Head-to-Head Superiority to High-Dose Dulaglutide: Innovent’s First Phase 3 Clinical Trial of Mazdutide in Chinese Patients with Type 2 Diabetes Met Primary Endpoints, Company Says

SAN FRANCISCO and SUZHOU, China, May 9, 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 illnesses, announces that the Phase 3 clinical trial (DREAMS-2) of mazdutide (Innovent R&D code: IBI362), a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese subjects with type 2 diabetes (T2D) met the primary endpoint. The study results showed that mazdutide was superior to dulaglutide for glycemic control, and mazdutide also demonstrated several cardiometabolic benefits in T2D patients including weight loss, blood lipid, blood pressure, serum uric acid, liver enzymes, etc.

DREAMS-2 (ClinicalTrials.gov, NCT05606913) is a multicenter, randomized Phase 3 clinical trial to evaluate the efficacy and safety of mazdutide and dulaglutide in Chinese subjects with T2D who have inadequate glycemic control with metformin monotherapy or combination therapy of metformin with other oral agents. The trial enrolled 731 subjects to receive either mazdutide 4.0 mg, mazdutide 6.0 mg or dulaglutide 1.5 mg for 28 weeks. The primary endpoint was the change from baseline to week 28 in glycated hemoglobin (HbA1c) levels. The trial used a non-inferiority design, and additional superiority testing was conducted after non-inferiority was established.

The main endpoint was successfully met, demonstrating a robust glucose-lowering efficacy of mazdutide

After 28 weeks of treatment, mazdutide 4.0 mg and mazdutide 6.0 mg showed non-inferiority to dulaglutide 1.5 mg in terms of improvement in HbA1c level from baseline. Based on these results, the superiority test was further conducted, and both mazdutide 4.0 mg and 6.0 mg demonstrated superiority to dulaglutide 1.5 mg.

The key secondary endpointsshowed mazdutide’s superior benefits in both glucose reduction and weight loss

Statistical superioritybecame performed in the following endpoints in each mazdutide 4.0 mg and mazdutide 6.0 mg groups after 28 weeks of treatment, along side the commerce from baseline in HbA1c (superiority), percent commerce from baseline in body weight, proportion of subjects with HbA1c *.

Mazdutide showed comprehensive advantages beyond glucose reduction and weight loss in several cardiometabolic indicators (blood pressure, blood lipids, serum uric acid, and liver enzymes)

Mazdutide also demonstrated significant advantages compared to dulaglutide across various indicators, including the proportion of subjects with HbA1c ≤ 6.5%, changes in fasting blood glucose and seven-point fingerstick blood glucose from baseline, the proportion of subjects with body weight loss of ≥ 5% and ≥ 10%, absolute change in body weight from baseline, waist circumference, body mass index (BMI), systolic blood pressure (SBP), triglyceride (TG), serum uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), etc.

Favorable safety and tolerability profile

• Gastrointestinal adverse reactions were the most common adverse events, most were mild to moderate in severity, transient, and primarily occurred during the initial 12-week titration period.
• No severe hypoglycemia occurred; the incidence of moderate or severe hypoglycemia became comparable to that of dulaglutide; and the incidence of hypoglycemia became lower in indirect comparison to that reported in registrational experiences of different GLP-1 pills.
• No signal of increased cardiovascular risk for the duration of the treatment period, similar to dulaglutide.
• The overall safety profile was consistent with that observed in previous clinical experiences of mazdutide and no new safety alerts were observed.

Mazdutide is the principal GLP-1R/GCGR dual agonist in the regulatory review process, with the principal new drug application (NDA) for chronic weight management under review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). DREAMS-2, as one of the registrational clinical trials of mazdutide, will provide high-quality evidence of mazdutide for Chinese patients with T2D. Innovent plans to read out the results of another DREAMS-1 Phase 3 clinical trial in mid-2024 and submit to the CDE an NDA for the treatment of T2D with mazdutide. Detailed data from the DREAMS-1 and DREAMS-2 trials will be further analyzed and presented at academic conferences or published in scientific journals.

Professor Lixin Guo the main investigator of the scientific study, Division of Endocrinology in Beijing Clinical Institution, said: “In China, T2D patients frequently have a range of chronic illnesses as comorbidities, such as obesity, hyperlipidemia, coronary heart disease, hypertension and so on. Therefore, the management of T2D should also consider improvements in blood glucose, blood lipid, blood pressure and other aspects. In endocrine and CVM areas, GLP-1-based drugs are the hotspot of research and development for the healthcare industry as well as for clinicians, especially multi-purpose drugs which may be more efficacious and may provide more metabolic benefits. DREAMS-2 is the first Phase 3 clinical study head-to-head with dulaglutide in China which has high scientific significance and academic value. The results of this study showed that mazdutide, compared to dulaglutide, has a stronger glucose-lowering effect and favorable safety profile. More importantly, mazdutide provided more comprehensive benefits in weight loss, blood lipid, blood pressure, blood uric acid, liver enzymes and other aspects. I look forward to the NDA submission of mazdutide in T2D, and hope it will help millions of diabetic patients in China.”

