Innovent Biologics has announced that the first participant has been successfully dosed in the higher-dose cohort of a phase 2 clinical trial of mazdutid, a glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese adults with obesity. This randomised, double-blinded, placebo-controlled is designed to evaluate the efficacy and safety of mazdutide in Chinese participants with overweight or obesity.
Results for the low dose cohorts (3.0mg, 4.5mg and 6.0mg) were disclosed in June 2022 and the primary endpoint was met. At Week 24, each dose of mazdutide showed significant efficacy on body weight loss vs. placebo in a dose-dependent manner and brought multiple cardio-metabolic benefits to participants; meanwhile, mazdutide was well tolerated and the overall safety profile was similar to other drugs of the same class.
In addition, mazdutide titrated to 9mg showed a good safety profile and a 12-week body weight loss of 11.7% in the phase 1b study. Based on these results, Innovent will further evaluate the efficacy and safety for a higher dose (9.0mg) mazdutide in Chinese patients with obesity. A total of 80 participants are planned to be enrolled and will be randomized in a 3:1 ratio to receive mazdutide 9.0mg or placebo for 24 weeks. The primary endpoint was the percent change from baseline in body weight at Week 24.
"Obesity is associated with a variety of chronic non-communicable diseases and is listed as one of the important risk factors affecting the disease burden. The prevalence and growth rate of obesity in China rank first in the world, and drugs that can achieve effective and safe weight loss are therefore urgently needed in the clinic. Clinical studies of mazdutide in overweight or obese population have demonstrated significant efficacy on body weight loss and comprehensive metabolic improvement,” explained Professor Linong Ji, the principal investigator of the study, Peking University People's Hospital. “Treatment of mazdutide 6.0mg for six months resulted in 11.6% body weight loss in participants in the low-dose cohorts of the phase 2 study, demonstrating its best-in-class potential. I am confident that a 9.0mg dose of mazdutide will show even more satisfactory efficacy on body weight loss and will offer a new treatment option for participant with moderate to severe obesity."
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), which uses a fatty acid side chain to prolong the duration of action and allow once-weekly administration. Mazdutide is thought to exert its biological effects by activating 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. The treatment of metabolic diseases by activating multiple metabolism-related targets simultaneously is currently the worldwide trend in drug development.
“In the Phase 2 study in Chinese participants with overweight or obesity, low-dose mazdutide showed robust efficacy on body weight loss and multiple improvement in metabolic parameters, reflecting the Best-in-Class potential of mazdutide among GLP-1 receptor agonists and co-agonists,” added Dr Lei Qian, Vice President of Clinical Development at Innovent. "To further extend its clinical utility, we will continue to explore the clinical benefit of mazdutide 9.0mg in adults with obesity. The result of the phase 1 study suggests that mazdutide is the first single-agent anti-obesity molecule, among all approved or under development, that achieves a 12-week body weight loss by more than 11.5%. We hope that the higher-dose mazdutide will provide a safer, bariatric surgery-like and more accessible treatment option to patients with obesity."