Innovent Biologics, Inc. (Innovent) announced that the first participant has been successfully dosed in a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial (DREAMS-1) of mazdutide (Innovent R&D Code: IBI362), a glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese patients with type 2 diabetes. This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical study to evaluate the efficacy and safety of mazdutide in Chinese patients with type 2 diabetes inadequately controlled by diet and exercise alone (ClinicalTrials.gov, NCT05628311). The study plans to enroll approximately 300 subjects, randomized in a 1:1:1 ratio, to receive either mazdutide 4.0 mg, mazdutide 6.0 mg or placebo.

The study treatment period will be 48 weeks in total, including a 24-week double-blind treatment period and a 24-week extension treatment period. The primary endpoint will be the change from baseline to week 24 in glycated hemoglobin (HbA1c) levels. In a phase 2 clinical study of mazdutide in Chinese patients with type 2 diabetes(ClinicalTrials.gov, NCT04965506), mazdutide was well tolerated and the overall safety profile was similar to other GLP-1 class drugs.

The mean change in HbA1c from baseline to week 20 was up to -1.67% with mazdutide (0.03% with placebo and -1.35% with dulaglutide). The mean change in body weight from baseline to week 20 was up to -7.11% with mazdutide (-1.38% with placebo and -2.69% with dulaglutide). In the study, mazdutide also offered multiple metabolic benefits to subjects, including reduced blood pressure, blood lipids and liver enzyme levels.

The DREAMS-1 study will further evaluate the long-term efficacy and safety of mazdutide in Chinese patients with type 2 diabetes inadequately controlled by diet and exercise alone. The prevalence of diabetes among adults in China is 11.6%, of which type 2 diabetes accounts for about 90% of the total number of diabetic patients, and the number of patients is still increasing. Poor glycemic control will lead to irreversible microvascular and macrovascular complications such as decreased visual acuity, blindness, renal insufficiency, peripheral neuropathy, myocardial infarction, stroke, amputation, etc.

As a latent disease with serious complications and high incidence, diabetes mellitus has seriously threatened human health. Currently, there are many treatment options for diabetes, and in addition to effective glycemic control, the development of new hypoglycemic drugs may also provide additional benefits for diabetic patients in terms of weight loss and cardiovascular risk reduction. Innovent entered into a licensing agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as mazdutide), a GLP-1R and GCGR dual agonist, in China.

In parallel, Lilly is developing OXM3 outside China. Mazdutide is a long-acting synthetic peptide related to mammalian oxyntomodulin (OXM) with a fatty acid side chain attached thereto. Mazdutide exhibits a prolonged duration of action allowing for once-weekly administration.

Mazdutide is thought to exert its biological effects by activating the GLP-1 receptor and glucagon receptor in human beings, which improves glucose tolerance and induces weight loss, mimicking the effects of endogenous oxyntomodulin. In addition to the effects of GLP-1 receptor agonists on promoting insulin secretion, lowering blood glucose and reducing body weight, mazdutide may also increase energy expenditure and improve hepatic fat metabolism through the activation of glucagon receptor.