The U.S. biotech company Amgen announced this week that its investigational drug maridebart cafraglutide (MariTide) has demonstrated weight loss in patients with obesity, overweight, and/or Type 2 diabetes, in a double-blind, dose-ranging Phase 2 study, enrolling 592 adults.
At 52 weeks, patients living with obesity or overweight showed an average of 20% average weight loss without a weight loss plateau, meaning there is a potential for further weight loss beyond this time. People with Type 2 diabetes with obesity or overweight, showed up to 17% average weight loss, also without a weight loss plateau. The company sees this as promising, stating that this patient population “typically lose(s) less weight on GLP-1 therapies.”
Moreover, the average hemoglobin A1C (HbA1c) was also lowered by up to 2.2 percentage points in people with Type 2 diabetes with obesity or overweight. HbA1c is a parameter showing blood glucose levels.
MariTide is a bispecific antibody-peptide conjugate, targeting the glucagon-like peptide 1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide receptor (GIPR), simultaneously. The drug is an agonist and acts as the naturally-occurring GLP-1 and GIP hormones do.
GLP-1 has several roles in the body including stimulating insulin release from the pancreas, preventing the secretion of glucagon to lower blood glucose levels, slowing down stomach digestion, and raising satiety. The release of GIP as a result of high glucose activates insulin secretion to lower blood glucose levels.
A number of different drugs, such as Novo Nordisk’s Ozempic, target either the GLP-1 or GIP receptor. Like Eli Lilly’s Mounjaro/Zepbound (tirzepatide), MariTide targets both receptors simultaneously, thereby having a stronger weight loss effect, as suggested by preclinical studies. Next to the dual mechanism of action, the antibody-peptide combination also gives the drug a longer half-life, allowing for greater durability and a lower likelihood of weight rebound when the treatment stops.
“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, Executive Vice President of Research and Development and Chief Scientific Officer at Amgen, in a press release.
The second part of the ongoing Phase 2 study is observing the effect of MariTide beyond 52 weeks. Patients will receive either a placebo, a 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,” the company wrote in a press statement.
Based on the current results, Amgen is planning to initiate a Phase 3 study called MARITIME, across obesity and several obesity-related conditions.
GLP-1 weight loss drugs are currently in vogue. However, companies are now clamoring to meet the growing demand and prevent manufacturing shortages. For example, the U.S. CDMO Corden Pharma recently announced that it will be expanding its GLP-1 manufacturing platform with a €900 million investment, while Eli Lilly is partnering with Amazon to enable better access to its weight loss medication.