Innovent, Lilly's mazdutide outdoes Novo's semaglutide in phase 3 trial

Innovent Biologics' dual GLP-1/glucagon receptor agonist, mazdutide, outperformed Novo Nordisk's semaglutide in a late-stage, head-to-head clinical trial among overweight individuals with type 2 diabetes, the company said.

In the phase 3 DREAMS-3 study, mazdutide was more effective than semaglutide in achieving the primary endpoint, with 48% of participants achieving both HbA1c < 7.0% and ≥10% weight loss at week 32, compared to 21% for semaglutide (p < 0.0001).

Participants treated with mazdutide saw mean HbA1c levels fall by 2.03% from baseline, while those in the semaglutide group experienced a 1.84% drop.

Patients in the mazdutide arm also lost an average of 10.29% of their body weight, outperforming semaglutide, which only averaged 6%.

Mazdutide was developed by Novo's direct competitor, Eli Lilly, but in 2019, Innovent Biologics acquired the rights to develop, manufacture and commercialize mazdutide in China.

Following a string of successful phase 3 trials, China's National Medical Products Administration approved mazdutide (LY3305677), branded as Xinermei, in June, making it the world's first dual GLP-1/glucagon receptor agonist approved for weight loss.

Under the agreement with Innovent, Lilly retains ownership of the active ingredient and its commercialization rights outside of China.

The company is currently running a phase 2 master protocol study (NCT06143956) of mazdutide in a largely US-based population of overweight and obese adults, alongside other Eli Lilly obesity drugs.

However, Lilly's triple-agonist candidate, retatrutide (LY3437943), which targets GLP-1, GIP and glucagon receptors, is further along in development.

Currently, retatrutide is being tested in multiple phase 3 trials for weight loss, diabetes, sleep apnea, osteoarthritis and chronic back pain and to reduce cardiovascular and kidney risks linked to obesity.

Innovent's trial data comes just weeks after Eli Lilly announced positive topline results from its phase 3 ACHIEVE-2 and ACHIEVE-5 trials of orforglipron, its oral GLP-1 receptor agonist for treating type 2 diabetes.

Meanwhile, Novo is looking to reclaim its competitive edge in the GLP-1 market.

In May, the FDA accepted the company's new drug application for an oral version of Wegovy, which could become the first oral GLP-1 therapy approved for chronic weight management in adults with obesity or who are overweight with one or more comorbidities.

Novo is also hoping to expand treatment options for people living with obesity and type 2 diabetes with its investigational drug, CagriSema. CagriSema combines semaglutide and cagrilintide -- a dual amylin and calcitonin receptor agonist.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.