Innovent Announces Publication of Mazdutide (IBI362) Phase 2 Full Results in Chinese Patients with Type 2 Diabetes in Diabetes Care

ROCKVILLE, Md.and SUZHOU,China, Nov. 22, 2023 /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, metabolic, autoimmune, ophthalmology and other major diseases, announces that full results from a Phase 2 clinical trial of mazdutide (Innovent R&D code: IBI362), a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese patients with type 2 diabetes (T2D) were published in Diabetes Care.

Professor Wenying Yang, the corresponding author, principal investigator of the study from China-Japan Friendship Hospital, stated, "The rate of achieving target blood glucose control in Chinese patients with T2D is still low. T2D is often accompanied by a variety of cardiometabolic risk factors, such as obesity, hyperlipidemia, coronary heart disease, fatty liver, and gout. Those comorbidities not only increase the disease burden, but also add to the difficulty and complexity of treatment. There is an urgent clinical need for safe, efficacious and innovative medicines to treat diabetes that offer improved patient convenience, weight loss effect, multiple cardiometabolic benefits and low hypoglycemic risk. The Phase 2 full results of mazdutide, published in Diabetes Care, not only demonstrated its robust efficacy in glycemic control but also the advantage to reduce HbA1c and body weight at the same time in Chinese patients with T2D, suggesting additional benefits to diabetes patients living with obesity. This 20-week phase 2 study also shows multiple cardiometabolic benefits and favorable safety profile brought by mazdutide treatment. I look forward to more encouraging results from two ongoing Phase 3 studies of mazdutide in Chinese patients with T2D, potentially bringing this novel treatment option to patients as soon as possible."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated, "The publication in a top-tier medical journal in the field of diabetes is another important achievement for mazdutide as potential first-in-class GLP-1R/GCGR dual agonist. This Phase 2 study in Chinese patients with T2D demonstrated mazdutide's differentiated advantage as a dual agonist that not only lowers glucose, but also controls weight and brings multiple cardiometabolic benefits for T2D patients. Furthermore, the consistently favorable safety profile further validates the good safety and tolerability of this novel molecule as observed in accumulated studies. Notably, we compared the efficacy of mazdutide with dulaglutide in this phase 2 study, and obtained encouraging results, reinforcing our confidence in mazdutide's potential. The registrational Phase 3 studies of mazdutide in Chinese T2D patients (DREAMS-1 and DREAMS-2) are currently underway, and will provide further critical clinical evidence in Chinese T2D patients. We hope that this high-quality medicine will benefit Chinese patients living with T2D as soon as possible. "

In this randomized, double-blind, placebo-controlled Phase 2 trial (ClinicalTrials.gov, NCT04965506), a total of 252 patients with T2D inadequately controlled with diet and exercise alone or with stable metformin (glycated hemoglobin A1c [HbA1c] 7.0–10.5%) were randomly assigned to receive 3 mg mazdutide, 4.5 mg mazdutide, 6 mg mazdutide, 1.5 mg open-label dulaglutide, or placebo subcutaneously for 20 weeks. The primary outcome was change in HbA1c from baseline to week 20. The mean BMI baseline was 27.4 kg/m² and mean HbA1c baseline was 8.06% for participants who received at least one dose of study treatment (n=250).

All doses of mazdutide significantly reduced HbA1c levels compared with placebo. 

• The mean change from baseline to week 20 in HbA1c levels were −1.41% with mazdutide 3 mg, −1.67% with mazdutide 4.5 mg, and −1.55% with mazdutide 6 mg (−1.35% with dulaglutide and 0.03% with placebo). The reductions in HbA1c were significantly greater with mazdutide compared with placebo (all P<0.0001).
• Meanwhile, the proportion of patients with HbA1c ＜7.0% at week 20 were 54.0%, 66.7% and 73.5% with mazdutide 3 mg, 4.5 mg and 6 mg, respectively (60.0% with dulaglutide and 17.6% with placebo); The proportion of patients with HbA1c ≤6.5% at week 20 were 28.0%, 56.3% and 51.0% with mazdutide 3 mg, 4.5 mg and 6 mg, respectively (46.0% with dulaglutide and 7.8% with placebo).
• Furthermore, mazdutide also significantly reduced fasting plasma glucose and 2-hour postprandial glucose.

