Hua领 Pharmaceuticals Unveils Pivotal Phase III Data for Dorzagliatin, Set to Launch China's First Homegrown First-in-Class Diabetes Drug
Recently, Hua Medicine (2552.HK) announced interim data from the Phase III clinical trial of its investigational third-generation oral diabetes drug, dorzagliatin, in combination with metformin for the treatment of diabetes (HMM0302). This marks the second time in half a month that Hua Medicine has released key clinical trial data, with its stock price rising more than 12% at one point on the day.
Dorzagliatin is a global first-in-class novel drug with the potential to restore islet function, an area in which Hua Medicine has been deeply engaged since its inception. The release of the latest clinical data represents a significant milestone, both for Hua Medicine itself and for the broader trend toward precise, personalized treatment of diabetes worldwide.
Data show that the Phase III registration clinical study of dorzagliatin in combination with metformin met its primary efficacy and safety endpoints in a 24-week randomized, double-blind, placebo-controlled trial. The lead investigator of this trial is Professor Yang Wenying, a renowned endocrinologist at China-Japan Friendship Hospital. Currently, the subsequent 28-week open-label treatment phase is being conducted simultaneously across 72 clinical centers in China.
The newly released data are highly impressive: in patients with type 2 diabetes who had experienced inadequate response to maximally tolerated metformin therapy, the treatment group receiving 24 weeks of combination therapy with dorzagliatin and metformin achieved a reduction in glycated hemoglobin (HbA1c) of 1.02% from baseline, which was 0.66% greater than that observed in the placebo control group (p < 0.0001). Meanwhile, 44.4% of patients in the dorzagliatin treatment group achieved HbA1c levels below 7% (the treatment target specified by the American Diabetes Association), compared with only 10.7% among subjects receiving metformin alone. Compared with the control group, the dorzagliatin treatment group demonstrated statistically significant improvements in HbA1c response rate, HOMA2-β (a marker of β-cell function), HOMA2-IR (a marker of insulin resistance), 2-hour postprandial plasma glucose, and fasting plasma glucose. Furthermore, during the 24-week treatment period, the incidence of clinically meaningful hypoglycemia with dorzagliatin was less than 1%, and no drug-related serious adverse events occurred, demonstrating favorable safety and tolerability.
This indicates that dorzagliatin demonstrates significant efficacy in glycemic control for patients with type 2 diabetes who are either newly diagnosed or have experienced inadequate response to maximal-dose metformin therapy.
According to Hua Medicine’s plan, following the successful 52-week Phase III results from both the dorzagliatin monotherapy Phase III registrational clinical trial (HMM0301) and the HMM0302 trial, the company will submit a New Drug Application (NDA) to the National Medical Products Administration (NMPA) for dorzagliatin as a first-line treatment for diabetes in China. On June 18, Hua Medicine announced the latest clinical trial data from HMM0301, with core data analysis demonstrating that the 52-week treatment maintained long-term stable efficacy and safety.
Dorzagliatin, an investigational dual-mechanism glucokinase activator (GKA) independently developed by Hua Medicine for the treatment of type 2 diabetes, represents a new generation of therapeutic agents for this condition. This drug holds promise for effectively addressing functional impairment of glucokinase (GK), the body’s blood glucose sensor. Previous clinical studies have demonstrated its potential to improve β-cell function and halt the further progression of type 2 diabetes. Currently, no drugs with a similar mechanism of action are on the market. Even within the global GKA development landscape, Hua Medicine is the only company that has completed Phase III registrational clinical trials for its investigational dorzagliatin and advanced it to the New Drug Application (NDA) submission stage.
In 2010, Hua Medicine was founded by Dr. Chen Li. Eight years later, as the third pre-revenue biotech stock to list under the Hong Kong Stock Exchange’s new listing rules, the company made its official debut in the capital markets. Dorzagliatin is Hua Medicine’s flagship product, and the release of the latest clinical trial data for HMM0302 has undoubtedly further advanced the commercialization timeline for this novel drug.
Diabetes, an age-old disease, has long been a persistent threat to global public health. Statistics show that there are 463 million adults aged 20–79 with type 2 diabetes worldwide. Based on current growth trends, the number of adult patients with type 2 diabetes globally is projected to exceed 700 million by 2045. In recent years, the rapidly rising number of cases in China has drawn increasing global attention to the country’s diabetes epidemic. The latest national epidemiological survey, published in April in The BMJ (British Medical Journal), revealed that using glycated hemoglobin (HbA1c) ≥6.5% as the diagnostic criterion, the estimated prevalence rates of total diabetes and prediabetes among Chinese adults aged 18 and older were 12.8% and 35.2%, respectively, between 2015 and 2017.
Anti-glycation, while remaining a sustained area of human exploration, has also unlocked immense potential for the commercial pharmaceutical market. Global top-10 pharmaceutical companies such as Merck & Co. and GlaxoSmithKline have previously achieved key growth from this sector. Industry insiders told VCBeat that the market size for anti-diabetic drugs is projected to grow from RMB 51.2 billion in 2017 to RMB 173.9 billion in 2028, representing a compound annual growth rate (CAGR) of 11.8%.
