Novo Nordisk files for FDA approval for CagriSema, the first once-weekly combination of GLP‑1 and amylin analogues

Novo Nordisk has submitted a New Drug Application (NDA) to the FDA for once-weekly CagriSema (cagrilintide 2.4 mg and semaglutide 2.4 mg) injection, to be used with a reduced-calorie diet and increased physical activity, to reduce excess body weight and maintain weight reduction long term in adults with obesity or overweight in the presence of at least one weight-related comorbid condition.

CagriSema is a fixed-dose combination of a long-acting amylin analogue, cagrilintide 2.4 mg, and the GLP-1 receptor agonist, semaglutide 2.4 mg.2 If approved, CagriSema would become the first injectable GLP-1 receptor agonist and amylin analogue combination treatment.

The NDA is based on results from REDEFINE 1, a 68-week, phase 3, randomised, double-blind, placebo-and active-controlled trial that evaluated the efficacy and safety of once-weekly, CagriSema compared to semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, or placebo, all as an adjunct to lifestyle intervention in 3,417 adults with obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/m2) with one or more obesity-related complications and without diabetes, and REDEFINE 2, a double-blind, randomised, placebo-controlled, 68-week, phase 3 trial that evaluated the efficacy and safety of once-weekly CagriSema versus placebo, as an adjunct to lifestyle intervention in 1,206 adults with type 2 diabetes and either obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/m2).

The REDEFINE 1 trial found that when evaluating the treatment effect regardless of whether patients stayed on treatment, those treated with CagriSema achieved weight loss of 20.4% (from an average baseline body weight of 236 lb) at 68 weeks versus 3.0% (from an average baseline body weight of 235 lb) for the placebo group which was statistically significant. CagriSema resulted in greater weight loss of 22.7% at 68 weeks versus 2.3% in the placebo group when evaluating the treatment effect if all patients stayed on treatment. 91.9% of participants taking CagriSema achieved a body weight reduction of greater than or equal to 5%, compared to 31.5% for the placebo group. In addition, a supportive secondary analysis showed that about half (54%) of trial participants with obesity at baseline treated with CagriSema reached the threshold for non-obesity (BMI <30 kg/m2) at week 68. In the placebo group, 11.1% reached that threshold at 68 weeks.

Safety data generated in the REDEFINE 1 and 2 trials was comparable with the GLP-1 RA class. Overall, discontinuation rates due to adverse events were low, with 5.9% for CagriSema versus 3.5% for placebo in REDEFINE 1 and 8.4% with CagriSema versus 3% with placebo in REDEFINE 2. In REDEFINE 1, adverse events were mainly gastrointestinal (79.6% in the CagriSema group vs 39.9% with placebo) including nausea (55% vs 12.6%), constipation (30.7% vs 11.6%), and vomiting (26.1% vs 4.1%).

The FDA is expected to review the CagriSema application in 2026.