Innovent Biologics has announced that the results of a phase 1b study of mazdutide (IBI362), a glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, in Chinese participants with overweight or obesity have shown a the mean reduction (percent reduction) from baseline in body weight was 9.23 kg (11.7%) for participants receiving mazdutide in the 9mg cohort.
"Higher-dose mazdutide showed favourable tolerability and safety profiles, as well as rapid and robust body weight loss efficacy, and has the potential to provide patients with severe obesity with treatment options comparable to the efficacy of bariatric surgery,” said principal investigator of this study, Professor Linong Ji from Peking University People's Hospital. “Combined with the results of phase I and phase II studies of lower-dose mazdutide, mazdutide has the potential to become one of the most powerful innovative anti-obesity drugs worldwide. I am very hopeful that mazdutide will achieve a great success in the phase III clinical studies and demonstrate benefit to patients as soon as possible.”
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 is estimated to improve glucose tolerance and induce 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.
This randomised, placebo-controlled multiple-ascending-dose study evaluated the safety, tolerability and pharmacokinetics/pharmacodynamics characteristics of mazdutide in Chinese participants with overweight or obesity. The results of lower-dose (3mg, 4.5mg and 6.0mg) cohorts have been published in eClinicalMedicine in August 2021. In higher-dose cohorts, 12 participants in each cohort were randomised 2:1 to receive subcutaneous 2.5-5.0-7.5-10.0 mg (10mg cohort) or 3.0-6.0-9.0mg (9mg cohort) mazdutide or placebo once weekly, with each dose level administered for four weeks.
In higher-dose cohorts, mazdutide up-titrated to 10mg and 9mg were both well tolerated. No participant discontinued the study due to adverse events. No serious adverse event or severe adverse event was reported. The most-commonly-reported treatment-emergent adverse events were gastrointestinal adverse events, mostly mild in severity.
At week 16, the mean reduction (percent reduction) from baseline in body weight was 7.62 kg (9.5%) for participants receiving mazdutide in the 10mg cohort. At week 12, the mean reduction (percent reduction) from baseline in body weight was 9.23kg (11.7%) for participants receiving mazdutide in the 9mg cohort. Improvements in BMI, waist circumference, blood pressure, lipid and serum uric acid were similar with those observed in the low-dose cohorts.
Multiple clinical studies of mazdutide are ongoing, including 1) the higher-dose cohort of a Phase II study of mazdutide in Chinese adults with obesity, with first participant dosing completed in September 2022 and 2) a Phase III clinical study in Chinese adults with overweight or obesity initiated, which received IND approval in October 2022.
"The publication of the Phase I results of mazdutide 9mg and 10mg cohorts further reflects the efficiency and translational collaboration between Chinese biopharmaceuticals and academia in early-stage clinical development of innovative metabolic drugs,” added Dr Lei Qian, Vice President of Clinical Development at Innovent. “The results of the higher-dose mazdutide make it the first single-agent anti-obesity drug worldwide to achieve a 12-week body weight loss by more than 11.5%. We are expecting more encouraging results in the ongoing phase II clinical study of mazdutide 9mg, which will lay a solid foundation for its potential as an alternative therapy of bariatric surgery. Mazdutide phase III studies are in progress and we hope that it may provide brand-new treatment options for Chinese patients who are overweight or obese in the near future."
Innovent entered into a licensing agreement with Eli Lilly and Company (Lilly) for the development and potential commercialisation of OXM3 (also known as Mazdutide, IBI362 or LY3305677), a dual GLP-1 and glucagon receptor agonist, in China. In parallel, Lilly is developing OXM3 outside China.