Novo Nordisk says oral semaglutide failed to slow early Alzheimer's in two large trials

Novo Nordisk said on Nov. 24 that oral semaglutide did not slow the progression of early Alzheimer's disease in two phase 3 trials, and the company's shares fell sharply on the news ^[1][2].

The studies, called EVOKE and EVOKE+, enrolled a combined 3,808 patients aged 55 to 85 who had mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's dementia, confirmed by amyloid testing ^[1][2]. Both missed their primary endpoint, a clinical dementia rating sum of boxes score measured at week 104, roughly two years into treatment ^[1]. Trial details show the studies were aiming for a 20% slowing of cognitive decline ^[2].

Novo said there was no delay in disease progression, but it also said improvements in disease-related biomarkers appeared in both trials, without saying which ones ^[1][2]. The company did not release figures. It said it will present topline data on Dec. 3 at the Clinical Trials in Alzheimer's Disease conference and full results in March 2026 at the Alzheimer's and Parkinson's Diseases Conference in Copenhagen ^[1][2]. Novo also said it will discontinue a planned one-year extension of the trials ^[1].

The medicine tested was Rybelsus, an oral semaglutide pill approved only for type 2 diabetes. It contains the same active ingredient as Ozempic and Wegovy ^[2]. The Rybelsus trials were the first large studies testing GLP-1 drugs in people with early-stage Alzheimer's ^[2].

Erik Berg-Johnsen, a portfolio manager at Novo shareholder Storebrand Asset Management, told Reuters that stopping after two years despite the planned third-year extension "suggests that semaglutide offers virtually no benefit in slowing Alzheimer's progression" ^[2]. Novo CEO Mike Doustdar said in a video posted on LinkedIn that the company's "efforts to slow down the progression of Alzheimer's disease have come to an end," adding that Novo had always known the chance of success was low ^[2].

Reuters reported the shares fell more than 12% before closing down 5.8% ^[2]. FiercePharma reported the stock was down nearly 9% at the U.S. market open and still down 6% by 11:30 a.m. EST ^[1]. UBS had estimated a 10% probability of success before the readout ^[2]. Several analysts called the drop an overreaction, including Simon Baker of Redburn Partners, who called it a "horribly overdone kneejerk reaction" that "could not be justified on any fundamental basis" ^[1]. Sydbank analyst Soren Lontoft Hansen attributed it to "the bad sentiment around the Novo Nordisk share and the negative news flow over the past year" ^[1][2].

The Alzheimer's Association said it was disappointed but that research would continue. "Though this semaglutide pill did not help against Alzheimer's, the field will continue to investigate this class of drugs, as they may act differently," it said ^[2]. Association president Joanne Pike said the results "will contribute to our understanding of this devastating and fatal disease" ^[2].

Why it matters for patients

Alzheimer's disease and other dementias affect more than 55 million people globally, and there is no cure ^[2]. The results do not change any approved use of semaglutide. Rybelsus remains approved for type 2 diabetes, and Ozempic and Wegovy keep their own approved diabetes and weight-related uses ^[2]. The announced findings do not point to a safety problem with the drug in these trials; the question was whether it slowed Alzheimer's, and it did not ^[1][2].

Two treatments are approved in the United States to slow Alzheimer's progression: Eisai and Biogen's Leqembi and Eli Lilly's Kisunla. Both require infusions or injections and can cause significant side effects ^[2].

Whether the biomarker changes Novo mentioned mean anything for patients has not been established, and the trial numbers behind that statement have not been released ^[1][2]. Alzheimer's trials have mostly ended in failure, and Eli Lilly has not tested its GLP-1 drug for Alzheimer's ^[2].

What happens next

Novo will release topline numbers from both trials on Dec. 3 at the Clinical Trials in Alzheimer's Disease conference, with full results in March 2026 at the Alzheimer's and Parkinson's Diseases Conference in Copenhagen ^[1][2]. The one-year extension study is being discontinued ^[1]. The Alzheimer's Association said the field will keep investigating this class of drugs ^[2]. Separately, Johnson & Johnson said days earlier that its anti-tau antibody posdinemab failed to significantly slow clinical decline in a mid-stage study, and the company ended that trial ^[1].