Head-to-head Superiority over Dulaglutide: Innovent's Phase 3 Clinical Trial DREAMS-2 of Mazdutide in Chinese Patients with Type 2 Diabetes were Orally Presented at EASD 2024

Rhea-AI Summary

Innovent Biologics (HKEX: 01801) presented Phase 3 clinical trial results for mazdutide, a GLP-1R and GCGR dual agonist, at the 60th Annual Meeting of EASD. The DREAMS-2 study demonstrated mazdutide's superiority over dulaglutide in both glycemic control and body weight reduction in Chinese patients with type 2 diabetes. After 28 weeks, mazdutide 4 mg and 6 mg showed mean HbA1c reductions of 1.69% and 1.73% respectively, compared to 1.36% for dulaglutide 1.5 mg. Weight reductions were 9.24% and 7.13% for mazdutide 4 mg and 6 mg, significantly outperforming dulaglutide (2.86%). Mazdutide also improved cardiometabolic risk factors and showed a favorable safety profile. The drug is currently under regulatory review in China for chronic weight management and type 2 diabetes treatment.

Positive

• Mazdutide demonstrated superiority over dulaglutide in glycemic control and weight reduction
• Mean HbA1c reductions of 1.69% and 1.73% for mazdutide 4 mg and 6 mg vs 1.36% for dulaglutide
• Weight reductions of 9.24% and 7.13% for mazdutide 4 mg and 6 mg vs 2.86% for dulaglutide
• Improvements in multiple cardiometabolic risk factors
• Favorable safety and tolerability profile with no new safety signals
• Two NDAs under review by NMPA in China for weight management and type 2 diabetes

Negative

• None.

SAN FRANCISCO and SUZHOU, China, Sept. 11, 2024 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, announces that the Phase 3 clinical trial results for mazdutide, a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese adults with type 2 diabetes (T2D) (DREAMS-2) were presented as a late-breaking oral presentation (Abstract #: LBA 16) at the 60th Annual Meeting of the European Association for the Study of Diabetes^® (EASD). The study results demonstrated the superiority of mazdutide to dulaglutide in both glycemic control and body weight reduction in Chinese participants with T2D. Additionally, mazdutide treatment improved several cardiometabolic risk factors, including blood pressure, lipids, serum uric acid and liver enzymes. Detailed results will be published in peer-reviewed journals.

Meanwhile, the first Phase 3 study results of mazdutide in the weight loss of overweight/obese subjects (GLORY-1) were reported in oral presentation session of EASD. Mazdutide also works as a breakthrough weight-loss drug that offers dual-targeted fat burning, liver function improvement, and long-lasting weight reduction, providing comprehensive metabolic benefits to support weight loss and promote a healthier life.

DREAMS-2 (ClinicalTrials.gov, NCT05606913) enrolled 731 Chinese participants with T2D (mean age 51.8 years, mean baseline HbA1c 8.22%, mean baseline body weight 76.95 kg), whose diabetes was inadequately controlled with metformin alone or in combination with other oral anti-diabetic medications. Participants were randomized to receive mazdutide 4 mg, mazdutide 6 mg or dulaglutide 1.5 mg for 28 weeks. The primary endpoint was the change in HbA1c from baseline to week 28.

Superiority of mazdutide to dulaglutide in glycemic control^*

For the efficacy estimand, after 28 weeks of treatment, mean reductions in HbA1c from baseline were 1.69% and 1.73% for mazdutide 4 mg and mazdutide 6 mg, respectively, demonstrating superiority over dulaglutide 1.5 mg (1.36%). At week 28, 71.2% and 74.2% of participants receiving mazdutide 4 mg and 6 mg, respectively, achieved HbA1c <7.0% compared to 62.1% with dulaglutide. Additionally, 54.8% and 63.1% of participants receiving mazdutide 4 mg and 6 mg, respectively, achieved HbA1c ≤6.5% , compared to 42.1% for dulaglutide.

