Hua Medicine, a leading clinical stage biotech company in Shanghai, announced today positive results in the first-ever successful Phase 2 monotherapy trial of a novel drug class called glucokinase activators (GKA). The company's 4th-generation GKA, HMS5552, targets one of the key enzymes (GK) that act as a 'glucose sensor' and regulates the pathways for carbohydrate metabolism. In addition to impressive and statistically significant efficacy data, the results showed an excellent tolerability and safety profile with low risk of hypoglycemia or other side effects common in many diabetes treatments. The 12-week Proof-of-Concept clinical study was conducted in 22 leading hospital centers across China and was led by Professor Dalong Zhu, President-elect of the Chinese Diabetes Society.
The Phase 2 clinical trial was a multicenter, randomized, double-blind, placebo-controlled, parallel 5-dose arm study that enrolled 258 Type 2 Diabetes patients. Patients were given one of the following: placebo, 75 mg QD (once-a-day), 100 mg QD, 50 mg BID (twice-a-day), or 75 mg BID doses every day for 12-week following a standardized 4-week placebo run-in period. Patients had screening HbA1c levels ranging between 7.5%-10.5% with an average of 8.37% prior to treatment. At the end of the 12-week treatment period, the least -squares mean changes of HbA1c from baseline were -0.3%, -0.5%, -0.7%, -0.8%, -1.1% for the placebo, 75 mg QD, 100 mg QD, 50 mg BID, and 75 mg BID groups, each respectively, and the results were highly statistically significant compared to placebo for all dose groups except for the lowest dose of 75 mg QD. Fasting blood glucose (FBG), post-meal glucose (PMG), and HbA1c levels all showed significant dose-dependent decreases compared to baseline, and further showed a continuing trend of decreasing beyond 12-week without rebound or a loss in durability of the drug's effect which is in sharp contrast to the durability-loss seen as early as 4 weeks from the earlier generation GKAs.
Additionally, HMS5552 showed an excellent tolerability and safety profile with very low risk of hypoglycemia. There were no drug-related serious adverse events (SAE) or cases of serious hypoglycemia, and the total adverse event (AE) rate was statistically indistinguishable from placebo rates except for the incidence of mild hypoglycemia (5.4%) which is in line with other low-risk FDA approved therapies such as DPP-IV inhibitors (2%-6% mild hypoglycemia rate). There were no significant changes to liver enzymes, lipid profiles, or other laboratory values compared to placebo nor were there any physical exam, vital sign, or ECG abnormalities."
"We are very thankful for the incredible effort put forth by Hua's operational team, CRO and SMO partners, our physician collaborators at all 22 hospital centers, and all of our participating diabetes patients who made this trial possible," stated Dr. Yi Zhang, VP Clinical R&D at Hua Medicine. "The excellent results of our clinical studies are a testament to our team's adherence to the highest international standards of quality control that always places patient health and safety as primary goals."
"After approval from regulatory authorities, we intend to initiate Phase 3 pivotal studies for HMS5552 by 1H2017. The company will also explore additional mechanistic and drug combination studies with other diabetes therapies both in the US and Europe," said Dr. Li Chen, CEO of Hua Medicine. "HMS5552 is the first 1st-in-class drug developed entirely in China for a major disease indication such as diabetes, and the completion of this Phase 2 trial marks a major milestone in accelerating drug-development innovation in China. We are proud to play a part in this continuing evolution."