Monday, July 15, 2024

Innovent Presents the Results of the First Phase 3 Study of Mazdutide for Weight Management at the ADA's 84th Scientific Sessions

SAN FRANCISCO and SUZHOU, China, June 25, 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, presents the key results of the first Phase 3 clinical trial of mazdutide in Chinese adults with overweight or obesity (GLORY-1) at the ADA Scientific Sessions 2024. 

The primary endpoints and all key secondary endpoints of GLORY-1 were met, reconfirming the unique advantages of the GLP-1R/GCGR dual agonist

Mazdutide (Innovent R&D code: IBI362) is a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist. By activating GLP-1R, it reduces appetite and delays gastric emptying, thereby achieving weight loss. At the same time, through activation of GCGR, it increases energy expenditure, enhances fatty acid oxidation and lipolysis, and reduces liver fat.

The results of the GLORY-1 study demonstrated that mazdutide not only induced robust weight loss in adults with obesity or overweight, but also reduced liver fat content and multiple cardiometabolic risk factors. Its first new drug application (NDA) for chronic weight management is under review by the CDE of the National Medical Products Administration (NMPA). Mazdutide, once approved, is expected to provide a safe and convenient medication for adults with obesity or overweight to effectively reduce body weight while providing cardiovascular and metabolic benefits.

Full results and analysis of GLORY-1 will be published at peer-reviewed academic journals. At present, over 1,500 subjects have received doses of mazdutide in 17 clinical trials, providing solid clinical evidence for weight management and diabetes treatment in China.

GLORY-1 (NCT05607680) is a multi-center, randomized, double-blind, placebo-controlled Phase 3 clinical trial to evaluate the efficacy and safety of mazdutide in Chinese adults with overweight or obesity. A total of 610 participants were randomized to receive mazdutide 4 mg, 6 mg or placebo in the 48-week double-blind treatment period.

Mazdutide showed robust weight loss efficacy

At week 32 and week 48, the weight loss efficacy of mazdutide 4mg and 6mg were superior to placebo in the mean percentage change in body weight from baseline, and percentage of participants achieved body weight reduction ≥5%, ≥10% and ≥15% (P<0.001). At week 48, the treatment difference for the mean percentage weight change between mazdutide 6 mg and placebo was -14.31% for the treatment-policy estimand and -14.37% for the efficacy estimand. Further details can be found in the table below:

Treatment-policy estimand*

Efficacy estimand†

Mazdutide

4 mg (N=203)

Mazdutide

6 mg (N=202)

Placebo (N=205)

Mazdutide

4 mg (N=203)

Mazdutide

6 mg (N=202)

Placebo (N=205)

Primary endpoints‡¶

Percentage change from baseline in body weight at week 32, LS mean, %

−10.09

−12.55

0.45

−10.97

−13.38

−0.24

    Treatment difference versus placebo (97.5% CI)

−10.54

(−12.01,−9.08)

−13.00

(−14.49,−11.51)

−10.72

(−12.21, −9.23)

−13.14

(−14.64, −11.64)

Percentage achieving weight reduction of 5% or more at week 32, %§

73.9

82.0

10.5

76.3

84.0

10.9

Weight-related key secondary endpoints‡¶

Percentage change from baseline in body weight at week 48, LS mean, %

−11.00

−14.01

0.30

−12.05

−14.84

−0.47

    Treatment difference versus placebo (97.5% CI)

−11.30

(−13.06, −9.54)

−14.31

(−16.11, −12.51)

−11.58

(−13.38, −9.79)

−14.37

(−16.18, −12.56)

Percentage achieving weight reduction of 5% or more at week 48, %§

71.6

81.6

10.8

73.5

82.8

11.5

Percentage achieving weight reduction of 10% or more at week 48, %§

53.5

66.7

2.6

55.2

67.9

2.9

Percentage achieving weight reduction of 15% or more at week 48, %§

35.7

49.5

2.0

37.0

50.6

2.1

LS, least squares;

* The treatment policy estimand represents the average treatment effect of mazdutide relative to placebo regardless of the adherence to treatment. For analyses related to the treatment-regimen estimand, analysis of covariance (ANCOVA) was used for continuous endpoints and logistic regression was used for binary endpoints.

† The efficacy estimand represents the average treatment effect of mazdutide relative to placebo had participants remained on their randomized treatment for the entire planned 48 weeks treatment duration. Missing data were implicitly handled by using a mixed model for repeated measures (MMRM) under the assumption of missing at random.

§ The percentage was calculated with the use of Rubin’s rules by combining the percentages of participants who met the target in imputed data sets.

¶ P<0.0001 (2-sided) for superiority comparison versus placebo, controlled for type I error rate.

