- In Phase Ia clinical trials, GZR4 demonstrated a favorable safety and tolerability profile in healthy subjects and maintained stable glucose-lowering effects for up to one week after a single dose.
- In a Phase Ib clinical trial, patients with type 2 diabetes mellitus (T2DM) treated with GZR4 for 6 weeks were safe and well tolerated. GZR4 also demonstrated improvements in fasting plasma glucose (FBG), glycosylated hemoglobin (HbA1c), and time in range (TIR) across all dose groups, with better outcomes than the insulin degludec (IDeg) group.
statement:
1. GZR18 injection is an investigational drug and has not yet been approved.
2. Gan & Lee Pharmaceuticals Use of unapproved agents/indications is not recommended.
Phase Ia study results
This placebo- and active-controlled, single-center, single-dose, randomized, dose-escalation study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GZR4 in healthy adult male participants. The study followed a dose-escalation design, starting with a low dose and gradually increasing to a higher dose. Participants in cohorts 1-4 were randomized to receive subcutaneous injections of GZR4 (1, 3, 6, or 12 nmol/kg) or placebo, and cohort 5 received a single dose of insulin degludec (IDeg) 0.4 U/kg (2.4 nmol/kg) as an active control. Twenty-four-hour glucose clamp measurements were performed on days 2 and 7 after GZR4 administration in cohorts 2-4, respectively, and on day 1 after IDeg administration in cohort 5.
GZR4 was shown to be safe and well tolerated in healthy subjects, with no serious adverse events (SAEs) reported and no discontinuations due to study drug-related adverse events.PD results showed that in subjects receiving 12 nmol/kg GZR4, glucose infusion rate (GIR) on day 7 was approximately 80% of that on day 2. The blood glucose lowering effect of GZR4 has been shown to last for approximately one week. On the other hand, the area under the GIR-time curve on day 2 (AUCGIR, 24-48 hours) and day 7 (AUCGIR, 144-168 hours) at a dose of 6 nmol/kg of GZR4, the 24-hour GIR (AUCGIR, 0-24 hours) with IDeg 0.4 U/kg (2.4 nmol/kg), the mean mean nasogastric …, This suggests that the average daily blood glucose lowering effect of GZR4 is comparable to that of IDeg. Converting accordingly, we estimate that the potency of GZR4 is approximately 2.5-fold higher than IDeg when assessed based on similar molar concentrations.
Phase Ib study results
In this randomized, open-label, active-controlled, multicenter, dose-escalation phase Ib study, 36 patients with type 2 diabetes previously treated with basal insulin were randomized in a 3:1 ratio to receive a fixed dose of GZR4 (6, 8, or 12 nmol/kg) once weekly or once daily (IDeg) (equal to their daily basal insulin dose before enrollment) for 6 weeks.
PK results are based on maximum plasma concentration (Cmaximum) increased dose-dependently, whereas the time to reach the maximum concentration (Tmaximum) and half-lives at steady state were approximately 32 and 135 h, respectively. PD data showed a dose-dependent decrease in FBG at week 6 (-1.77 ± 0.20, -2.03 ± 0.66, and -2.75 ± 0.71 mmol/L in the 6, 8, and 12 nmol/kg groups, respectively). The results were better than those of the IDeg group (-1.12 ± 0.36 mmol/L). After 6 weeks of treatment, HbA1c decreased by 0.76 ± 0.14% in the 6 nmol/kg GZR4 group compared with 0.13 ± 0.21% in the IDeg group.
GZR4 demonstrated a good safety and tolerability profile in patients with type 2 diabetes. No serious adverse events were reported in any treatment group. The most frequently reported adverse event during treatment was hypoglycemia, but no severe hypoglycemia occurred.
TDetailed results from the Phase I study will be published in a peer-reviewed journal.
Study data are presented as mean ± standard error.
Gan & Lee Pharmaceuticals The company also announced an ongoing multicenter, randomized, open-label, parallel-controlled, target-treatment Phase 2 study in patients with type 2 diabetes inadequately controlled with oral antidiabetic medications, including insulin-naive and basal insulin-treated patients. The study will enroll 179 adults and compare the efficacy and safety of once-weekly GZR4 versus once-daily insulin degludec. All participants have completed treatment, and preliminary results are encouraging, further supporting the findings of the Phase 1 study.
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About Gan & Lee
Gan Li Pharmaceutical developed China’s first domestic insulin analogue. Currently, Gan Li has six main insulin products, five of which are long-acting insulin glargine injections (Basaline). ®), immediate-release lispro injection (Prandilin™), Rapid-acting Aspart Injection (Lapirin ®), Mixed Protamine Zinc Lispro Injection (25R) (Prandiline™25), Aspart 30 Injection (Lapirin ®30), and one bottle of human insulin injection – Mixed Protamine Human Insulin Injection (30R) (Similin ®30) The company has two approved medical devices.
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Going forward, Gan & Lee will pursue its mission of becoming a world-class pharmaceutical company with comprehensive coverage of diabetes treatment, focusing on the treatment of metabolic diseases, cardiovascular diseases and other therapeutic areas, and will also actively engage in the development of new chemical entities and biological medicines.
Forward-Looking Statements
Forward-looking statements are based on our expectations and assumptions as of the date they are made. Actual results may differ materially from those indicated in these forward-looking statements due to a variety of factors, and we cannot guarantee that such results will be achieved in the future. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
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