Innovent Biologics, a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, announces that the 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 adults with type 2 diabetes (T2D) met the primary endpoint and all key secondary endpoints. Another Phase 3 clinical trial DREAMS-2 has previously met the study endpoints, in which mazdutide showed superiority compared with dulaglutide for glycaemic control, as well as weight loss and multiple cardiometabolic benefits in T2D patients. Innovent plans to submit a new drug application (NDA) of mazdutide for T2D treatment to the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) in the near term, following the acceptance of its first NDA for chronic weight management in February 2024.

DREAMS-1 (NCT05628311) is a randomized, double-blind, placebo-controlled, Phase 3 clinical trial designed to evaluate the efficacy and safety of mazdutide in Chinese adults with T2D and insufficient glycemic control using diet and exercise alone. A total of 320 participants were enrolled in the study (mean HbA1c and body weight at baseline were 8.24% and 77.7 kg, respectively) and randomized in a 1: 1: 1 ratio to receive either mazdutide 4 mg, mazdutide 6 mg or placebo for 24 weeks in the double-blind period; after completing the double-blind treatment period, participants in the 4 mg and 6 mg groups maintained receiving treatment, while those in the placebo group were switched to receive mazdutide 6 mg for 24 weeks. The primary endpoint was the change from baseline in glycated hemoglobin (HbA1c) at week 24; a superiority design was used to test the superiority of each dose group of mazdutide versus placebo for the primary endpoint and key secondary endpoints.

The primary endpoint was successfully met, showing a robust glucose-lowering efficacy of mazdutide

At week 24, the reduction from baseline in HbA1c in both the mazdutide 4 mg (1.57%) and 6 mg groups (2.15%) was superior to the placebo (0.14%; both p-values < 0.0001). The efficacy of HbA1c reduction in patients treated with mazdutide was sustained through week 48.

Key secondary endpoints suggest dual advantages of mazdutide in glucose-lowering and weight-reduction

• At week 24, mazdutide showed significantly higher weight reduction compared with placebo. The proportion of patients who achieved HbA1c<7.0%, weight reduction≥5%, and dual targets of HbA1c<7% and weight reduction≥5% were significantly higher in mazdutide groups than placebo. At week 48, patients treated with mazdutide 6mg showed weight loss of 9.6% from baseline.

Mazdutide brought multiple benefits for patients with T2D

Besides HbA1c and weight loss, mazdutide also reduced cardiovascular metabolic indicators including postprandial blood glucose, waist circumference, blood pressure, blood lipids, transaminases, and urinary albumin-to-creatinine ratio.

Favorable safety and tolerability profile with no additional safety signals

• Overall safety and tolerability were favorable and consistent with previous clinical studies of mazdutide. The most commonly reported adverse events were gastrointestinal adverse events, mostly mild to moderate. No new safety signals were identified.
• The incidence of hypoglycemia events was low, most of which were Grade 1 hypoglycemia (3.0 mmol/L ≤ blood glucose < 3.9 mmol/L). No severe hypoglycemia events were reported.

Professor Dalong Zhu, the leading principal investigator of the study, Affiliated Drum Tower Hospital, Medical School of NanjingUniversity, stated, "Patients with T2D often have multiple chronic conditions, including obesity, hyperlipidemia, coronary heart disease, hypertension, etc. Effective disease management should encompass the control of blood glucose, blood lipid, blood pressure and other aspects. The multifaceted benefits of multi-target GLP-1 drugs have garnered significant interest from both the research and clinical communities. As a novel GLP-1R/GCGR dual-target agonist, mazdutide not only demonstrated significant glucose-lowering effects in DREAMS-1 study, but also provided a range of comprehensive benefits including reduction in body weight, blood lipids, blood pressure, liver enzymes, etc., while maintaining favorable safety and tolerability. I hope that mazdutide will be marketed as soon as possible to help Chinese T2D patients achieve target blood glucose levels multiple metabolic benefits."

Professor Jiajun Zhao, the leading principal investigator of the study, Shandong Provincial Hospital, stated, "China has the highest prevalence of diabetes globally with more than 140 million people living with diabetes. The number continues to rise annually, presenting a challenge in disease prevention and management. There is an urgent need for innovative medications that offer enhanced efficacy and comprehensive benefits. In the treatment of Chinese patients with T2D, mazdutide showed excellent glucose-lowering effects and multiple metabolic benefits. Under long-term treatment, its efficacy, safety and tolerability remained consistently stable. The results of DREAMS-1 provide significant medical evidence supporting the use of next-generation multi-target GLP-1R/GCGR drugs for treating T2D. I believe mazdutide will offer a superior therapeutic option for Chinese patients with T2D in future."

Dr Lei Qian, Vice President of Clinical Development of Innovent, stated,  "Mazdutide is the first and fastest-developed GLP-1R/GCGR dual agonist in the world, and we are actively promoting the development of mazdutide for weight loss, T2D and other indications. The results of DREAMS-1 provided high-quality, compelling evidence for T2D treatment in China, particularly in previously untreated patients whose blood glucose was inadequately controlled with diet and exercise alone. The results of another Phase 3 study DREAMS-2, involving patients with T2D inadequately controlled by oral antidiabetic drugs (OADs), met the study endpoints in May 2024. Together, the two studies demonstrate mazdutide's comprehensive efficacy in improving glycemic control, promoting weight loss, and enhancing metabolic outcomes in patients with T2D. Detailed data will be published at academic congresses or academic journals. Meanwhile, we look forward to the performance of mazdutide in the DREAMS-3 study, a head-to-head study with semaglutide."