CagriSema helps women lose 25% of their weight in study

Novo continues to build the case for its new weight-loss candidate CagriSema, pointing to new data that show strong efficacy in women as it waits for an approval decision from the FDA in December.

The new findings come from an ad hoc analysis of the REDEFINE 1 study of CagriSema – a fixed-dose combination of Novo's GLP-1 agonist semaglutide and the amylin analogue cagrilintide – which rather disappointed when it was first revealed, as the 20.4% overall weight loss achieved across all patients came in below the 25% drop that had been signposted by the company as its expectation.

That picture was mirrored with the subsequent REDEFINE-2 readout, which revealed a topline 13.7% weight loss across the treatment arm, dashing hopes that CagriSema could be a strong successor to Novo's semaglutide-based Wegovy, which stands to lose patent protection in the early 2030s.

Since then, Wegovy has been overtaken in the injectable incretin market by Eli Lilly's rival GIP/GLP-1 agonist Zepbound (tirzepatide), which offers greater clinical efficacy than Novo's drug.

In the latest analysis, CagriSema achieved 25% weight loss on average in women with obesity or overweight after 68 weeks' treatment, compared to 3% with placebo, with significant reductions in abdominal fat, as measured by waist circumference.

The data also suggested that CagriSema was most effective in premenopausal women, who saw an average 26.7% reduction, with perimenopausal women achieving a 24.8% loss and postmenopausal women coming in at 23.1%. For placebo, the reductions came in at 2.1%, 1.7%, and 2.6%, respectively.

Novo noted that the hormonal shifts that occur with different stages of menopause can increase abdominal fat accumulation, which in turn can have an impact on body composition, weight, and cardiometabolic risk. "Reproductive stage is rarely evaluated as a factor in obesity research," said the company in a statement.

"Many women with obesity or overweight experience weight gain as they move through menopause, and it is important to explore investigational products such as CagriSema across the reproductive lifespan," said Michelle Skinner Moore, interim head of clinical development, medical and regulatory affairs at Novo.

"CagriSema has the potential to be the first amylin analogue and GLP-1 RA combination therapy for weight management, and these REDEFINE 1 data show it was associated with significant weight loss for women with obesity or overweight," she added.

Analyst estimates for CagriSema's sales potential are all over the place, particularly after Novo's gamble to run the head-to-head REDEFINE 4 trial of the drug against Zepbound failed to pay off, failing to show non-inferiority. Meanwhile, Lilly has reported impressive results with its Zepbound successor – GLP-1, GIP, and glucagon agonist retatrutide – which is being prepared for filing in the first quarter of 2027.

Since then, the company has been looking at differentiating CagriSema through flexible titration trial designs that could allow patients to lower doses due to side effects, as well as a higher-dose formulation that is being tested in the REDEFINE 11 study, which is due to generate results in the first half of next year.