Novo Nordisk’s vision of 25%-plus weight loss is looking further and further away. Three months after missing that target in its first phase 3 CagriSema trial, the Danish drugmaker has fallen even further short of that bar in the second study.
With Eli Lilly setting the pace on weight loss, Novo identified the fixed-dose combination CagriSema as a way to leapfrog its rival. Executives primed investors to expect patients taking the combination of amylin analogue cagrilintide and GLP-1 drug semaglutide to lose at least 25% of their body weight. Novo missed that target in its first phase 3 trial in December, causing investors to wipe 19% off its share price.
Despite the first trial lowering expectations, investors drove Novo’s share price down again in the wake of the release of data from the second trial. Patients in the second trial lost 15.7% after taking CagriSema weekly for 68 weeks. Weight loss after 68 weeks in the first trial was 22.7%. Weight loss in an analysis of the second trial that looked at treatment effect regardless of treatment adherence was 13.7%.
CagriSema easily beat placebo in both trials—weight loss on control was 3.1% in the second trial—but Novo needs to persuade patients and physicians to choose the combination over incumbent drugs. The phase 3 trials have failed to provide Novo with headline-grabbing efficacy to support its argument.
When Novo reported data from the first trial, it shared the percentage of patients—40.4%—who lost at least 25% of their body weight on CagriSema. That data point is missing from the readout on the second trial. Instead, Novo reported the percentage of people—89.7%—who lost at least 5% of their body weight. The second trial assessed weight loss of 5% or more after 68 weeks as a co-primary endpoint.
There are potential explanations for why weight loss was lower in the second trial than the first study. Patients in the second trial had Type 2 diabetes, unlike their counterparts in the first study, and on average were around 5 kg lighter at baseline. Even so, investors reacted badly to the data, sending Novo’s share price down 8% in trading in Copenhagen, Denmark.
William Blair analysts said today’s data was “especially disappointing” as they had believed adults with overweight or obesity as well as type 2 diabetes represented the patient segment where CagriSema has the best chance to outperform Eli Lilly’s Zepbound.
“It is our view that among investigated dual-acting agents (GLP-1/GIP, GLP-1/glucagon, GLP-1/amylin), the combination pursued by Eli Lilly’s Zepbound, Amgen’s MariTide, Viking’s VK2735 and Roche’s CT-388 likely represent the most promising approach to promote weight loss that can be generalized to the broadest population while retaining a manageable tolerability profile,” the analysts added in a March 10 note.
Novo was publicly more upbeat about the data than investors or analysts. Martin Holst Lange, M.D., Ph.D., executive vice president for development at Novo, said in a statement that the second trial “confirmed the superior efficacy of CagriSema in people with overweight or obesity and type 2 diabetes.” Novo plans to file for approval of CagriSema in the first quarter of 2026.
The company is also preparing to share data from the two trials. More detailed analyses could give a clearer look at the range of responses to CagriSema. Talking on an earnings call last month, Lange said the first trial revealed two groups. Some patients quickly went up to the maximum dose and achieved “very substantial weight loss,” Lange said, while others went slower to balance tolerability and efficacy.