Maritide effects robust weight loss in people living with obesity or overweight at 52 weeks in a phase 2 study
According to phase 2 study, MariTide achieved significant weight loss in individuals with obesity or overweight, with up to ~20% loss in non-diabetics and ~17% in those with type 2 diabetes.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 2 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 1 pharmacokinetic study, additional dosing regimens have been evaluated in a planned preliminary analysis.
"We are very excited by MariTide's differentiated profile, with clinically meaningful attributes of substantial and progressive weight loss, monthly or less frequent dosing, significant improvements in cardiometabolic parameters and strong reduction of HbA1C," said Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen. "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."
Data from this Phase 2 study will be presented at a future medical congress and submitted for publication.
The ongoing Part 2 of the Phase 2 study is investigating MariTide beyond 52 weeks to evaluate further weight loss with continued treatment, weight maintenance through less frequent or lower dosing and durability of weight loss after discontinuation of MariTide. More than 90% of eligible patients chose to continue to participate in Part 2 of the study.
MariTide is expected to be delivered as a single dose in a convenient, handheld, patient-friendly, autoinjector device with a monthly or less frequent single-injection administration. MariTide is produced in Amgen's industry-leading manufacturing network.
Amgen is also advancing its obesity pipeline, which includes both oral and injectable approaches, composed of both incretin and non-incretin mechanisms.
About MariTide
MariTide is a bispecific glucagon-like peptide 1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist being investigated for the treatment of obesity and Type 2 diabetes mellitus. As a pioneering antibody-peptide conjugate molecule with a long half-life and dual mechanism of action, MariTide may allow for greater durability or reduce the likelihood of weight rebound after treatment stops. Pre-clinical studies have demonstrated that simultaneously activating GLP-1 and inhibiting GIP pathways had a stronger effect on weight loss than targeting either GLP-1 or GIP receptors alone. Amgen utilized its strong capabilities of human genetics to confirm the benefits of GIPR inhibition.
The clinical goal for people living with obesity or overweight is to achieve weight loss, and to maintain weight thereby improving health. Given the heterogeneity of obesity and the number of people impacted, a variety of approaches will be needed. In addition to MariTide, Amgen is also advancing an obesity pipeline, which includes both oral and injectable approaches, composed of both incretin and non-incretin mechanisms.
About the Phase 2 Study
The trial 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 2 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.
