First participant dosed GLORY-OSA trial of mazdutide in China

The first participant has been successfully dosed in a Phase 3 clinical trial (GLORY-OSA) of mazdutide, a dual glucagon (GCG) and glucagon-like peptide-1 (GLP-1) receptor agonist, in Chinese participants with moderate-to-severe obstructive sleep apnoea (OSA) and obesity (BMI ≥ 28 kg/m2). This is the seventh Phase 3 clinical study of mazdutide in China, continuing to explore its potential in managing obesity and a range of metabolic syndromes, with the aim of generating more comprehensive and high-quality evidence to support clinical application.

GLORY-OSA is a multicentre, randomised, open-label Phase 3 clinical study (NCT06931028) comparing the efficacy and safety of mazdutide 9mg versus placebo in Chinese participants. The primary endpoint is the change in apnoea-hypopnea index (AHI) from baseline to Week 48.

Globally, an estimated 425 million people aged 30 to 69 live with moderate-to-severe OSA, with China bearing the highest burden at approximately 66 million cases. However, the diagnosis rates remain critically low, with less than 1% in China and only 20% in the US. The condition disproportionately affects individuals living with obesity, with a prevalence of 40%, increasing to 80.5% among those undergoing bariatric surgery. OSA-associated co-morbidities, including hypertension, cardiac arrhythmias, stroke, and metabolic syndrome, are strongly correlated with OSA severity.

Positive airway pressure (PAP) is the first-line treatment for OSA, and certain patients experience transformative benefits from PAP. Challenges exist, however, as many others are unable to accept or adhere to PAP treatment due to the burdensome nature of the therapy. Moreover, current evidence does not strongly support a direct link between PAP and improved cardiometabolic outcomes (eg mortality, hypertension, myocardial infarction, stroke).

Recently, the FDA approved Zepbound (tirzepatide), a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist, as the first and only prescription medicine for moderate-to-severe OSA in adults with obesity. There is currently no approved treatment for OSA in China, highlighting a significant unmet medical need. The literature suggests  that a 10% reduction in weight is associated with a 26% decrease in AHI, and that each 1-unit reduction in BMI corresponds to a 2-3 unit decrease in AHI. As such, weight loss medications have emerged as potential treatments for OSA.

"Patients with untreated OSA face significantly increased risks of cardiovascular diseases, metabolic disorders, neurocognitive decline, and traffic accidents. Their quality of life and labour capacity are often severely hampered. The OSA proportion of patients living with obesity is large and grows year after year. Despite this, an effective drug treatment regimen for OSA is lacking in China,” explained Professor Tianpei Hong, the Principal Investigator of the Study, Peking University Third Hospital. “In our Phase 3 study GLORY-1, mazdutide showed good weight loss efficacy with multi-cardiovascular metabolism improvement, and a well-tolerated safety profile, which positions mazdutide as the world's first dual GCG/GLP-1 receptor targeted drug for patients with OSA and obesity. I will work closely with the GLORY-OSA research team to ensure the successful and high-quality completion of this study, with the ultimate goal of obtaining robust clinical evidence and expanding treatment options for Chinese patients with moderate-to-severe OSA and obesity."

Innovent entered into an exclusive license 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, mazdutide may offer additional benefits beyond those of GLP-1 receptor agonists - such as promoting insulin secretion, lowering blood glucose and reducing body weight - by also activating the glucagon receptor to increase energy expenditure and improve hepatic fat metabolism.