Amgen Adjusts MariTide Dosing Strategy Following Phase 2 Trial Results

Amgen has released results from part 1 of its phase 2 study evaluating MariTide, its investigational weight-loss therapy, at the American Diabetes Association’s 85th Scientific Sessions in Chicago. The company simultaneously published the data in the New England Journal of Medicine. While the drug demonstrated considerable weight reduction in participants, the occurrence of gastrointestinal adverse events has prompted a modification in the dosing schedule for upcoming late-stage trials.

MariTide is a dual-acting compound that functions as a GLP-1 receptor agonist and GIP receptor antagonist. It was tested in individuals with obesity and in those with both obesity and type 2 diabetes. Patients with obesity experienced an average weight reduction of 16.2% from their baseline, while individuals with both conditions lost an average of 12.3% of their body weight.
When evaluating participants who remained on treatment through the full 52-week period, weight loss figures increased to 19.9% for those with obesity and 17% for patients with both conditions. According to Amgen, participants had not yet reached a weight-loss plateau at week 52, suggesting the potential for continued reduction.
However, a range of gastrointestinal side effects, especially nausea and vomiting, were reported throughout the trial. These events were more prominent in participants who began treatment with higher doses without prior dose escalation. Among the groups without dose escalation, early discontinuation due to side effects ranged from 12% to 27%. In contrast, those enrolled in dose-escalation arms had lower discontinuation rates, not exceeding 7.8%.
Vomiting occurred most frequently in the 420 mg every-eight-weeks group, with 92% of those participants reporting the symptom. The lowest rate of vomiting, 43%, was recorded in the four-week dose escalation group for patients with obesity. The side effects were primarily observed during the initial dosing phase.
Amgen confirmed that these outcomes, along with data from a phase 1 pharmacokinetics study using low-dose initiation, informed the structure of its ongoing phase 3 MARITIME program. Jay Bradner, M.D., Amgen’s executive vice president of research and development, stated: “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.”
The phase 3 studies, Maritime-1 and Maritime-2, will each span 72 weeks and assign patients to one of three target doses. All participants will begin with a 21 mg dose, which will be gradually increased to 35 mg and then 70 mg over eight weeks. These trials are expected to conclude in 2027.

Despite the data, Amgen’s shares dropped 5.8% following the ADA presentation. Some analysts, such as those from Jefferies, anticipate favorable phase 3 outcomes. However, Citi Research analysts expressed reservations, citing the impact of gastrointestinal events on the convenience factor of a monthly injectable therapy. Still, Amgen’s head of obesity, Susan Sweeney, described the dose-escalation method as “quite simple” and noted that it results in a manageable monthly regimen beneficial to primary care practices.
Looking ahead, Amgen plans to evaluate MariTide for potential use in conditions including atherosclerotic cardiovascular disease, heart failure, and obstructive sleep apnea, with a phase 3 trial for the latter planned for 2025.