Hua Medicine today announced the clinical study results of HMM0110 and HMM0111. HMM0110 was conducted in China to evaluate whether dorzagliatin can be readily used in Type 2 diabetes (T2D) patients with impaired renal function. In subjects with end stage renal disease (ESRD, eGFR < 15 mL/min/1.73 m2) and are not on dialysis, as compared to healthy subjects whose renal function is normal, the ratio of dorzagliatin Cmax and AUCinf were 0.81 (90% CI: 0.64, 1.01) and 1.10 (90% CI:0.94, 1.28) respectively, indicating no significant impact of renal impairment on subjects exposed to dorzagliatin. This result supports dorzagliatin as a promising solution and potential supplementary option for T2D patients with moderate, severe and end stage chronic kidney disease (i.e., stages 3-5 of CKD) which can provide satisfactory blood glucose control safely and without dose adjustment. Most of current oral antidiabetic drugs are not readily suitable for patients with renal impairment, especially at moderate, severe and end stages, as current oral treatments either require dose adjustment (e.g., metformin and the top-selling DPP-4 inhibitors) or are contraindicated (e.g., SGLT-2 inhibitors).
HMM0111 was a pharmacokinetic (PK) and pharmacodynamic (PD) study conducted in the United States in T2D patients with insufficiently controlled blood glucose levels with metformin, DPP-4 inhibitors or SGLT-2 inhibitors, alone or in combination therapy. Patients received dorzagliatin (75 mg BID) and sitagliptin (100 mg QD), alone or in combination. Co-administration orally of dorzagliatin and sitagliptin at steady state demonstrated no impact on their PK properties but, following OGTT, based on glucose AUEC, the combined effect (AUEC: 253 h*mg/dL) is superior to sitagliptin alone (AUEC: 378 h*mg/dL) and dorzagliatin alone (AUEC: 339 h*mg/dL) with p-value<0.05. It is also demonstrated that dorzagliatin add-on to sitagliptin increases C-peptide secretion over dorzagliatin and sitagliptin alone, suggesting a synergistic effect of improved beta cell function. This result supports the development of a combination therapy of dorzagliatin with sitagliptin in the treatment of T2D patients.
“As mentioned previously, Hua Medicine successfully achieved the primary efficacy end point of dorzagliatin in the Phase III pivotal trial (HMM0301) with desirable safety profile. Our clinical development plan of dorzagliatin as a cornerstone therapy is based on its add-on benefits to T2D patients either as monotherapy or add-on to current diabetes medicines. ” said Dr. Li Chen, Chief Executive Officer of Hua Medicine.“ The positive results from HMM0110 support the potential for dorzagliatin to be used for blood glucose control in T2D patients with stages 3-5 chronic kidney disease without dose adjustment, which presents an excellent alternative to existing oral antidiabetic medicines. The positive results of HMM0111 validates the synergy of both mechanisms of action of DPP-4 inhibitors and glucokinase activators, thereby supporting the potential for dorzagliatin in combination with the top selling oral anti-diabetic drug, sitagliptin”. Sitagliptin monotherapy and sitagliptin in combination with metformin sales were approximately US$5.9 billion in 2018 globally. “In addition to demonstrating that the combination of metformin and dorzagliatin is a viable combination therapy, the positive results of HMM0111 now demonstrates that the combination of dorzagliatin with sitagliptin will be of significant value to patients and shareholders as an attractive alternative option for T2D patients that failed to effectively control blood glucose levels when on either metformin or sitagliptin. Both excellent results of HMM0110 and HMM0111 allows Hua Medicine to advance its mission in establishing dorzagliatin as a cornerstone therapy for T2D.”
There are 435 million individuals with T2D globally, with a diagnosis rate of 54.2%. Diabetes imposes a large economic burden on the global healthcare system, costing US$850 billion globally in 2017, including but not limited to complications associated with renal failure (which has an occurrence rate of 27.09% in Chinese T2D patients in the last 5 years)1. Currently approved diabetes therapies cannot effectively control the progression of diabetics into more advanced stages of the disease and increases blood glucose fluctuation, which then leads to the many complications associated with severe diabetes, such as loss of vision, peripheral neuropathy, impaired kidney function, cardiovascular disease, and stroke. Dorzagliatin fixes the glucose sensor and restores glucose homeostasis, which has the potential to maintain glucose levels in a healthy range, thereby preventing diabetes complications.