The complete results of Part 1 of the Phase 2 study of MariTide (maridebart cafraglutide, formerly AMG 133), a long-acting peptide-antibody conjugate that is subcutaneously injected monthly or less frequently, were released today by Amgen (NASDAQ:AMGN). In addition to these findings, full findings from the primary analysis of the Phase 1 pharmacokinetics low dose initiation (PK-LDI) study assessing lower initial dosages of MariTide were concurrently published in The New England Journal of Medicine and presented as part of an expert-led Symposium at the 85th American Diabetes Association (ADA) 85th Scientific Sessions.
MariTide showed up to ~20% average weight loss in individuals with obesity who did not have Type 2 diabetes (T2D), compared to 2.6% in the placebo arm, and up to ~17% average weight loss in individuals with obesity who had T2D, compared to 1.4% in the placebo arm, according to the efficacy estimand in the Phase 2 study. One By 52 weeks, weight loss had not plateaued, suggesting that more weight loss was possible. MariTide showed a strong and long-lasting decrease in hemoglobin A1c (HbA1c) of up to 2.2%1 in individuals with obesity and type 2 diabetes in addition to significant weight loss. Improvements in pre-specified cardiometabolic markers, such as blood pressure, high-sensitivity C-reactive protein (hs-CRP), waist circumference, and certain lipid parameters, were also observed in conjunction with weight loss with MariTide.
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,
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.
Jay Bradner
The Phase 2 research found no new safety signals, and tolerance was in line with the GLP-1 class. The majority of gastrointestinal (GI)-related adverse events (AEs) were mild to severe in severity and were the most commonly reported. In addition to routine unsolicited adverse event reporting, the trial used a strict daily patient reporting instrument called the MINVR (modified index of nausea/vomiting/retching) to actively request the existence of specific GI symptoms. When dose increase was employed without sacrificing efficacy, gastrointestinal problems were less common and mostly restricted to the initial dosage. Compared to the non-dose escalation arms, the dose escalation arms had decreased discontinuation rates of MariTide due to GI AEs (up to 7.8%).
In this Phase 2 study, participants living with obesity treated with MariTide had substantial weight reduction at 52 weeks without reaching a weight plateau
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.
Ania Jastreboff
In addition to evaluating PK, the Phase 1 PK-LDI study evaluated several MariTide dose escalation plans using the MINVR reporting tool. According to the full primary analysis, the total incidence of vomiting was 22.5% for individuals who got 35 mg/70 mg/350 mg and 24.4% for those who received 21 mg/70 mg/350 mg. At no point during the research were there any discontinuations brought on by GI AEs.
The Phase 3 MARITIME program was informed by data from the Phase 1 and Phase 2 PK-LDI MariTide trials. The safety, effectiveness, and tolerability of MariTide will be assessed in patients with obesity or overweight who do not have Type 2 diabetes as part of the newly launched Phase 3 72-week chronic weight management trials. Over the course of an additional optimal eight-week dose escalation phase, participants will be randomized to one of three target doses, each with an initial beginning dose of 21 mg, followed by 35 mg, and finally 70 mg. Additionally, Amgen anticipates starting Phase 3 clinical outcomes studies for heart failure (HF) and atherosclerotic cardiovascular disease (ASCVD) in 2025, along with a Phase 3 trial for obstructive sleep apnea (OSA).
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