Gan & Lee Pharmaceuticals recently announced positive Phase 2 clinical trial results for three innovative drugs—GZR18 injection, GZR4 injection, and GZR101 injection—in adult patients with Type 2 diabetes (T2D) in China. These trials demonstrated that the drugs achieved superior or comparable efficacy in lowering glycated hemoglobin (HbA1c) compared to their respective comparator drugs.
GZR18 Injection: GLP-1 Receptor Agonist
A Phase 2b multicenter, randomized, open-label study (CTR20232069) evaluated the efficacy and safety of bi-weekly GZR18 injection versus once-weekly semaglutide (Ozempic®) in 264 Chinese adults with T2D whose glycemic control was poor despite lifestyle interventions, unregulated use of anti-diabetic drugs, or oral anti-diabetic treatment for at least three months. Patients received bi-weekly GZR18 injections (12 mg, 18 mg, or 24 mg), once-weekly 24 mg GZR18 injections, or 1 mg semaglutide for 24 weeks, including a dose-escalation period. The primary efficacy endpoint was the change in HbA1c from baseline after 24 weeks.
After 24 weeks, the mean HbA1c reduction from baseline in the GZR18 groups was 1.87% (12 mg, bi-weekly), 2.28% (18 mg, bi-weekly), 1.94% (24 mg, bi-weekly), and 2.32% (24 mg, once-weekly), all higher than the semaglutide group (1.60% reduction). In treatment-naïve patients with poor glycemic control on lifestyle interventions, the HbA1c reduction in the bi-weekly GZR18 injection group reached 2.98%, compared to 2.04% in the semaglutide group (p < 0.05). Patients in the bi-weekly GZR18 group also experienced a maximum weight loss of 5.42 kg, compared to 3.25 kg in the semaglutide group. GZR18 also improved fasting glucose, blood pressure, and lipid levels. The drug was generally well-tolerated, with safety and tolerability consistent with known GLP-1 receptor agonists. The most common adverse events were gastrointestinal-related, and no severe hypoglycemic events were observed.
GZR4 Injection: Basal Insulin Analog
The Phase 2 trial (CTR20232431) was a multicenter, randomized, open-label, parallel-group study evaluating the efficacy, tolerability, and safety of once-weekly GZR4 injections versus once-daily insulin degludec (Tresiba®) in 83 T2D patients with poor glycemic control on oral antidiabetic drugs (Part A) and 96 T2D patients with poor glycemic control on a combination of oral antidiabetic drugs and basal insulins (Part B).
In part A, the mean HbA1c reduction of once-weekly GZR4 injection was 1.50%, comparable to insulin degludec’s reduction of 1.48%. In part B, GZR4 injection demonstrated a superior HbA1c reduction of 1.26%, compared to -0.87% for insulin degludec (treatment difference: -0.38%, p < 0.01). Improvements in time-in-range (TIR) were comparable between GZR4 and insulin degludec. GZR4 injection showed good safety and tolerability, with no severe hypoglycemic events observed.
GZR101 Injection: Premixed Dual Insulin Analog
The Phase 2 clinical trial (CTR20232431) was a multicenter, randomized, open-label, parallel-controlled, treat-to-target study. Part A compared the efficacy, safety, and tolerability of GZR101 injection administered once-daily versus insulin degludec/insulin aspart (Ryzodeg®) administered once-daily over 16 weeks in 62 patients with uncontrolled T2D on oral anti-diabetic drugs. Part B compared the efficacy, safety, and tolerability of GZR101 injection combined with insulin aspart versus insulin degludec/insulin aspart (Ryzodeg®) administered twice-daily over 16 weeks in 91 patients with uncontrolled T2D on basal/premixed insulin.
In Part A, the HbA1c levels in the once-daily GZR101 injection group decreased by 1.56%, superior to the -1.31% reduction in the once-daily insulin degludec/insulin aspart group (treatment difference: -0.24%). In Part B, GZR101 injection combined with insulin aspart achieved HbA1c reductions of -1.64% (once-daily insulin aspart) and -1.68% (twice-daily insulin aspart), both higher than the -1.59% reduction in the twice-daily insulin degludec/insulin aspart group (treatment differences of -0.06% and -0.09%, respectively). GZR101 injection demonstrated comparable efficacy to insulin degludec/insulin aspart in controlling fasting and postprandial blood glucose, as well as improving time-in-range (TIR). The estimated incidence of hypoglycemic events in both groups did not show statistically significant differences during the study.
"The positive results achieved by GZR18, GZR4, and GZR101 in Phase 2 clinical trials mark an important milestone in improving the current landscape of diabetes treatment," said Dr. Zhong-ru Gan, Chairman of Gan & Lee Pharmaceuticals. "These results demonstrate that our three products provide better glycemic control compared to similar antidiabetic drugs."
