Novo Nordisk: Cagrisema shows ‘superior’ weight loss in REDEFINE 1 trial

Novo Nordisk (NVO) announced headline results from REDEFINE 1, a phase 3 trial in the global REDEFINE program. REDEFINE 1 is a 68-week efficacy and safety trial investigating subcutaneous CagriSema — a fixed dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg — compared to the individual components cagrilintide 2.4 mg, semaglutide 2.4 mg and placebo, all administered once-weekly. The trial included 3,417 randomized people with obesity or overweight with one or more comorbidities and a mean baseline body weight of 106.9 kg. The trial achieved its primary endpoint by demonstrating a statistically significant and superior weight loss at week 68 with CagriSema versus placebo. The REDEFINE 1 trial was based on a flexible protocol, allowing patients to modify their dosing throughout the trial. After 68 weeks, 57.3% of patients treated with CagriSema were on the highest dose compared to 82.5% with cagrilintide 2.4 mg and 70.2% with semaglutide 2.4 mg. When evaluating the effects of treatment if all people adhered to treatment, people treated with CagriSema achieved a superior weight loss of 22.7% after 68 weeks compared to a reduction of 11.8% with cagrilintide 2.4 mg, 16.1% with semaglutide 2.4 mg and 2.3% with placebo alone. In addition, 40.4% of patients who received CagriSema reached a weight loss of 25% or more after 68 weeks, compared to 6.0% with cagrilintide 2.4 mg, 16.2% with semaglutide 2.4 mg, and 0.9% with placebo. When applying the treatment policy estimand, people treated with CagriSema achieved a superior weight loss of 20.4% compared to a reduction of 11.5% with cagrilintide 2.4 mg, 14.9% with semaglutide 2.4 mg and 3.0% with placebo. In the trial, CagriSema, cagrilintide 2.4 mg and semaglutide 2.4 mg appeared to have a safe and well-tolerated 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. We are encouraged by the weight loss profile of CagriSema demonstrating superiority over both semaglutide and cagrilintide in monotherapy in the REDEFINE 1 trial. This was achieved even though only 57% of patients reached the highest CagriSema dose,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “With the insights obtained from the REDEFINE 1 trial, we plan to further explore the additional weight loss potential of CagriSema.” The results from the second pivotal phase 3 trial, REDEFINE 2, in adults with type 2 diabetes and either obesity or overweight are expected during the first half of 2025.