Second phase III trial of mazdutide in Chinese patients with type 2 diabetes met study endpoints, and Innovent Biologics plans to submit NDA of mazdutide to the NMPA.

Another Phase III 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 III 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 less than 7.0%, weight reduction greater than 5%, and dual targets of HbA1c less than 7% and weight reduction greater than 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 less than 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 Nanjing University, 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.