Amgen Announces Robust Weight Loss With MariTide In People Living With Obesity at 52 Weeks in a Phase 2 Study

In people living with obesity or overweight without Type 2 diabetes,  The trial  (NCT05669599) enrolled 592 adults included two Cohorts of people living with obesity or overweight. Cohort A enrolled participants without a diagnosis of Type 2 diabetes, Cohort B participants had Type 2 diabetes. In Part 1, participants in Cohort A (n=465), without Type 2 diabetes, were assigned to one of four monthly fixed dose arms (placebo, 140 mg, 280 mg, 420 mg) or an 8-week 420 mg dose arm. There were also two dose escalation arms with either 4-week or 12-week dose escalation periods to a target dose of 420 mg. Adults in Cohort B (n=127), with type 2 diabetes, were assigned to one of four monthly fixed dose arms (placebo, 140 mg, 280 mg and 420 mg). At the end of Part 1, participants who met eligibility criteria (at least 15% weight loss at week 52 and still taking investigational product) had the option to enter Part 2 of the study. 

Part 2 of this Phase II  study is investigating MariTide beyond 52 weeks. In Part 2, Cohorts from Part 1 were pooled, then re-randomized based on their Part 1 doses to receive either placebo or a fixed monthly dose of 70 mg, 140 mg, 420 mg or a 12-week 420 mg dose. The purpose of Part 2 is to evaluate further weight loss with continued treatment, durable weight loss after discontinuation of MariTide and weight maintenance through less frequent or lower dosing.

MariTide demonstrated up to ~20% average weight loss at week 52 without a weight loss plateau, indicating the potential for further weight loss beyond 52 weeks. The study also showed people living with obesity or overweight and Type 2 diabetes, who typically lose less weight on GLP-1 therapies, achieved up to ~17% average weight loss, also without a weight loss plateau and lowered their average hemoglobin A1C (HbA1c) by up to 2.2 percentage points at week 52. In summary, in both study populations, a weight loss plateau was not observed, again indicating the potential for further weight loss beyond 52 weeks.

MariTide also demonstrated robust and clinically meaningful improvements in cardiometabolic parameters, including blood pressure, triglycerides and high-sensitivity C-reactive protein (hs-CRP) across doses. There were no significant increases in free fatty acids. 

There was no association between the administration of MariTide and bone mineral density changes. The most common adverse events (AEs) in the Phase II  study were gastrointestinal (GI) related, including nausea, vomiting and constipation. Nausea and vomiting were predominately mild, transient and primarily associated with the first dose. The incidence of nausea and vomiting was substantially reduced with dose escalation. In the dose escalation arms, for those with symptoms, nausea and vomiting were episodic; generally resolving within a median window of six days for nausea and one to two days for vomiting. The discontinuation rate in the dose escalation arms due to any AE was ~11% and less than 8% for GI-related events. No additional safety signals were identified. In a separate ongoing Phase I pharmacokinetic study, additional dosing regimens have been evaluated in a planned preliminary analysis.

Data from this Phase II  study will be presented at a future medical congress and submitted for publication.  More than 90% of eligible patients chose to continue to participate in Part 2 of the study. Based on these results Amgen plans to  start "MARITIME," a Phase iII program in obesity and obesity-related conditions.

Dr. Jay Bradner, Executive VP of R&D and CSO at Amgen said, "These results provide us confidence to initiate MARITIME, a Phase 3 program across obesity and a number of related conditions, providing a unique potential new treatment option for patients."