Currently, the most widely used oral antidiabetic drug in clinical practice is metformin, which has a history of nearly 70 years. It is also the first-line therapy consistently recommended by diabetes treatment guidelines both domestically and internationally, offering advantages such as good efficacy, safety, tolerability, and cost-effectiveness. However, it does not address the underlying causes of diabetes, such as insulin resistance and impaired islet function.
In recent years, a new generation of antidiabetic drugs with mechanisms of action distinct from traditional agents such as metformin and insulin has been successively launched. In addition to being available as monotherapies, many of these novel antidiabetic agents have been developed into fixed-dose combination (FDC) formulations for use in conjunction with metformin. In August 2019, the updated National Reimbursement Drug List was released, incorporating multiple FDC formulations that combine metformin with vildagliptin, linagliptin, sitagliptin, saxagliptin, and other agents. After more than a decade of clinical practice, metformin-based FDCs for glycemic control have gradually gained “official recognition” through inclusion in the national medical insurance coverage.
Currently, metformin, whose patent has expired, has become a competitive arena for domestic generic drug manufacturers. However, in the market for new diabetes medications such as DPP-4 inhibitors and SGLT-2 inhibitors, there are few domestically produced drugs. Notably, all fixed-dose combination formulations of metformin recently included in the National Reimbursement Drug List are imported products. In the future, the market launch of dorzagliatin as monotherapy and in combination regimens may bring new changes to this market landscape.
According to Dr. Chen Li, glucokinase activators (GKAs), represented by dorzagliatin, feature intelligent and precise mechanisms in regulating glucose homeostasis, laying the foundation for personalized diabetes treatment. To understand the logic of GK-mediated glucose regulation, it is essential to recognize that human glucose control is a fully automated system. Through the sensing function of glucokinase (GK) in response to changes in glucose concentration, insulin and glucagon can accurately adjust their secretion based on blood glucose levels, thereby maintaining blood glucose within a homeostatic range. Furthermore, the storage and release of glucose are also facilitated by the coordinated actions of GK and the glucokinase regulatory protein (GKRP).
In other words, glucokinase (GK) is responsible for both glucose concentration sensing and the regulation of glucose metabolism. If GK function is impaired, it will lead to an imbalance in glucose homeostasis, resulting in loss of glycemic control and the development of type 2 diabetes. Previously, dorzagliatin has demonstrated potential in restoring GK function in patients with type 2 diabetes across multiple studies, holding promise for reestablishing glucose homeostasis.
Currently, there are nine glucokinase activators (GKAs) that have entered or completed Phase II clinical trials globally, while dorzagliatin is the first drug in its class to successfully complete Phase III clinical studies worldwide. Meanwhile, Hua Medicine has conducted more than 10 clinical studies on dorzagliatin in China and the United States, including trials involving monotherapy and combination therapy.
VCBeat’s research found that, in addition to combination therapy with metformin, Hua Medicine has conducted clinical trials for the treatment of type 2 diabetes using its investigational drug dorzagliatin as a cornerstone agent in combination with existing medications, including empagliflozin (an SGLT-2 inhibitor) and sitagliptin (a DPP-4 inhibitor), all of which have demonstrated positive results.
Dr. Chen Li told VCBeat that there are currently eight major classes of oral or injectable diabetes medications worldwide, each with its own advantages and disadvantages in glycemic control. Hua Medicine’s new drug development strategy is to build a “dorzagliatin+” clinical trial matrix, leveraging synergistic effects between different drugs to more effectively control the onset and progression of diabetes and its complications, thereby providing a novel therapeutic option for patients with type 2 diabetes.
In fact, in addition to offering a rich portfolio of combination therapies for diabetes, Hua Medicine is continuing to expand the scope of its “dorzagliatin+” strategy. Leveraging years of in-depth research on glucokinase activators (GKAs), the company aims to continuously deliver critical insights into fundamental diabetes research, systematic diagnostic criteria, and molecular subtyping, thereby addressing diverse needs across the entire spectrum of diabetes prevention, diagnosis, and treatment. At the 79th Scientific Sessions of the American Diabetes Association held last year, Hua Medicine showcased its artificial intelligence and machine learning capabilities, proposing six distinct subtypes of type 2 diabetes based on patient biomarkers and clinical indicators, which holds promise for meeting the need for precision medication. “In the future, we will continue to apply the ‘dorzagliatin+’ approach to integrate more resources related to blood glucose management,” stated Dr. Chen Li.
In its third year since listing on the Hong Kong Stock Exchange, Hua Medicine has been releasing key clinical data for its flagship product. This company, dedicated to the R&D of original innovative drugs, is finally approaching the harvest phase for its products, and we look forward to seeing stronger performance in its future commercialization efforts.