CagriSema Achieves 22.7% Weight Loss in Phase 3 REDEFINE 1 Trial

Credit: Novo Nordisk

Topline data from the Phase 3 REDEFINE 1 trial found CagriSema, a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg, achieved superior weight loss versus placebo in adults with obesity or overweight.¹

Announced by Novo Nordisk on December 20, 2024, the trial achieved its primary endpoint with a superior weight loss of 22.7% after 68 weeks of treatment but still fell short of the ≥25% weight loss expected by the company in earlier discussions.

“We are encouraged by the weight loss profile of CagriSema demonstrating superiority over both semaglutide and cagrilintide in monotherapy in the REDEFINE 1 trial,” Martin Holst Lange, executive vice president for development at Novo Nordisk, said in a statement. “This was achieved even though only 57% of patients reached the highest CagriSema dose.”

The REDEFINE Phase 3 clinical development program comprises 2 pivotal trials enrolling approximately 4600 adults with overweight and obesity.² In REDEFINE 1, 3417 people with obesity or overweight and ≥1 comorbidity, with a mean baseline body weight of 106.9 kg, were randomized to once-weekly subcutaneous CagriSema, or to the individual components cagrilintide 2.4 mg, semaglutide 2.4 mg and placebo.

Based on a flexible dosing protocol, Novo Nordisk indicated patients could modify their dosing throughout the trial. After 68 weeks, 57.3% of the CagriSema cohort were on the highest dose, compared with 82.5% for cagrilintide 2.4 mg and 70.2% for semaglutide 2.4 mg.¹

In evaluating the effect of treatment adherence, those treated with CagriSema achieved a superior weight loss of 22.7% after 68 weeks, compared with a 11.8% reduction with cagrilintide 2.4 mg, 16.1% with semaglutide 2.4 mg and 2.3% with placebo alone.

Further analyses found that 40.4% of patients who received CagriSema achieved a ≥25% weight loss after 68 weeks, compared with 6.0% with cagrilintide 2.4 mg, 16.2% with semaglutide 2.4 mg, and 0.9% with placebo.

After measuring the treatment effect irrespective of adherence, Novo Nordisk reported 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.

Safety data regarding CagriSema found the drug appeared to be safe and well-tolerated, with most common adverse events being gastrointestinal-related. Most adverse events were identified by Novo Nordisk as mild to moderate and lessened over time, remaining consistent with other GLP-1 receptor agonists in the drug class.

Overall, these data matched, but did not exceed, the expected weight loss in the obesity drug market, particularly compared with Eli Lilly and Company's tirzepatide (Zepbound). Data from the SURMOUNT-1 trial found tirzepatide led to an average weight loss of ~23% in clinical trials.³ A recent head-to-head trial, SURMOUNT-5, found tirzepatide achieved a mean weight reduction of 20.2% versus 13.7% with semaglutide 2.4 mg (Wegovy).⁴

In the release, Novo Nordisk announced results from the second Phase 3 trial, REDEFINE 2, in adults with type 2 diabetes (T2D) and obesity or overweight are anticipated for the first half of next year.¹

“With the insights obtained from the REDEFINE 1 trial, we plan to further explore the additional weight loss potential of CagriSema,” Lange added.

References

1. _{CagriSema demonstrates superior weight loss in adults with obesity or overweight in the REDEFINE 1 trial. Novo Nordisk. December 20, 2024. Accessed December 20, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915082.}
2. _{A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight (REDEFINE 1). Clinicaltrials.gov. Accessed December 20, 2024. https://clinicaltrials.gov/study/NCT05567796?cond=obesity&term=REDEFINE+1&rank=1.}
3. _{Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038}
4. _{Campbell P. Surmount-5: Tirzepatide bests semaglutide in head-to-head weight loss trial. HCP Live. December 4, 2024. Accessed December 20, 2024. https://www.hcplive.com/view/surmount-5-tirzepatide-best-semaglutide-in-head-to-head-weight-loss-trial.}