Obesity Drug MariTide Achieves Up to 20% Weight Loss in Phase 2 Trial

Positive 52-week Phase 2 data reported the benefit of maridebart cafraglutide (MariTide), an investigational antibody peptide conjugate formerly known as AMG 133, for individuals with obesity or overweight.¹

Announced by Amgen, on November 26, 2024, MariTide achieved up to a ~20% average weight loss without a weight loss plateau in people living with obesity or overweight without type 2 diabetes (T2D). Those with obesity or overweight and T2D achieved up to a ~17% average weight loss without a plateau.

"We are very excited by MariTide's differentiated profile, with clinically meaningful attributes of substantial and progressive weight loss, monthly or less frequent dosing, significant improvements in cardiometabolic parameters, and strong reduction of HbA1C," Jay Bradner, MD, Amgen’s chief scientific officer and executive vice president of research and development, said in a statement.¹

Global rates of obesity more than doubled in the past three decades, with approximately 2 in 5 adults (42.5%) in the US living with obesity.² Recognition of obesity as a chronic disease by the American Medical Association (AMA) transformed the care landscape, but only 1–3% of eligible adults are prescribed treatment for chronic obesity management.³

MariTide has been developed in Amgen’s obesity pipeline as a bispecific glucagon-like peptide 1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist.¹ Citing its longer half-life and dual mechanism of action, Amgen indicated MariTide could allow for greater durability and a lower risk of weight rebound after treatment cessation.

The Phase 2 trial enrolled 592 adults into 2 cohorts: Cohort A enrolled participants without a diagnosis of T2D (n = 465) and Cohort B enrolled those with T2D (n = 127). In Part 1 of the trial, participants in Cohort A were assigned to monthly fixed dose arms of placebo, MariTide 140 mg, 280 mg, and 420 mg, or an 8-week 420 mg dose arm.

Two dose escalation arms contained either 4-week or 12-week dose escalation periods to a target dose of 420 mg. Participants in Cohort B were assigned to monthly fixed dose arms of placebo or MariTide 140 mg, 280 mg, and 420 mg.

Both populations did not experience a weight loss plateau with MariTide treatment, suggesting the potential for further weight loss beyond 52 weeks. MariTide achieved clinically meaningful improvement in blood pressure, triglyceride levels, and high-sensitivity C-reactive protein across dose levels, without significant increases in free fatty acids or bone mineral density changes.

Safety outcomes showed the most common adverse events (AEs) in the Phase 2 study were gastrointestinal (GI) related, including nausea, vomiting, and constipation, notably reduced with dose escalation. Discontinuation in the dose escalation arm due to AEs was ~11% and ≤8% for GI-related events.

In the ongoing Part 2, the study will further evaluate the weight loss effects of MariTide beyond 52 weeks, weight maintenance through less frequent or reduced dosing, and the durability of weight loss after drug discontinuation. More than 90% of eligible patients continued to participate in Part 2, according to Amgen.

"These results provide us confidence to initiate MARITIME, a Phase 3 program across obesity and a number of related conditions, providing a unique potential new treatment option for patients,” Bradner added.¹

References

1. _{Amgen announces robust weight loss with Maritide in people living with obesity or overweight at 52 weeks in a phase 2 study. Amgen. November 26, 2024. Accessed November 26, 2024. https://www.amgen.com/newsroom/press-releases/2024/11/amgen-announces-robust-weight-loss-with-maritide-in-people-living-with-obesity-or-overweight-at-52-weeks-in-a-phase-2-study.}
2. _{Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief. 2020;(360):1-8.}
3. _{Kyle TK, Dhurandhar EJ, Allison DB. Regarding Obesity as a Disease: Evolving Policies and Their Implications. Endocrinol Metab Clin North Am. 2016;45(3):511-520. doi:10.1016/j.ecl.2016.04.004}