China-based Innovent Biologics, Inc. (HKG: 1801) has announced that the results of the higher-dose cohorts in a Phase Ib study for mazdutide (IBI362), a glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, in overweight or obese Chinese participants have been published online at eClinicalMedicine.
Licensing Deal and Drug Profile
Innovent struck a licensing deal with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as mazdutide, IBI362, or LY3305677), a dual GLP-1 and glucagon receptor agonist, in China. Mazdutide is a long-acting synthetic peptide related to mammalian oxyntomodulin (OXM), which uses a fatty acid side chain to prolong the duration of action and allow once-weekly administration. Mazdutide is thought to exert its biological effects by activating the GLP-1 and glucagon receptors in humans, which is expected to improve glucose tolerance and induce weight loss, mimicking the effects of endogenous oxyntomodulin.
Clinical Study Results
The randomized, placebo-controlled multiple-ascending-dose study is designed to assess the safety, tolerability, and pharmacokinetic/pharmacodynamic characteristics of mazdutide in overweight or obese Chinese participants (NCT04440345). The results of lower-dose (3 mg, 4.5 mg, 6.0 mg) cohorts were published in eClinicalMedicine in August 2021. In higher-dose cohorts, 12 participants in each cohort were randomized 2:1 to receive subcutaneous 2.5-5.0-7.5-10.0 mg (10 mg cohort) or 3.0-6.0-9.0 mg (9 mg cohort) of mazdutide or a placebo once weekly, with each dose level administered for 4 weeks. In higher-dose cohorts, mazdutide up-titrated to 10 mg and 9 mg were both well tolerated. No participant discontinued the study due to adverse events. No serious adverse event or severe adverse event was reported. The most commonly reported treatment-emergent adverse events were gastrointestinal adverse events, mostly mild in severity.
At week 16, the mean reduction (percent reduction) from baseline in body weight was 7.62 kg (9.5%) for participants receiving mazdutide in the 10 mg cohort. At week 12, the mean reduction (percent reduction) from baseline in body weight was 9.23 kg (11.7%) for participants receiving mazdutide in the 9 mg cohort. Improvements in BMI, waist circumference, blood pressure, lipid, and serum uric acid were similar to those observed in the low-dose cohorts.
Future Development
Multiple clinical studies for mazdutide are ongoing, including the higher-dose cohort of a Phase II study of mazdutide in Chinese adults with obesity, with first participant dosing completed in September 2022 and a Phase III clinical study in Chinese adults with overweight or obesity initiated, which received IND approval in October 2022.-Fineline Info & Tech
