Overview
Amgen, announced full results from part 1 of the phase 2 study of MariTide (maridebart cafraglutide, formerly AMG 133), a long-acting, peptide-antibody conjugate subcutaneously administered monthly or less frequently. In addition to these data, complete results from the primary analysis of the phase 1 pharmacokinetics low dose initiation (PK-LDI) study evaluating lower starting doses of MariTide were presented as part of an expert-led Symposium at the 85th American Diabetes Association Scientific Sessions and simultaneously published in The New England Journal of Medicine.
Phase 2 trial of MariTide
- In the phase 2 study, MariTide demonstrated up to ~20% average weight loss in people living with obesity without type 2 diabetes (T2D) compared with 2.6% in the placebo arm, and up to ~17% average weight loss in people living with obesity with T2D, compared with 1.4% in the placebo arm, per the efficacy estimand.
- Weight loss had not plateaued by 52 weeks, indicating the potential for further weight reduction.
- In addition to meaningful weight loss, MariTide demonstrated a robust and sustained reduction in hemoglobin A1c (HbA1c) of up to 2.2% in people living with obesity and T2D.
- Weight loss with MariTide was also accompanied by improvements across pre-specified cardiometabolic measures, including waist circumference, blood pressure, high-sensitivity C-reactive protein (hs-CRP) and select lipid parameters.
Words from executive vice president: R&D, Amgen
- 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,"" said Jay Bradner, executive vice president of R&D at Amgen.
- These results, alongside the phase 1 Pharmacokinetics Low Dose Initiation data, have shaped our phase 3 MARITIME program. MariTide'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, type 2 diabetes and related conditions.""
Safety signals & adverse events
- No new safety signals were identified in the phase 2 study and tolerability was consistent with the GLP-1 class.
- The most frequently reported adverse events (AEs) were gastrointestinal (GI) related, and most were mild to moderate.
- The study employed a rigorous daily patient reporting tool known as the MINVR (modified index of nausea/vomiting/retching) to actively solicit the presence of select GI symptoms in addition to standard unsolicited AE reporting.
- Gastrointestinal events were predominantly limited to initial dosing and less frequent when dose escalation was used without compromising efficacy.
- Discontinuation rates of MariTide due to GI AEs in the dose escalation arms (up to 7.8%) were lower than non-dose escalation arms.
Expert comment from Ania Jastreboff
- In this phase 2 study, participants living with obesity treated with MariTide had substantial weight reduction at 52 weeks without reaching a weight plateau,"" said Ania Jastreboff, M.D., Ph.D., professor at Yale School of Medicine and director of the Y-Weight Yale Obesity Research Center.
- • Additionally, robust improvements in HbA1c were observed in participants who had type 2 diabetes 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 type 2 diabetes.""
Phase 1 PK-LDI Study Supports Tolerability of MariTide Dose Escalation
- The phase 1 PK-LDI study assessed PK and also used the MINVR reporting tool to assess different dose escalation schedules of MariTide.
- The complete primary analysis showed participants that received 21 mg/70 mg/350 mg had an overall incidence of vomiting of 24.4% and participants that received 35 mg/70 mg/350 mg had an overall incidence of vomiting of 22.5%.
- There were no discontinuations due to GI AEs at any time during the study.
Amgen Advances MariTide into Phase 3 MARITIME Program for Chronic Weight Management
- Data from Phase 1 (PK-LDI) and Phase 2 studies of MariTide have laid the foundation for the Phase 3 MARITIME program.
- The 72-week Phase 3 trials will assess the safety, efficacy, and tolerability of MariTide in adults with obesity or overweight, both with and without Type 2 diabetes.
- Participants will be randomized to one of three target doses, beginning at 21 mg, escalating to 35 mg, and then 70 mg over an eight-week optimized titration period.
- In addition to chronic weight management, Amgen plans to initiate Phase 3 outcome studies in 2025 for:
- Atherosclerotic cardiovascular disease
- Heart failure
- Obstructive sleep apnea
- These studies reflect Amgen’s commitment to expanding MariTide’s therapeutic impact across multiple cardiometabolic conditions.
