Hua Medicine has announced positive results from a Phase I clinical trial in the U.S. for its second-generation glucokinase activator (GKA) candidate, HM-002-1005, a prodrug of dorzagliatin (HMS5552), for the treatment of Type 2 diabetes (T2D). The randomized, double-blind, placebo-controlled, single-dose study, which included 40 subjects with T2D, focused on evaluating the safety, tolerability, and pharmacokinetics of the drug.
The study aimed to develop a once-daily oral administration formulation that extends the drug's action, enhances patient compliance, and prolongs the stimulation of GLP-1 secretion in the intestines. The results indicate that HM-002-1005 tablets are rapidly converted to HMS5552 in the human body, with minimal prodrug exposure in blood and urine. The biological half-life (t1/2) of HMS5552 after a single dose of HM-002-1005 was prolonged compared to dorzagliatin tablets.
Key Pharmacokinetic Findings
Data showed that the maximum plasma concentration (Cmax) of HMS5552 after a 184.5mg single dose of HM-002-1005 was comparable to that achieved with a 75mg single dose of dorzagliatin. Similarly, the daily area under the curve (AUC) of HMS5552 in plasma after a single dose of HM-002-1005 was comparable to the exposure level seen with a 75mg twice-daily (BID) dose of dorzagliatin. These findings suggest that HM-002-1005 is nearly completely converted to HMS5552 in humans, supporting its potential for once-daily administration.
Implications for Treatment
The development of HM-002-1005 aims to improve patient adherence and provide effective 24-hour blood glucose control. Furthermore, the company believes that the new formulation offers the opportunity to explore higher doses (above 150mg daily) to potentially achieve better efficacy. According to Hua Medicine, the original 75mg BID dose regimen of dorzagliatin was developed based on the concept of a Minimum Therapeutic Effective Dose in Chinese T2D patients, who often present with impaired insulin secretion and a significant reduction in early-phase insulin release. The company anticipates that the different disease characteristics of T2D with obesity in Western patient populations may benefit from dorzagliatin's effects on GLP-1 secretion and improvement of insulin sensitivity.
Future Development Plans
With the confirmation that the exposure level of HM-002-1005 at 184.5mg is comparable to dorzagliatin at 75mg BID, Hua Medicine plans to further optimize the dosage form, followed by a Multiple Ascending Dose (MAD) clinical development of the second-generation GKA in both China and the United States.
Executive Perspective
Dr. Li Chen, founder and CEO of Hua Medicine, commented on the results, stating that the company remains committed to treating Type 2 diabetes at its root cause by restoring patients’ ability to autonomously regulate blood glucose levels. He added that the company will undergo a strategic upgrade by further exploring the therapeutic potential of GKA, enriching its product pipeline, and seeking partnerships to expand into global markets and establish the brand identity of GKA medications.
