Novo Nordisk’s obesity drug CagriSema disappoints again

Novo Nordisk A/S’ CagriSema combines the peptidic GLP-1 receptor agonist semaglutide, used in blockbuster weight-loss drug Wegovy, with dual amylin and calcitonin receptor agonist cagrilintide.

While the Phase III Redefine 1 trial met the primary endpoint with a weight loss of 22.7% versus 11.8% with semaglutide after 68 weeks of treatment, Redifine II achieved a superior weight loss of 15.7% compared to 3.1% with standard therapy. Weight loss of 5% or more after 68 weeks was a co-primary endpoint and was achieved by 89.7% of patients on CagriSema, compared to 30.3% by standard of care, semaglutide. In December 2024, Novo had set a 25% weight loss reduction as a goal for the experimental drug combo. Novo shareholder Markus Manns said, “Novo’s main mistake was to set expectations for CagriSema too high.” Novo‘s  successor to GLP-1 treatment standard Wegovy is on par with Eli Lilly‘s’s GLP1/GIP receptor agonist Mounjaro, giving Lilly an edge over Novo in the obesity market. However, all Big Pharma companies including Swiss Roche AG have licenced obesity candidates to participate in the obesity market race.

REDEFINE II enrolled included 1,206 obese or type II diabetics with a mean baseline body weight of 102 kg. The drug combo showed an acceptable safety toleratebility profile. The most common adverse events with CagriSema were gastrointestinal, and the vast majority were mild to moderate and diminished over time, consistent with the GLP-1 receptor agonist class.

Novo Nordisk expects to file for the first regulatory approval of CagriSema in the first quarter of 2026. The detailed results from REDEFINE 1 and REDEFINE 2 will be presented at a scientific conference in 2025.

REDEFINE is a Phase III programme with once-weekly subcutaneous CagriSema in obesity that consists of two pivotal Phase III 3 studies, which have enrolled approximately 4,600 adults with overweight or obesity. The programme includes:

REDEFINE 1 – a 68-week efficacy and safety Phase III trial of once-weekly CagriSema, cagrilintide 2.4 mg and semaglutide 2.4 mg versus placebo in 3,417 adults with obesity or overweight with one or more comorbidities and without type 2 diabetes.

REDEFINE 2 – a 68-week efficacy and safety Phase III trial of once-weekly CagriSema versus placebo in 1,200 adults with type 2 diabetes and either obesity or overweight.

REDEFINE 3 – an event-driven cardiovascular outcomes Phase III trial of once-weekly CagriSema versus placebo in 7,000 adults with established cardiovascular disease with or without type 2 diabetes.

REDEFINE 4 – an 84-week efficacy and safety Phase III trial of once-weekly CagriSema versus once-weekly tirzepatide 15 mg in 800 adults with obesity.

The process of converting white storage fat into energy-consuming brown fat cells is still at an early stage. A gene therapy approach, which has to be administered several times but has the advantage over all other approaches of not contributing to muscle loss, has already been earmarked by Sanofi via an equity investment. Obesity is the cause of many cardiovascular co-morbidities and thus is interesting to health systems.