Mazdutide's superiority over dulaglutide in weight loss and HbA1c/weight composite endpoints*

After 28 weeks of treatment, participants treated with mazdutide 4 mg and mazdutide 6 mg experienced mean weight reductions of 9.24% and 7.13%, respectively, significantly outperforming dulaglutide (2.86%). At week 28, 62.4% and 78.2% of participants receiving mazdutide 4 mg and mazdutide 6 mg achieved a weight reduction of ≥5%, compared to 26.9% for dulaglutide. Additionally, 50.1% and 64.3% of participants with mazdutide 4 mg and mazdutide 6 mg achieved both a weight reduction of ≥5% and HbA1c < 7.0%, respectively (dulaglutide 19.4%).

Improvements on multiple cardiometabolic risk factors by mazdutide

Mazdutide treatment also led to significant and clinically meaningful improvements on  fasting glucose, post-prandial glucose, waist circumference, blood pressure, lipids, serum uric acid and transaminases, mostly greater than dulaglutide. Detailed results will be published in peer-reviewed journals.

Favorable safety and tolerability profile and no new safety signals

• Mazdutide was well tolerated, with low incidence of TEAEs leading to treatment discontinuation.
• The overall safety profile was consistent with previous clinical studies of mazdutide, with no new safety signals observed. Gastrointestinal symptoms were the most common adverse events, mostly mild to moderate in severity, transient, and occurring mainly during dose escalation. No severe hypoglycemia was reported with mazdutide, and the incidence of grade 1-2 hypoglycemia was comparable to dulaglutide.

Mazdutide is the first GLP-1R/GCGR dual agonist in the regulatory review status, with a first new drug application (NDA) for chronic weight management and a second NDA for T2D currently under review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China.

Professor Lixin Guo, the principal investigator of the clinical study, Department of Endocrinology in Beijing Hospital, said: "The incidence of type 2 diabetes in China remains high, and a considerable proportion of patients have overweight/obesity, cardiovascular and kidney diseases. In recent years, GLP-1 receptor agonists have offered improved treatment options for patients with type 2 diabetes, providing comprehensive benefits in glucose control, weight management, and cardiovascular and kidney health. As a result, GLP-1-based therapies have become a hot spot and frontier in the development of drugs for metabolic diseases. Mazdutide, one of the fastest-advancing GLP-1R and GCGR dual agonists in clinical development globally, has demonstrated superiority in glucose-lowering and weight-reducing efficacy over dulaglutide in a Phase 3 study of patients with type 2 diabetes. With its additional metabolic benefits and favorable safety profile, mazdutide represents a new generation of GLP-1 therapies for the treatment of type 2 diabetes. I look forward to the clinical availability of mazdutide as soon as possible to provide new treatment options for patients with type 2 diabetes."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, said: "China has a large population of people with diabetes, and the task of prevention and treatment is arduous. There is an urgent need for more effective, safer and more convenient innovative drugs. The Phase 3 study results of mazdutide versus dulaglutide reported at EASD were very successful. They showed comprehensive benefits of mazdutide in blood glucose control, weight loss and multiple metabolic indicators. Combined with the results of DREAMS-1, another Phase 3 study of mazdutide as monotherapy in patients with type 2 diabetes, Innovent has submitted an application for the marketing approval of mazdutide for the treatment of type 2 diabetes to the regulatory agency. We look forward to the approval of mazdutide and its potential to benefit a large number of type 2 diabetes patients seeking improvements in glycemic control, weight management and cardiovascular metabolic indicators."

About Diabetes

According to the 2021 global diabetes overview by the International Diabetes Federation, China leads the world in the number of patients with diabetes, with an estimated 140 million cases in 2021 and projected to reach 174 million by 2045^[1]. Poor glycemic control can lead to irreversible microvascular and macrovascular complications, including reduced visual acuity, blindness, renal dysfunction, peripheral neuropathy, myocardial infarction, stroke and amputation^[2]. The high prevalence of diabetes and its serious complications pose a significant threat to human health. Currently, various therapeutic approaches are available for diabetes management. In addition to controlling blood glucose, new hypoglycemic drugs are being developed to offer additional benefits such as weight loss, cardiovascular risk reduction and kidney protection^[3].