All doses of mazdutide significantly reduced body weight along with HbA1c target. 

• The mean percent change from baseline to week 20 in body weight were −4.12%, −5.31%, and −7.11% with mazdutide 3 mg, 4.5 mg and 6 mg, respectively (−2.69% with dulaglutide and −1.38% with placebo).
• Meanwhile, the proportion of patients with body weight loss of ≥5% at week 20 were 24.0%, 37.5% and 57.1% with mazdutide 3 mg, 4.5 mg and 6 mg, respectively (18.0% with dulaglutide and 9.8% with placebo);
• At week 20, 16.0% with mazdutide 3 mg, 29.2% with mazdutide 4.5 mg and 49.0% with mazdutide 6 mg achieved body weight loss of ≥5% and HbA1c of <7.0% (12.0% with dulaglutide and 0 with placebo).

Mazdutide was safe and well-tolerated.

• No patient discontinued study drug due to adverse events. No investigator-judged study drug-related serious adverse event occurred. No severe hypoglycemia events occurred.
• The overall safety profile of mazdutide was similar to those observed in previous studies of mazdutide and other GLP-1-based drugs.
• The most frequently reported treatment-emergent adverse events included diarrhea, decreased appetite, nausea and vomiting, most of mild or moderate severity.
• At week 20, the mean increase in heart rate from baseline in mazdutide groups was comparable to that of the dulaglutide group. No signal of increased cardiovascular risk was observed.

Furthermore, mazdutide also reduced waist circumference, blood pressure, low-density lipoprotein cholesterol and triglycerides, and improved insulin sensitivity, providing comprehensive benefits to patients with T2D. Full results can be found in the Diabetes Care.

About Diabetes

The prevalence of diabetes among adults in China is 11.6%, of which type 2 diabetes accounts for about 90% of the total number of diabetic patients, and the number of patients is still increasing. Poor glycemic control will lead to irreversible microvascular and macrovascular complications such as decreased visual acuity, blindness, renal insufficiency, peripheral neuropathy, myocardial infarction, stroke, amputation, etc. As a latent disease with serious complications and high incidence, diabetes mellitus has seriously threatened human health. Currently, there are many treatment options for diabetes, and in addition to effective glycemic control, the development of new hypoglycemic drugs may also provide additional benefits for diabetic patients in terms of weight loss, cardiovascular risk reduction, and renal protection.

About Mazdutide (IBI362)

Innovent entered into a licensing 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, 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. Mazdutide has demonstrated excellent weight loss and glucose-lowering effects in clinical studies, as well as reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes and liver fat content, as well as improving insulin sensitivity, bringing multiple metabolic benefits. Currently, three key phase 3 studies of mazdutide 4 mg and 6 mg in Chinese patients with overweight or obesity (GLORY-1) and type 2 diabetic (DREAMS1 and DREAMS-2) subjects are underway. The Phase 2 clinical study of mazdutide 9 mg in Chinese patients with obesity is in progress. The Phase 3 clinical study of mazdutide 9 mg in Chinese subjects with obesity will be start at the end of 2023.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to discover and develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to discovering and developing, manufacturing and commercializing high-quality innovative medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, and ophthalmology diseases to enhance the quality of the patients' lives. Innovent has 10 products in the market, including TYVYT® (Sintilimab Injection), BYVASDA® (Bevacizumab Injection), SULINNO® (Adalimumab Injection), HALPRYZA® (Rituximab Injection), Pemazyre® (Pemigatinib Oral Inhibitor), olverembatinib, Cyramza® (Ramucirumab Injection), Retsevmo® (Selpercatinib Capsules), FUCASO® (Equecabtagene Autoleucel Injection) and SINTBILO® (Tafolecimab Injection). Additionally, 7 assets are in Phase III or pivotal clinical trials, and 17 more molecules are in early clinical stage.

Innovent has also entered into 30 strategic collaborations with Eli Lilly, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. We strive to work with many collaborators to help advance the biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/

Disclaimer:

Innovent does not recommend any off-label usage.

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.