Investors appeared disappointed by CagriSema’s Phase III readout, which showed weight loss that fell short of Novo Nordisk’s prior projections for the therapy. Meanwhile, Eli Lilly’s stock rose on the news.
Novo Nordisk on Friday released headline data from the Phase III REDEFINE 1 trial of its next-generation weight-loss therapy CagriSema, touting “superior weight loss” in people with obesity and overweight than just cagrilintide, semaglutide (marketed as Wegovy for weight loss and Ozempic for diabetes) or placebo.
CagriSema’s performance fell short of Novo’s prior projections for its drug combo, however, and investors were not impressed. Novo is trading around 20% lower before the opening bell on Friday, while competitor Eli Lilly as well as other companies in the weight loss space, including Viking Therapeutics, Amgen, Biohaven and Structure Therapeutics traded higher in the premarket, Seeking Alpha reported.
In REDEFINE 1, Novo randomized more than 3,400 participants, all of whom had at least one weight-related comorbidity, to receive cagrilintide, semaglutide, CagriSema—a fixed-dose combination of the other two drugs—or placebo. All therapies were given once weekly, but the study adopted a flexible protocol that allowed patients to alter their dosing throughout the trial.
Results showed that participants in CagriSema lost 22.7% of their body weight at 68 weeks. Novo in its press announcement called this effect “statistically significant and superior” to cagrilintide and semaglutide, which elicited weight-loss of 11.8% and 16.1% at the same time point, respectively. Placebo controls dropped 2.3% of their weight at 68 weeks.
In addition, more than 40% of CagriSema-treated participants achieved weight loss of at least 25%, versus 6% of patients taking cagrilintide, 16.2% of those on semaglutide and 0.9% of participants in the placebo group.
“We are encouraged by the weight loss profile of CagriSema demonstrating superiority over both semaglutide and cagrilintide,” Martin Holst Lange, Novo’s executive vice president for development, said in a statement. “With these insights obtained from the REDEFINE 1 trial, we plan to further explore the additional weight loss potential of CagriSema.”
However, CagriSema’s performance was below the appoximately 25% weight loss Novo had expected, according to a report from Reuters last month.
“These results are roughly in line with what Lilly has demonstrated for tirzepatide (22.5% and 20.9% respectively at 72 weeks), but fall short of the 25% bar for efficacy many investors were anticipating,” BMO Capital Markets analysts wrote in a note to investors.
Thursday’s readout could cast an even longer shadow of doubt over Novo’s obesity pipeline, particularly after the disappointing Phase II results for its small molecule oral cannabinoid receptor 1 agonist monlunabant, which in September showed modest weight reductions muddied by psychiatric side effects.
Novo is under a lot of pressure to retain its leader status in the obesity space, especially amid the rapidly growing competition from other companies working on weight-loss medications. Chief of these is fellow frontrunner Eli Lilly, which earlier this month showed that Zepbound (tirzepatide) leads to greater weight-loss than Wegovy.
Lilly is also pulling ahead in terms of supply, with the FDA confirming on Thursday that the pharma’s tirzepatide brands are formally out of shortage—essentially disallowing compounders from producing their own remixed versions of the drug. Semaglutide, meanwhile, is still tagged as being in shortage by the FDA—even if all doses of Wegovy and Ozempic are marked as available on the regulator’s website.
Novo will continue studying CagriSema with its Phase III REDEFINE clinical development program. A second pivotal study, dubbed REDEFINE 2, is focusing on adults type 2 diabetes patients with either obesity or overweight. Initial data from this trial is expected in the first half of 2025.
