Amgen Reports Significant Weight Loss With MariTide in Obesity or Overweight Patients After 52 Weeks in Phase 2 Study

On November 26, 2024, Amgen, based in Thousand Oaks, California, shared encouraging results from a 52-week, double-blind, dose-ranging Phase 2 study involving MariTide (formerly AMG 133), a novel antibody peptide conjugate administered subcutaneously. MariTide, designed for monthly or less frequent administration, showed substantial weight reduction in individuals with obesity or overweight conditions, both with and without Type 2 diabetes.

Participants without Type 2 diabetes witnessed an average weight loss of around 20% at week 52 without reaching a plateau, suggesting the potential for continued weight loss beyond the 52-week mark. For those with Type 2 diabetes, who usually experience lesser weight loss with GLP-1 therapies, the study reported an average weight loss of approximately 17%, also without a plateau, alongside a notable decrease in average hemoglobin A1C (HbA1c) levels by up to 2.2 percentage points.

The study highlighted MariTide's significant positive impact on various cardiometabolic parameters, such as blood pressure, triglycerides, and high-sensitivity C-reactive protein (hs-CRP), with no significant rise in free fatty acids. Importantly, there was no link between MariTide administration and changes in bone mineral density.

The most frequently reported adverse events (AEs) were gastrointestinal-related, including nausea, vomiting, and constipation. These symptoms were mostly mild and transient, primarily associated with the initial dose. Nausea and vomiting episodes were significantly reduced with dose escalation, generally resolving within six days for nausea and one to two days for vomiting. The discontinuation rate due to any adverse event in the dose escalation arms was about 11%, with less than 8% for GI-related events, and no new safety concerns were identified.

MariTide's clinical benefit profile includes significant weight loss, improved cardiometabolic health, and notable HbA1c reduction. This establishes a strong case for advancing MariTide into the Phase 3 MARITIME program, encompassing obesity and related conditions, potentially offering a new treatment avenue for patients.

Currently, Part 2 of the Phase 2 study is exploring MariTide's effects beyond 52 weeks, aiming to evaluate ongoing weight loss with continued treatment, weight maintenance with less frequent or lower dosing, and the durability of weight loss post-treatment. Impressively, over 90% of eligible patients opted to continue into Part 2.

MariTide is anticipated to be administered in a user-friendly, handheld autoinjector device, delivering a single monthly or less frequent dose. Produced in Amgen’s leading manufacturing network, MariTide represents a significant advancement in obesity treatment.

Moreover, Amgen is progressing with its broader obesity treatment pipeline, which includes both oral and injectable therapies targeting multiple mechanisms, both incretin and non-incretin based.

Obesity, recognized as a complex disease, significantly raises the risk for various severe health conditions, including Type 2 diabetes, heart failure, kidney disease, sleep apnea, and several cardiovascular and metabolic disorders. The global prevalence of obesity has more than doubled from 1990 to 2022. In the U.S., over 42.5% of adults are reported to be living with obesity, and globally, 890 million adults were living with obesity in 2022, while 2.5 billion were overweight. Despite its widespread impact and recognition as a chronic disease, only a small fraction of affected individuals in the U.S. receive medication for chronic weight management.

MariTide, a bispecific GLP-1 receptor agonist and GIPR antagonist, stands out due to its dual mechanism of action and extended half-life, potentially offering more sustainable weight loss and reducing the likelihood of weight rebound after treatment cessation. Pre-clinical studies have shown that targeting both GLP-1 and GIP pathways simultaneously is more effective in weight loss than targeting either pathway alone. This innovative approach, bolstered by Amgen’s genetic research, supports the therapeutic potential of GIPR inhibition.

The Phase 2 study (NCT05669599) involved 592 adults divided into two cohorts: those without Type 2 diabetes and those with Type 2 diabetes. The study's first part assigned participants to different dosing regimens, including placebo, fixed doses, and dose escalation arms. The second part intends to further investigate MariTide's long-term efficacy, weight maintenance, and durability of weight loss.

This promising development in MariTide's clinical trial positions Amgen to potentially revolutionize obesity treatment, addressing a significant medical need with an innovative therapeutic solution.