Professor Yang Wenying, the main investigator of the scientific study, Division of Endocrinology inChina Japan Friendship Hospital, said: “China has the largest number of T2D patients in the world, and the prevalence of T2D among adults in China has reached 11.9%. In conjunction with other investigators of the DREAMS-2 study, I am pleased to report that mazdutide, as a new generation of GLP-1R/GCGR dual agonist, has met the primary endpoint and demonstrated superiority in change from baseline in HbA1c and several metabolic benefits when compared with dulaglutide. DREAMS-2 is a landmark study because it is the first successful registrational study of a GLP-1R/GCGR dual agonist in T2D. I believe that in the future, mazdutide will provide a new and better option for the treatment of type 2 diabetes in China.”

Dr. Lei Qian, Vice President of Clinical Development of Innovent,said: “There is a large population of diabetes in China. Innovative drugs that are more effective, safer and more convenient are urgently needed. In the DREAMS-2 study, mazdutide showed complete superiority to dulaglutide, one of the most widely prescribed glucose-lowering drugs in the world. We will further analyze the study data, and aim to submit an NDA for T2D as soon as feasible this year, in order to help more Chinese T2D patients achieve target blood glucose levels and gain metabolic benefits. At the same time, 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 worldwide overview of diabetes published by the International Diabetes Federation in 2021, China ranks first in the 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 result in irreversible microvascular and macrovascular complications, such as reduced visual acuity, blindness, kidney dysfunction, peripheral neuropathy, myocardial infarction, stroke and amputation ^[2]. The high incidence of diabetes, with serious complications, poses a significant threat to human health. Currently, there are many therapeutic regimens for diabetes. In addition to effectively controlling blood glucose, the development of modern 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 queer license agreement with Eli Lilly and Firm (Lilly) for the trend and doable commercialization of OXM3 (frequently identified as mazdutide), a GLP-1R and GCGR dual agonist, in China. As a mammalian oxyntomodulin (OXM) analogue, to boot to the outcomes of GLP-1 receptor agonists on promoting insulin secretion, reducing blood glucose and reducing body weight, mazdutide also can just furthermore develop vitality expenditure and toughen hepatic burly metabolism thru the activation of glucagon receptor. Mazdutide has demonstrated tough weight loss and glucose-reducing leads to scientific experiences, to boot to a few of cardio-metabolic advantages, along side reducing waist circumference, blood lipids, blood strain, blood uric acid, liver enzymes, liver burly inform material and improving insulin sensitivity. Currently, a entire of 5 Piece 3 registrational experiences are underway, along side GLORY-1 (4 mg and 6 mg) in Chinese language chubby or chubby subjects, GLORY-2 (9 mg) in Chinese language chubby subjects, DREAMS-1, DREAMS-2, and DREAMS-3 (mazdutide in subjects with model 2 diabetes). Amongst them, GLORY-1 uncover about and DREAMS-2 uncover about fill reached the endpoints.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to develop high-quality biologics that are more affordable for all. The company discovers, develops, manufactures and commercializes innovative medicines that address some of the most intractable diseases. Its pioneering therapies target cancer, cardiovascular and metabolic, autoimmune and ophthalmic diseases. Innovent has 10 products on the market, 3 new drug applications under NMPA review, 5 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 business practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical products can become broadly accessible. For more details, visit www.innoventbio.com or follow Innovent on Facebook and LinkedIn.

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

* Stamp: That is primarily based entirely on efficacy estimand. The uncover about historical efficacy estimand and treatment-regimen estimand for statistical diagnosis, they most frequently showed a high level of concordance in the conclusions.

Forward-taking a be conscious observation

This news release may contain forward-looking statements which 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 such forward-looking statements. The Company does not intend to update these forward-looking statements frequently.

These ahead-taking a be conscious statements are primarily based entirely on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the administration of the Firm with appreciate to future events at the time these statements are made. These statements are no longer a guarantee of future dispositions and are discipline to risks, uncertainties and other factors, some of which would possibly perchance be past the Firm’s control and are subtle to foretell. Which capability, right results also can just range materially from details contained in the ahead-taking a be conscious statements due to this of future adjustments or dispositions in our industry, the Firm’s aggressive environment and political, financial, factual and social prerequisites.

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References:

[1]. . . . Solar H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and initiatives for [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