Innovent Biologics has revealed its phase 2 clinical study of higher dose (9mg) mazdutide in Chinese adults with obesity achieved the 24-week primary endpoint. The company entered into a licensing agreement with Eli Lilly and Company (Lilly) for the development and potential commercialisation of OXM3 (also known as mazdutide), a GLP-1R and GCGR dual agonist, in China. As a mammalian oxyntomodulin (OXM) analogue, 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.
“I am pleased to see the weight loss efficacy of mazdutide 9 mg has been further improved versus mazdutide 6mg while showing good tolerability and safety. The observed efficacy of mazdutide 9mg after 24 weeks of treatment is approaching that of metabolic surgery, which suggests the potential of mazdutide to become a more ideal therapeutic drug for patients with moderate to severe obesity,” said Professor Linong Ji, the leading principal investigator of the study, Peking University People's Hospital. “This study also fills the gap in the clinical research of drug treatment of patients with severe obesity in Chinese and even East Asian populations. I am hopeful that mazdutide 9 mg will also show satisfactory results in future phase 3 studies."
The randomised, double-blind, placebo-controlled phase 2 clinical study to evaluate the efficacy and safety of mazdutide 9mg in Chinese subjects with obesity [body mass index (BMI) ≥30.0 kg/m2]. A total of 80 subjects were enrolled (mean baseline weight 96.9 kg, mean height 168.0 cm, mean BMI 34.3 kg/m2) and randomised in a 3:1 ratio to mazdutide 9mg group or placebo group to receive treatment once a week for 24 weeks. The primary endpoint is the percent change in body weight from baseline versus placebo after 24 weeks of treatment. The study will also extend treatment to 48 weeks.
The results showed that mazdutide 9mg demonstrated superior body weight loss versus placebo in Chinese subjects with obesity. After 24 weeks of treatment, the treatment difference of the mean percent change in body weight from baseline versus placebo was -15.4% (p<0.0001; the treatment difference of the mean change in body weight from baseline versus placebo was -14.7 kg,p<0.0001). Meanwhile, 81.7%,65.0%,31.7% and 21.7% of the subjects in the mazdutide 9mg group achieved 5% or more, 10% or more, 15% or more and 20% or more weight loss from baseline, respectively, while no subject in the placebo group lost 5% or more of body weight from baseline.
In terms of safety, the overall tolerability and safety of the mazdutide 9 mg was favourable. The drop-out rate of the mazdutide group was lower than that of the placebo group. No subject in the mazdutide group discontinued treatment due to adverse events. No serious adverse events occurred. Except for COVID-19 infection, the most commonly-reported adverse events were gastrointestinal-related adverse events, most of which were mild or moderate and transient.
The study is still in progress, and the data of other secondary and exploratory endpoints of the study will be analyzed and disclosed after the end of the study.
"The overweight and obese population in China has continued to increase in recent years. There are about 160 million obese people across China (BMI ≥ 28.0 kg/m2), of which approximately 10 million are with moderate and severe obesity (BMI ≥ 32.5 kg/m2). The risk of cardiovascular and cerebrovascular diseases for these patients is extremely high, and the quality of daily life and mental health of these patients are significantly affected,” added Ji. “Compared with the general obese population, moderately- to severely- obese patients urgently need effective and safe weight loss options. At present, metabolic surgery is the main treatment for people with a BMI ≥ 32.5 kg/m2, other treatment options are limited. Despite the obvious efficacy of surgical weight loss, it is only used in a small number of patients for many reasons. In recent years, the development of GLP-1 receptor agonists, especially a new generation of dual-target agonists, has brought prospects for weight loss drugs. However, there are few clinical studies on GLP-1 receptor agonists in patients with moderate to severe obesity in the world, especially in the Chinese population.”
There are currently three key phase 3 studies of mazdutide 4mg and 6mg in Chinese patients with overweight or obesity (GLORY-1) and type 2 diabetic (DREAM-1 and DREAM-2) underway. The Phase 2 clinical study of mazdutide 9 mg in Chinese patients with obesity is in progress.