 

Mazdutide treatment was associated with reductions in multiple cardiometabolic risk factors

For the efficacy estimand (P<0.001 for comparisons),

At week 48, the change from baseline to week 48 in waist circumference was −9.48 cm with mazdutide 4 mg, −10.96 cm with mazdutide 6 mg and −1.48 cm with placebo; At week 48, pooled mazdutide group (4mg and 6mg) significantly reduced multiple indicators of cardiometabolic risk factors compared with placebo, including systolic blood pressure (−9.21 mmHg vs. −2.46 mmHg), triglycerides (−0.68 mmol/L vs. -0.16 mmol/L), total cholesterol (-0.32 mmol/L vs. 0.13 mmol/L), low-density lipoprotein cholesterol (-0.22 mmol/L vs. 0.09 mmol/L), serum uric acid (−44.79 µmol/L vs. 5.96 µmol/L) and ALT (−14.50 U/L vs.-4.50 U/L);

Mazdutide showed marked reductions of liver fat content

As shown in an exploratory analysis of GLORY-1(1857-LB), in participants with baseline MRI-PDFF ≥10%, the liver fat content in mazdutide 6mg group was reduced by 80.2% on average, compared with 5.3% with placebo.

The overall tolerability and safety profile of mazdutide was favorable with no new safety signals observed

Mazdutide was well tolerated. 1.5%, 0.5% and 1.0% of participants in the mazdutide 4 mg group, mazdutide 6 mg group and placebo group discontinued the study drug prematurely due to AEs. The safety profile was consistent with that observed in previous studies of mazdutide, with no new safety signals observed. The most frequently reported adverse events were gastrointestinal (nausea, diarrhea and vomiting), mostly mild or moderate in severity and occurring during dose escalation. The incidence of serious adverse events was low and comparable to placebo. Mean changes from baseline in heart rate were no more than 5 beats/min throughout the 48-week treatment period for both the mazdutide 4mg and 6mg groups. The mean change from baseline to week 48 in heart rate were 1.6 beats/min in both mazdutide 4 mg and 6 mg groups. No safety signal of increased cardiovascular risk was observed during treatment.

Professor Linong Ji, the leading principal investigator of the study, Peking University People’s Hospital, stated, "Overweight and obesity are risk factors for several comorbidities, the most frequent of which include fatty liver disease, prediabetes, dyslipidemia, hypertension and hyperuricemia[i]. Medical evidence suggests that lifestyle management combined with pharmacotherapy for weight loss can improve metabolic and cardiovascular risk factors and thereby improve health outcomes. GLORY-1 is the first Phase 3 clinical study of mazdutide, which reconfirmed its excellent weight loss efficacy, multiple metabolic benefits improvement and good safety profile, and also indicated its potential to reduce obesity related comorbidities. I hope for the successful launch of mazdutide to swiftly benefit hundreds of millions of adults with overweight or obesity."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated, "We are excited to present GLORY-1 study results at ADA. GLORY-1 demonstrates that the GLP-1R/GCGR dual agonist mazdutide could be a safe and tolerable medication that aids obese or overweight individuals in reducing excess weight, liver fat content, and other risk factors associated with obesity-related comorbidities. We will also publish results of mazdutide in type 2 diabetes later this year. Innovent will continue to build out our next-generation product pipeline in the cardiovascular and metabolic (CVM) therapeutic area, supporting people’s pursuit of a healthier life."

About Obesity

As a chronic disease with a complex etiology, obesity is a leading risk factor for type 2 diabetes, fatty liver, cardiovascular and cerebrovascular diseases, kidney diseases, joint diseases, sleep apnea and various cancers. With economic development and lifestyle changes, the number of obese populations in China has jumped to the highest in the world[ii]. The incidence and mortality of cardiovascular disease, type 2 diabetes and certain tumors are also higher in populations with severe obesity. Deaths caused by overweight and obesity accounted for 11.1% of deaths related to chronic non-communicable diseases in 2019, a significant increase from 5.7% in 1990[iii]. Overweight and obesity have become serious health problems. Lifestyle intervention is a basic treatment option for patients with overweight or obesity. However, a considerable percentage of patients fail to achieve their desired weight loss goals through merely lifestyle intervention and may require pharmacological intervention. Traditional pharmacological therapies in China have limited efficacy and pose multiple safety concerns, underscoring the unmet clinical need for more effective and safe treatments for the Chinese obese population.

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, with the effects of GLP-1 receptor agonists to promote 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 robust weight loss and glucose-lowering effects in clinical studies as well as improvements in multiple cardio-metabolic indicators including reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, liver fat content and improved insulin sensitivity. Currently, five Phase 3 studies of mazdutide in Chinese adults with overweight or obesity (GLORY-1 and GLORY-2) and type 2 diabetic (DREAMS-1, DREAMS-2 and DREAMS-3) subjects are underway, where GLORY-1 and DREAMS-2 studies have met the primary and all key secondary endpoints.

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.

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 10 products in the market. It has 4 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.

Forward-looking statement

This news release may contain certain forward-looking statements that are, by their nature, participant 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 participant 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

[i] Chen K, Shen Z, Gu W, Lyu Z, Qi X, Mu Y, Ning Y; Meinian Investigator Group. Prevalence of obesity and associated complications in China: A cross-sectional, real-world study in 15.8 million adults. Diabetes Obes Metab. 2023 Aug 17. doi: 10.1111/dom.15238. Epub ahead of print. PMID: 37589256.

[ii] Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol 2021; 9: 373–92.

[iii] Institute for Health Metrics and Evaluation. Global Health Data Exchange. GBD results tool. http://ghdx.healthdata.org/gbd-resultstool (accessed Jan 10, 2021).

 

Source : Innovent Presents the Results of the First Phase 3 Study of Mazdutide for Weight Management at the ADA's 84th Scientific Sessions

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