In the phase 2, double-blind, randomized, placebo-controlled, dose-ranging trial (NCT05669599), maridebart cafraglutide (MariTide; Amgen), a long-acting, peptide-antibody conjugate subcutaneously administered monthly or less frequently for obesity treatment among individuals with type 2 diabetes (T2D), demonstrated up to 20% average weight loss without a weight loss plateau. The study authors, who presented their results at the 85th American Diabetes Association (ADA) Scientific Sessions and were published in The New England Journal of Medicine, noted that the therapy demonstrated meaningful weight loss and a sustained reduction in hemoglobin A1c (HbA1c) among individuals with obesity and T2D.1,2
Image credit: Rawpixel.com | stock.adobe.com
“[Maridebart cafraglutide] delivered strong efficacy, including sustained weight loss without a plateau in the 52-week Phase 2 study and meaningful improvements in cardiometabolic risk factors, representing a defining advance for the obesity field,” Jay Bradner, MD, executive vice president of research and development at Amgen, said in a news release.2
Indications for Maridebart Cafraglutide
As a long-acting peptide-antibody conjugate, maridebart cafraglutide combines glucagon-like peptide-1 receptor agonists (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonists (GIP) used to treat obesity. Previous preclinical studies have identified that activating GLP-1 and GIP pathways had a strong effect on weight loss compared to either receptor alone. The combination therapy could also cause greater durability or reduce the risk of weight regain after treatment concludes.2
Phase 2 Clinical Trial Results
A total of 592 individuals were included in the study and were divided into 2 cohorts. In cohort A, 465 individuals were included that were living with obesity or overweight without T2D, as 127 individuals in cohort B were living with obesity or overweight with T2D. In cohort A, individuals were randomly assigned to receive 1 of 4 monthly fixed-dose arms, including a placebo, 140 mg, 280 mg, or 420 mg, or an 8-week 420 mg dose arm. In cohort B, individuals were randomly assigned to receive 1 or 4 monthly fixed-dose arms, including a placebo, 140 mg, 280 mg, and 420 mg.1,2
Maridebart cafraglutide showed significant average weight loss in individuals with obesity, regardless of their T2D status. Specifically, individuals with obesity but without T2D experienced up to approximately 20% average weight loss with maridebart cafraglutide, compared to 2.6% in the placebo group. For individuals with obesity and T2D, maridebart cafraglutide led to up to approximately 17% average weight loss, while the placebo arm saw only a 1.4% reduction. Notably, the study observed that weight loss had not plateaued by 52 weeks, suggesting the possibility of even greater weight reduction with continued treatment.1,2
“In this Phase 2 study, participants living with obesity treated with [maridebart cafraglutide] had substantial weight reduction at 52 weeks without reaching a weight plateau,” Ania Jastreboff, MD, PhD, professor at Yale School of Medicine and director of the Y-Weight Yale Obesity Research Center, said in the news release.2
The therapy also demonstrated a reduction of up to 2.2% in HbA1c in individuals with obesity and T2D. Improvements in pre-specified cardiometabolic markers were also displayed, including reductions in waist circumference, improved blood pressure readings, decreased levels of high-sensitivity C-reactive protein, and positive adjustments in select lipid parameters.1,2
“Additionally, robust improvements in HbA1c were observed in participants who had [T2D] and obesity. These data demonstrate the potential for once-monthly or less frequent dosing and are particularly encouraging as we seek sustainable, long-term treatments for people living with obesity, with and without [T2D],” Jastreboff continued in the news release.2
The most reported adverse events were gastrointestinal-related and were mild to moderate in severity. However, no new safety signals were identified, and they were tolerable with the GLP-1 class.1,2
“These results, alongside the Phase 1 Pharmacokinetics Low Dose Initiation data, have shaped our Phase 3 MARITIME program. [Maridebart cafraglutide’s] monthly or less frequent dosing has the potential to improve adherence and long-term weight control, providing the opportunity to optimize health outcomes for people living with obesity, [T2D], and related conditions,” Bradner concluded in the news release.1