Gan & Lee Pharmaceuticals has unveiled encouraging results from two Phase I clinical trials of its novel once-weekly insulin analog, GZR4. The findings, presented at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD 2024), highlight GZR4’s safety, tolerability, and efficacy in both healthy subjects and patients with Type 2 diabetes mellitus (T2DM).
Phase Ia Study Results
The Phase Ia trial was a placebo-controlled, single-center study assessing GZR4’s safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy male volunteers. The trial, which employed a dose-escalation design, involved participants receiving either GZR4 at varying doses (1, 3, 6, or 12 nmol/kg), placebo, or an active comparator, insulin degludec (IDeg) at 0.4 U/kg.
Results demonstrated that GZR4 was well-tolerated, with no serious adverse events reported. The glucose-lowering effect of GZR4 was stable for up to one week post-administration. On day 7, the glucose infusion rate (GIR) in participants receiving the highest dose of GZR4 (12 nmol/kg) was approximately 80% of that on day 2, indicating a prolonged effect. Furthermore, the average daily glucose-lowering effect of 6 nmol/kg GZR4 was comparable to that of IDeg, suggesting GZR4’s potency is approximately 2.5 times greater than IDeg based on a similar molar concentration.
Phase Ib Study Results
In the Phase Ib trial, 36 T2DM patients previously treated with basal insulin were randomised to receive GZR4 (6, 8, or 12 nmol/kg) weekly or daily IDeg, for six weeks. The trial found that GZR4 was safe and well-tolerated, with no severe hypoglycaemic events reported. The maximum plasma concentration of GZR4 increased with dosage, with a time to maximum concentration of approximately 32 hours and a half-life of about 135 hours.
The study revealed dose-dependent reductions in fasting blood glucose (FBG) with GZR4, outperforming IDeg. Specifically, FBG reductions in week 6 were -1.77 ± 0.20, -2.03 ± 0.66, and -2.75 ± 0.71 mmol/L for the 6, 8, and 12 nmol/kg GZR4 groups, respectively, compared to -1.12 ± 0.36 mmol/L for IDeg. Additionally, the 6 nmol/kg GZR4 group achieved a reduction in HbA1c of 0.76 ± 0.14%, significantly better than the 0.13 ± 0.21% reduction in the IDeg group.
Future Developments
Gan & Lee Pharmaceuticals is also progressing with a Phase II study, evaluating GZR4 in a broader patient population with inadequate glycemic control on oral antidiabetic drugs. This study, which has enrolled 179 participants, aims to compare the efficacy and safety of GZR4 with daily insulin degludec.
Dr. Gan Zhong-ru, Chairman of Gan & Lee Pharmaceuticals, highlighted the potential benefits of weekly insulin preparations. “GZR4 has shown the ability to provide stable glycemic control for an entire week with a single dose, which could improve adherence and reduce the risk of hypoglycaemia,” he said. The company anticipates further validation of GZR4’s clinical benefits in upcoming trials.