About Mazdutide (IBI362)

Innovent entered into an exclusive license 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. As a mammalian oxyntomodulin (OXM) analogue, mazdutide promotes insulin secretion, lowers blood glucose and reduces body weight similar to GLP-1 receptor agonists. Additionally, it may increase energy expenditure and improve hepatic fat metabolism by activating the glucagon receptor. Mazdutide has strong efficacy in weight loss and lowering glucose levels in clinical studies. It also offers multiple cardio-metabolic benefits, such as reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, and liver fat content, while improving insulin sensitivity.

Mazdutide has two NDAs accepted by China's NMPA for review, including:

• For the chronic weight management in adults with obesity or overweight;
• For the glycemic control in adults with type 2 diabetes.

Currently, a total of five Phase 3 studies of mazdutide are underway, including:

• Phase 3 study conducted in Chinese adults with overweight or obesity (GLORY-1);
• Phase 3 study conducted in Chinese adults with moderate to severe obesity (GLORY-2);
• Phase 3 study in newly treated Chinese patients with type 2 diabetes (DREAMS-1);
• Phase 3 study comparing mazdutide and dulaglutide in Chinese patients with type 2 diabetes (DREAMS-2);
• Phase 3 study comparing mazdutide and semaglutide in Chinese patients with type 2 diabetes and obesity (DREAMS-3).

Among them, GLORY-1, DREAMS-1 and DREAMS-2 have reached the study endpoints. 

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 11 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).

Forward-looking statement

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect.

References:

[1].  Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projects for 2045 [published correction appeals in Diabetes Res Clin Pract. 2023 Oct; 204: 110945]. Diabetes Res Clin Pract. 2022; 183: 109119. doi: 10.1016/j.diabres.2021. 109119 [2].  Gregg EW, Sattar N, Ali MK. The changing face of diabetes complications. Lancet Diabetes Endocrinol. Published online 2016. doi: 10.1016/S2213-8587 (16) 30010-9 [3].  Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes-state-of-the-art. Mol Metab. Published online 2020. doi: 10.1016/j.molmet.2020. 101102 * Note: The results of treatment-policy estimand and those of efficacy estimand are consistent.

 

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SOURCE Innovent Biologics

FAQ

What were the key results of the DREAMS-2 Phase 3 trial for mazdutide (IVBIY)?

The DREAMS-2 Phase 3 trial showed that mazdutide was superior to dulaglutide in both glycemic control and weight reduction in Chinese patients with type 2 diabetes. Mazdutide 4 mg and 6 mg achieved HbA1c reductions of 1.69% and 1.73%, compared to 1.36% for dulaglutide 1.5 mg. Weight reductions were 9.24% and 7.13% for mazdutide 4 mg and 6 mg, versus 2.86% for dulaglutide.

How did mazdutide (IVBIY) perform in terms of safety in the DREAMS-2 trial?

Mazdutide demonstrated a favorable safety and tolerability profile in the DREAMS-2 trial. The most common adverse events were gastrointestinal symptoms, mostly mild to moderate and transient. No severe hypoglycemia was reported, and the incidence of grade 1-2 hypoglycemia was comparable to dulaglutide. No new safety signals were observed.

What is the current regulatory status of mazdutide (IVBIY) in China?

Mazdutide currently has two New Drug Applications (NDAs) under review by the National Medical Products Administration (NMPA) in China. One NDA is for chronic weight management, and the other is for the treatment of type 2 diabetes.

How does mazdutide (IVBIY) affect cardiometabolic risk factors?

The DREAMS-2 trial showed that mazdutide treatment led to significant improvements in multiple cardiometabolic risk factors. These included improvements in fasting glucose, post-prandial glucose, waist circumference, blood pressure, lipids, serum uric acid, and liver enzymes, with most improvements being greater than those seen with dulaglutide.