“We felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success,” Martin Holst Lange, Novo’s R&D chief, said on Monday.
Novo Nordisk’s semaglutide did not reduce Alzheimer’s disease progression in a pair of Phase III trials, the company announced Monday. The unsuccessful trial results deal a blow to the theory that the GLP-1 weight loss and diabetes medication could open up a new frontier in care for the devastating neurodegenerative disease.
Stifel called the failures “very definitive” in an early morning note that spoke to the impact on Biogen, which along with Eisai markets Leqembi for Alzheimer’s.
BMO Capital Markets, meanwhile, put the fail in the larger context of Novo’s difficult 2025.
“While we had always viewed EVOKE/EVOKE+ as a higher risk, high reward opportunity for investors, NVO shares could see more significant downward volatility than otherwise expected as today’s miss adds to a list of recent struggles from the company,” the firm wrote Monday morning. The analysts noted the Metsera acquisition miss, guidance cuts and layoffs as Novo’s recent struggles that would have investors taking the Alzheimer’s news hard.
Novo’s shares plunged nearly 10% to $42.93 in pre-market trading on Monday. Biogen, meanwhile, saw a more than 4% rally to $183.51. Novo’s fierce rival in the GLP-1 space, Eli Lilly, also has an Alzheimer’s drug called Kisunla, but the company’s shares were stable on Monday.
Semaglutide, which Novo markets as Wegovy for weight loss and Ozempic for diabetes, was not superior to placebo in reducing the progression of disease, according to a Monday press release. The studies, called EVOKE and EVOKE+, enrolled 3,808 adults with mild cognitive impairment or mild dementia due to Alzheimer’s disease. Novo had embarked on the studies after real world evidence suggested semaglutide could have an impact.
Novo did report an improvement in Alzheimer’s biomarkers, but there was otherwise no clinically meaningful effect.
“Based on the significant unmet need in Alzheimer’s disease as well as a number of indicative data points, we felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success,” Martin Holst Lange, Novo’s chief scientific officer and executive vice president of R&D, said in the company’s statement. “We are proud to have conducted two well-controlled phase 3 trials in Alzheimer’s disease that meet the highest standards of research and rigorous methodology.”
Prior to the readout, analysts and investors had been keenly awaiting the news from Novo’s presentation at the Clinical Trials in Alzheimer’s Disease (CTAD) conference, slated for early next month. Novo went into the study with supportive mechanistic rationale, BMO said. But the studies were always a risk given the limited understanding of Alzheimer’s disease and how GLP-1s could help.
“Success likely would have been a meaningful positive, changing the potential commercial landscape for Alzheimer’s treatment and long-term revenue expectations for semaglutide,” BMO wrote. "[The] results are clearly disappointing, both for Novo and the broader Alzheimer’s community.”
Novo will discontinue a one-year extension of the trials. The company will present topline results at CTAD on December 3.
BMO noted that the biomarker results could suggest a longer-term impact may be possible with semaglutide.
“Results clearly represent a step back in what could have been a breakthrough for the field, but future study may still be necessary to further understand how results may differ with presymptomatic treatment over a longer time horizon,” the analysts said.
