182-OR: A Novel Dual-Acting Glucokinase Activator (GKA) Dorzagliatin (HMS5552) Achieved Primary Efficacy Endpoint with Good Safety Profiles in T2DM Patients after 24 Weeks of Treatment in a Phase III Monotherapy Trial

Abstract

GK acts as a ’glucose sensor’ to regulate glucose homeostasis. Dorzagliatin is a novel dual-acting allosteric GKA targeting both pancreatic and liver GK. The study aimed to confirm the efficacy and safety of dorzagliatin as a monotherapy in Chinese T2D patients. It is the first successful Phase III trial for a GKA. It was a multicenter, randomized, double-blind, placebo-controlled trial. 463 drug-naïve adult subjects were randomized to 75 mg dorzagliatin or placebo (2:1) BID for 24 wks. The primary endpoint was the change in HbA1c from baseline to wk 24. Secondary endpoints included 2h PPG and other glycemic variables. Safety assessment included AE, hypoglycemia, laboratory tests, ECG, etc. The MMRM results suggested the LS mean change in HbA1c from baseline at wk 24 was -1.07% in dorzagliatin group, significantly lower than the placebo group (P<0.0001). The homeostatic control rate (HbA1c <7% without hypoglycemia), was 45.0% in dorzagliatin group compared to 21.5% in placebo group (P<0.0001). At wk 24, the mean change of 2h PPG (mM) from baseline was -3.05 and -0.78 for the dorzagliatin and placebo groups (P<0.0001). The mean change of FPG (mM) from baseline at wk 24 was -0.70 in dorzagliatin group and -0.34 in placebo group with no significant difference. The change of HbA1c from baseline at each study visit was significantly lower (P<0.001) in dorzagliatin group compared with the placebo group. Dorzagliatin was well-tolerated during the 24 wks and had a good safety profile. Fewer than 1% of patients experienced incident of hypoglycemia over 24 wks. There were no death, drug-related SAEs, and severe hypoglycemia in subjects treated with dorzagliatin. Overall, dorzagliatin had a favorable effect on glycemic control and a good safety profile over 24 wks in Chinese T2D patients. It brings the reality a step further in developing a novel T2D drug with GKA mechanism of action. Disclosure D. Zhu: None. Y. Zhang: None. L. Chen: None.