Innovent Announces the Second Phase 3 Trial of Mazdutide in Chinese Patients with Type 2 Diabetes Met Study Endpoints, and Plans to Submit NDA of Mazdutide to the NMPA

Rhea-AI Summary

Innovent Biologics (HKEX: 01801) announces that the Phase 3 clinical trial (DREAMS-1) of mazdutide, a GLP-1R and GCGR dual agonist, in Chinese adults with type 2 diabetes (T2D) met its primary endpoint and key secondary endpoints. The study showed superior glycemic control and weight loss compared to placebo. At week 24, HbA1c reduction in the mazdutide 4 mg (1.57%) and 6 mg (2.15%) groups was significantly better than placebo (0.14%). Mazdutide also demonstrated multiple cardiometabolic benefits and a favorable safety profile.

Innovent plans to submit a new drug application (NDA) for mazdutide to treat T2D to China's NMPA soon, following its first NDA for chronic weight management in February 2024. The DREAMS-1 results, along with the previously successful DREAMS-2 trial, provide strong evidence for mazdutide's efficacy in T2D treatment.

Positive

• Phase 3 trial (DREAMS-1) of mazdutide met primary and key secondary endpoints
• Mazdutide showed superior glycemic control with HbA1c reduction of 1.57% (4 mg) and 2.15% (6 mg) vs 0.14% for placebo at week 24
• Significant weight loss achieved, with 9.6% reduction from baseline at week 48 for 6 mg dose
• Multiple cardiometabolic benefits observed, including improvements in blood pressure, lipids, and liver enzymes
• Favorable safety and tolerability profile with no new safety signals identified
• Plans to submit NDA for T2D treatment to China's NMPA following acceptance of NDA for weight management

Negative

• None.

SAN FRANCISCO and SUZHOU, China, July 21, 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 (DREAMS-1) of mazdutide (Innovent R&D code: IBI362), a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese adults with type 2 diabetes (T2D) met the primary endpoint and all key secondary endpoints. Another Phase 3 clinical trial DREAMS-2 has previously met the study endpoints, in which mazdutide showed superiority compared with dulaglutide for glycaemic control, as well as weight loss and multiple cardiometabolic benefits in T2D patients. Innovent plans to submit a new drug application (NDA) of mazdutide for T2D treatment to the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) in the near term, following the acceptance of its first NDA for chronic weight management in February 2024.

DREAMS-1 (NCT05628311) is a randomized, double-blind, placebo-controlled, Phase 3 clinical trial designed to evaluate the efficacy and safety of mazdutide in Chinese adults with T2D and insufficient glycemic control using diet and exercise alone. A total of 320 participants were enrolled in the study (mean HbA1c and body weight at baseline were 8.24% and 77.7 kg, respectively) and randomized in a 1: 1: 1 ratio to receive either mazdutide 4 mg, mazdutide 6 mg or placebo for 24 weeks in the double-blind period; after completing the double-blind treatment period, participants in the 4 mg and 6 mg groups maintained receiving treatment, while those in the placebo group were switched to receive mazdutide 6 mg for 24 weeks. The primary endpoint was the change from baseline in glycated hemoglobin (HbA1c) at week 24; a superiority design was used to test the superiority of each dose group of mazdutide versus placebo for the primary endpoint and key secondary endpoints.

The primary endpoint was successfully met, showing a robust glucose-lowering efficacy of mazdutide

At week 24, the reduction from baseline in HbA1c in both the mazdutide 4 mg (1.57%) and 6 mg groups (2.15%) was superior to the placebo (0.14%; both p-values < 0.0001). The efficacy of HbA1c reduction in patients treated with mazdutide was sustained through week 48.

Key secondary endpoints suggest dual advantages of mazdutide in glucose-lowering and weight-reduction

• At week 24, mazdutide showed significantly higher weight reduction compared with placebo. The proportion of patients who achieved HbA1c<7.0%, weight reduction≥5%, and dual targets of HbA1c<7% and weight reduction≥5% were significantly higher in mazdutide groups than placebo. At week 48, patients treated with mazdutide 6mg showed weight loss of 9.6% from baseline.

Mazdutide brought multiple benefits for patients with T2D

Besides HbA1c and weight loss, mazdutide also reduced cardiovascular metabolic indicators including postprandial blood glucose, waist circumference, blood pressure, blood lipids, transaminases, and urinary albumin-to-creatinine ratio.

Favorable safety and tolerability profile with no additional safety signals

• Overall safety and tolerability were favorable and consistent with previous clinical studies of mazdutide. The most commonly reported adverse events were gastrointestinal adverse events, mostly mild to moderate. No new safety signals were identified.
• The incidence of hypoglycemia events was low, most of which were Grade 1 hypoglycemia (3.0 mmol/L ≤ blood glucose < 3.9 mmol/L). No severe hypoglycemia events were reported.

