunity, with UBS estimating just a 10% probability of success.

The market reaction extended beyond Novo. Eli Lilly shares fell 0.5% premarket as investors reevaluated the competitive landscape for GLP-1 drugs in neurodegenerative diseases. Conversely, Biogen's stock rose 2.7% as the shift in momentum opened new opportunities for its Alzheimer's treatments according to market analysis. Analysts noted that the failure underscores the challenges of repurposing metabolic drugs for neurological conditions, with Morgan Stanley's Thibault Boutherin having previously predicted a 75% chance of trial failure.

Novo Nordisk's struggles come amid a broader reckoning for the company. The drugmaker, which has seen its stock decline over 50% year-to-date, recently cut growth forecasts for its obesity drugs and faced intensifying competition from Eli Lilly's Zepbound and Mounjaro. The Alzheimer's setback adds to a difficult year marked by leadership changes, pricing pressures, and a $10 billion bid for obesity-drug developer Metsera according to financial analysts. "This is another headwind in an already challenging environment," said Erik Berg-Johansen, a portfolio manager at Storebrand Asset Management.

The company plans to present top-line results from the trials at the Clinical Trials on Alzheimer's Disease (CTAD) conference in December 2025, with full data expected at the AD/PD 2026 meeting according to company officials. While the failure closes a potential multi-billion-dollar growth avenue, Novo's core GLP-1 franchise remains intact. However, the outcome reinforces skepticism about the drug's versatility, with Bernstein analysts previously calling the Alzheimer's trial "a long shot".

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