Innovent Biologics’ Phase 3 clinical trial (DREAMS-2) of mazdutide (IBI362) in Chinese subjects with type 2 diabetes (T2D) has met its primary endpoint. The study results suggested that mazdutide was superior compared with dulaglutide for glycaemic control, and mazdutide also showed multiple cardiometabolic benefits in T2D patients including weight loss, blood lipid, blood pressure, serum uric acid, liver enzymes, etc.
DREAMS-2 is a multi-centre, randomised Phase 3 clinical study to compare the efficacy and safety of mazdutide and dulaglutide in Chinese subjects with T2D who have inadequate glycaemic control with metformin monotherapy or combination therapy of metformin with other oral drugs. The study enrolled 731 subjects to receive either mazdutide 4.0mg, mazdutide 6.0mg or dulaglutide 1.5 mg for 28 weeks. The primary endpoint was the change from baseline to week 28 in glycated haemoglobin (HbA1c) levels. The study used a non-inferiority design, and further superiority testing was performed after non-inferiority was achieved.
After 28 weeks of treatment, mazdutide 4.0mg and mazdutide 6.0mg showed non-inferiority to dulaglutide 1.5mg in terms of improvement in HbA1c level from baseline. Based on these results, the superiority test was further performed, and both mazdutide 4.0mg and 6.0mg achieved superiority to dulaglutide 1.5mg.
Statistical superiority was achieved in the following endpoints in both mazdutide 4.0mg and mazdutide 6.0mg groups after 28 weeks of treatment, including the change from baseline in HbA1c (superiority), percent change from baseline in body weight, proportion of subjects with HbA1c <7.0% and weight loss of ≥5%, and proportion of subjects with HbA1c <7.0%*.
"In China, T2D patients often have a variety of chronic diseases as comorbidities, such as obesity, hyperlipidaemia, coronary heart disease, hypertension and so on. Therefore, the management of T2D should take into consideration the improvements in blood glucose, blood lipid, blood pressure and other aspects,” said Professor Lixin Guo, the principal investigator of the clinical study, Department of Endocrinology in Beijing Hospital. “In endocrine and CVM areas, GLP-1-based drugs are the hotspot of research and development for the healthcare industry as well as for clinicians, especially multi-target drugs that are potentially more efficacious and can provide more metabolic benefits. DREAMS-2 is the first Phase 3 clinical study head-to-head with dulaglutide in China, which has high clinical significance and academic value. The results of this study showed that mazdutide, compared with dulaglutide, has a stronger glycaemic lowering effect and favourable safety profile. More importantly, mazdutide provided more comprehensive benefits in weight loss, blood lipid, blood pressure, blood uric acid, liver enzymes and other aspects. I look forward to the NDA submission of mazdutide in T2D and wish it to benefit hundreds of millions of diabetic patients in China."
Mazdutide showed comprehensive benefits beyond glucose-lowering and weight loss in multiple cardiometabolic indicators (blood pressure, blood lipids, serum uric acid and liver enzymes). Mazdutide also showed significant advantages compared with dulaglutide in various indicators, including the proportion of subjects with HbA1c ≤ 6.5%, changes in fasting blood glucose and seven-point fingerstick blood glucose from baseline, the proportion of subjects with body weight loss of ≥ 5% and ≥ 10%, absolute change in body weight from baseline, waist circumference, body mass index (BMI), systolic blood pressure (SBP), triglyceride (TG), serum uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), etc.
Gastrointestinal adverse reactions were the most common adverse events, most were mild to moderate in severity, transient and mainly occurred during the first 12-week titration period.
No severe hypoglycaemia occurred; the incidence of moderate or severe hypoglycaemia was comparable to that of dulaglutide; and the incidence of hypoglycaemia was lower in indirect comparison to reported in registrational studies of other GLP-1 drugs.
The overall safety profile was consistent with that observed in previous clinical studies of mazdutide and no new safety signals observed.
"China has the largest number of T2D patients in the world, and the prevalence of T2D among adults in China has reached 11.9%. Together with other investigators of the DREAMS-2 study, I am pleased to see that mazdutide, as a new generation of GLP-1R/GCGR dual target agonist, has met the primary endpoint and demonstrated superiority in change from baseline in HbA1c and multiple metabolic benefits compared with dulaglutide,” added Professor Yang Wenying, the principal investigator of the clinical study, Department of Endocrinology in China Japan Friendship Hospital. “DREAMS-2 is a landmark study as it is the first successful registrational study of a GLP-1R/GCGR dual target agonist in T2D. I believe that in the near future, mazdutide will provide a new and better choice for the treatment of type 2 diabetes in China."
Mazdutide is a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, the first GLP-1R/GCGR dual agonist in the regulatory review status, with the first new drug application (NDA) for chronic weight management under review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). DREAMS-2, as one of the registrational clinical studies of mazdutide, will provide high-quality evidence of mazdutide for Chinese population with T2D. Innovent plans to read out the results of another DREAMS-1 Phase 3 clinical study in mid-2024 and submit to the CDE an NDA for the treatment of T2D with mazdutide. Detailed data from the DREAMS-1 and DREAMS-2 studies will be further analysed and published at academic congresses or in clinical journals.
"There is a huge population of diabetes in China. Innovative drugs that are more effective, safer and more convenient are urgently needed. In the DREAMS-2 study, mazdutide showed comprehensive superiority to dulaglutide, one of the most-described glucose-lowering drugs in the world,” said Dr Lei Qian, Vice President of Clinical Development of Innovent. “We will further analyse the study data and strive to submit an NDA for T2D as soon as possible this year, so as to help more Chinese T2D patients to achieve target blood glucose levels and acquire metabolic benefits. At the same time, we look forward to the performance of mazdutide in the DREAMS-3 study, a head-to-head study with semaglutide."