Professor Dalong Zhu, the leading principal investigator of the study, Affiliated Drum Tower Hospital, Medical School of Nanjing University, stated, "Patients with T2D often have multiple chronic conditions, including obesity, hyperlipidemia, coronary heart disease, hypertension, etc. Effective disease management should encompass the control of blood glucose, blood lipid, blood pressure and other aspects. The multifaceted benefits of multi-target GLP-1 drugs have garnered significant interest from both the research and clinical communities. As a novel GLP-1R/GCGR dual-target agonist, mazdutide not only demonstrated significant glucose-lowering effects in DREAMS-1 study, but also provided a range of comprehensive benefits including reduction in body weight, blood lipids, blood pressure, liver enzymes, etc., while maintaining favorable safety and tolerability. I hope that mazdutide will be marketed as soon as possible to help Chinese T2D patients achieve target blood glucose levels multiple metabolic benefits."

Professor Jiajun Zhao, the leading principal investigator of the study, Shandong Provincial Hospital, stated, "China has the highest prevalence of diabetes globally with more than 140 million people living with diabetes. The number continues to rise annually, presenting a challenge in disease prevention and management. There is an urgent need for innovative medications that offer enhanced efficacy and comprehensive benefits. In the treatment of Chinese patients with T2D, mazdutide showed excellent glucose-lowering effects and multiple metabolic benefits. Under long-term treatment, its efficacy, safety and tolerability remained consistently stable. The results of DREAMS-1 provide significant medical evidence supporting the use of next-generation multi-target GLP-1R/GCGR drugs for treating T2D. I believe mazdutide will offer a superior therapeutic option for Chinese patients with T2D in future."

Dr Lei Qian, Vice President of Clinical Development of Innovent, stated,  "Mazdutide is the first and fastest-developed GLP-1R/GCGR dual agonist in the world, and we are actively promoting the development of mazdutide for weight loss, T2D and other indications. The results of DREAMS-1 provided high-quality, compelling evidence for T2D treatment in China, particularly in previously untreated patients whose blood glucose was inadequately controlled with diet and exercise alone. The results of another Phase 3 study DREAMS-2, involving patients with T2D inadequately controlled by oral antidiabetic drugs (OADs), met the study endpoints in May 2024. Together, the two studies demonstrate mazdutide's comprehensive efficacy in improving glycemic control, promoting weight loss, and enhancing metabolic outcomes in patients with T2D. Detailed data will be published at academic congresses or academic journals. Meanwhile, we look forward to the performance of mazdutide in the DREAMS-3 study, a head-to-head study with semaglutide."

About Diabetes

According to the global overview of diabetes published by the International Diabetes Federation in 2021, China ranks first in number of patients with diabetes globally, with an estimated number of more than 140 million in 2021 and 174 million in 2045^[1]. Poor glycemic control can lead to irreversible microvascular and macrovascular complications, such as decreased visual acuity, blindness, renal dysfunction, peripheral neuropathy, myocardial infarction, stroke and amputation^[2]. The high prevalence of diabetes, along with its serious complications, poses a significant threat to human health. At present, there are many therapeutic regimens for diabetes. In addition to effectively controlling blood glucose, the development of new hypoglycemic drugs has begun to include the additional benefits of weight loss, cardiovascular risk reduction and kidney protection for patients with diabetes^[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.

In February 2024, the first NDA of mazdutide was accepted by the CDE of China's NMPA for chronic weight management in adults with obesity or overweight.

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 treat some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 4 new drug applications under the NMPA 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 leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte 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

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SOURCE Innovent Biologics

FAQ

What were the results of Innovent's Phase 3 DREAMS-1 trial for mazdutide in type 2 diabetes?

The DREAMS-1 trial met its primary endpoint, showing superior glycemic control with mazdutide compared to placebo. At week 24, HbA1c reduction was 1.57% for 4 mg and 2.15% for 6 mg of mazdutide, versus 0.14% for placebo. The drug also demonstrated significant weight loss and multiple cardiometabolic benefits.

When does Innovent plan to submit the NDA for mazdutide to treat type 2 diabetes?

Innovent plans to submit a new drug application (NDA) for mazdutide to treat type 2 diabetes to China's National Medical Products Administration (NMPA) in the near term, following the acceptance of its first NDA for chronic weight management in February 2024.

What were the safety results for mazdutide in the DREAMS-1 trial?

Mazdutide showed a favorable safety and tolerability profile consistent with previous clinical studies. The most common adverse events were gastrointestinal, mostly mild to moderate. The incidence of hypoglycemia was low, with no severe hypoglycemia reported. No new safety signals were identified.

How does mazdutide compare to other diabetes treatments in clinical trials?

In the DREAMS-2 trial, mazdutide showed superiority compared to dulaglutide for glycemic control, weight loss, and multiple cardiometabolic benefits in T2D patients. Additionally, a head-to-head study (DREAMS-3) comparing mazdutide with semaglutide is ongoing.