Amgen Unveils Full Phase 2 Data on Monthly Obesity Drug MariTide, Highlighting Robust Weight Loss and Cardiometabolic Benefits at ADA 2024
Amgen has presented comprehensive results from the first part of its Phase 2 clinical trial investigating MariTide (formerly AMG 133, also known as maridebart cafraglutide), a novel subcutaneous, long-acting peptide-antibody conjugate designed to be administered monthly or even less frequently. These pivotal findings were unveiled at the 85th Scientific Sessions of the American Diabetes Association (ADA) and were concurrently published in The New England Journal of Medicine, underscoring the significant promise of MariTide in the growing field of anti-obesity therapies.
In tandem with the Phase 2 results, Amgen also shared detailed data from its Phase 1 Pharmacokinetics Low Dose Initiation (PK-LDI) study. This study explored the effects of beginning treatment with lower starting doses of MariTide to improve tolerability while maintaining clinical benefit. Both data sets now provide foundational insight into the design and direction of Amgen’s upcoming Phase 3 MARITIME clinical development program.
Phase 2 Study: Transformative Weight Loss and Glycemic Control
The Phase 2 trial focused on evaluating the efficacy and safety of MariTide in individuals with obesity, both with and without Type 2 diabetes (T2D). The data revealed compelling weight loss outcomes, particularly when compared to placebo. Patients without T2D who received MariTide experienced an average weight reduction of approximately 20% over 52 weeks, while the placebo group saw a modest 2.6% weight loss. In participants with T2D, the average weight loss with MariTide was around 17%, compared to just 1.4% in the placebo group.
Crucially, weight loss in the MariTide-treated groups had not plateaued at the 52-week mark, indicating the drug’s potential to drive continued weight reduction beyond one year. These results were evaluated using the efficacy estimand, a statistical model that accounts for treatment adherence and protocol deviations.
Beyond weight loss, MariTide also showed significant improvements in glycemic control. Among participants with T2D, the treatment was associated with a sustained reduction in hemoglobin A1c (HbA1c) levels of up to 2.2%, highlighting the dual metabolic benefits of the drug.
In addition, MariTide demonstrated favorable effects on key cardiometabolic risk markers, including:
- Waist circumference
- Blood pressure
- High-sensitivity C-reactive protein (hs-CRP)
- Lipid profiles
These changes suggest that the therapeutic impact of MariTide extends beyond weight loss alone, offering a broader cardiometabolic benefit that could translate into improved long-term health outcomes for individuals living with obesity and metabolic disorders.
Expert Perspective: A Potential Paradigm Shift in Obesity Treatment
Dr. Jay Bradner, M.D., Executive Vice President of Research and Development at Amgen, emphasized the broader implications of these findings.
“MariTide 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,” Bradner stated.
He added that these findings have directly informed the structure of the Phase 3 MARITIME program, and underscored the potential of MariTide’s monthly or less frequent dosing regimen to enhance adherence, sustainability, and long-term weight control.
This perspective was echoed by Dr. Ania Jastreboff, M.D., Ph.D., professor at Yale School of Medicine and director of the Y-Weight Yale Obesity Research Center.
“Participants living with obesity treated with MariTide had substantial weight reduction at 52 weeks without reaching a weight plateau,” she noted. “Additionally, robust improvements in HbA1c were observed in participants who had Type 2 diabetes and obesity. These data are particularly encouraging as we seek sustainable, long-term treatments for people living with obesity, with and without Type 2 diabetes.”
Safety Profile and Tolerability: No Surprises, GI Events Mostly Mild
In terms of safety, the Phase 2 study did not identify any new safety signals. The tolerability profile was consistent with the broader glucagon-like peptide-1 (GLP-1) receptor agonist class, known for gastrointestinal side effects. The most common adverse events (AEs) reported were GI-related, including nausea and vomiting, and were generally mild to moderate in severity.
To assess GI symptoms with precision, the study utilized a daily patient-reported outcome tool called the MINVR (modified index of nausea/vomiting/retching), in addition to standard unsolicited AE reporting. This allowed the team to actively monitor and quantify GI-related side effects.
Importantly, GI events were largely confined to the initial dosing phase and became less frequent when a dose escalation strategy was employed—a design element that maintained efficacy while enhancing tolerability. Notably, discontinuation rates due to GI side effects in dose-escalation arms were as low as 7.8%, compared to higher rates in non-escalation groups.
Phase 1 PK-LDI Study: Informing Dose Optimization
The Phase 1 PK-LDI study offered further insight into optimizing MariTide’s dose escalation approach. The study also incorporated the MINVR tool to rigorously evaluate tolerability across various dosing schedules.
Participants who received a dose regimen of 21 mg → 70 mg → 350 mg experienced a 24.4% incidence of vomiting, while those on the 35 mg → 70 mg → 350 mg regimen had a slightly lower incidence of 22.5%. Crucially, no participants discontinued the study due to GI-related adverse events, indicating that carefully managed dose escalation is effective in minimizing side effects while delivering therapeutic benefit.
These results played a crucial role in guiding the design of Amgen’s Phase 3 MARITIME program, ensuring that the chosen dosing strategy balances efficacy and patient comfort.
Ambitious Phase 3 Program Targets Multiple Conditions
Amgen’s Phase 3 development program for MariTide is already underway. The MARITIME program includes 72-week chronic weight management trials that will assess safety, efficacy, and tolerability in individuals with obesity or overweight, both with and without T2D.
Participants in these studies will be randomized across three target doses, beginning with an initial 21 mg dose, then escalating to 35 mg and finally 70 mg, over an optimized eight-week dose escalation period. This schedule reflects the learnings from the Phase 1 PK-LDI trial and aims to maximize tolerability while sustaining efficacy.
Beyond weight management, Amgen plans to initiate additional Phase 3 trials in 2025 to investigate MariTide’s potential in treating obesity-related comorbidities, including:
- Atherosclerotic cardiovascular disease (ASCVD)
- Heart failure (HF)
- Obstructive sleep apnea (OSA)
A Promising Candidate in the Evolving Obesity Treatment Landscape
The results shared by Amgen at ADA 2024 position MariTide as a compelling next-generation therapeutic in the fight against obesity and metabolic disease. With monthly or less frequent administration, robust and sustained weight loss, significant metabolic improvements, and a favorable safety profile, MariTide may address critical gaps in current obesity treatment paradigms.
As the Phase 3 MARITIME program gets underway, the pharmaceutical and medical communities will be watching closely to see if Amgen’s investigational agent can deliver on its early promise—and potentially reshape the standard of care for the millions affected by obesity worldwide.
