BEIJING and BRIDGEWATER, N.J., June 23, 2024 /PRNewswire/ — Gan & Lee Pharmaceuticals (Gan & Lee, Shanghai Stock Exchange: 603087) announced the results of the Phase 1b/2a clinical study of the Company’s independently developed glucagon-like peptide-1 (GLP-1) receptor agonist, GZR18 Injection, in an obese/overweight population in China, along with the results of two other innovative insulins’ preclinical studies in poster presentations at the American Diabetes Association’s（ADA’s）84th Scientific Sessions.
This randomized, double-blind, placebo-controlled, dose-escalation Phase 1b/2a clinical study evaluated the safety, tolerability, pharmacokinetics and efficacy of GZR18 Injection in Chinese subjects with obesity/overweight after multiple administration on a once-weekly (QW) or bi-weekly (Q2W) dosing interval. A total of 36 obese participants were enrolled in the study and randomized in a 3:1 ratio to receive a dose titration of 1.5 mg to 30 mg of GZR18 Injection or a matching placebo for a total of 35 weeks.
The study results demonstrated a superior efficacy of GZR18 Injection than placebo for weight reduction in Chinese obese subjects. After 35 weeks of treatment, the mean weight change from baseline in the GZR18 QW group was -16.5 kg (95% CI: -19.9 kg, -13.1 kg); the placebo-adjusted mean percent weight change from baseline was -18.6% (95% CI: -25.5%, -11.6%). Although it was not a head-to-head study, when compared to the published data on weight reduction of similar products currently available on the market, GZR18’s weight-reducing ability outperformed Semaglutide and dual-incretin receptor targeted Tirzepatide in similar study duration. Meanwhile, the mean weight change from baseline in the GZR18 Q2W group was -11.3 kg (95% CI: -15.4 kg, -7.2 kg); the placebo-adjusted mean percent weight change from baseline was -13.5% (95% CI: -21.0%, -6.0%).
In addition, the percentage of participants achieving weight reductions of ≥5%, 10%, and 15% from baseline were 100.0%, 90.0%, and 80.0%, respectively, in the GZR18 QW group, and the percentage of participants achieving weight reductions of ≥5%, 10%, and 15% from baseline were 71.4%, 71.4%, and 42.9%, respectively, in the GZR18 Q2W group. No participant in the placebo group achieved a weight reduction of 5% and above.
In terms of safety, GZR18 Injection was well tolerated in obese participants. The most commonly reported adverse events (AE) during treatment were gastrointestinal related AEs, and all were mild to moderate in severity. This is consistent with the incretin-based therapies approved for the treatment of obesity and overweight and occurred mainly in the early dose-escalation period. There were no serious hypoglycemic events in this study and no serious adverse events related to the investigational drug.
Gan & Lee also announced that a multi-center, placebo-controlled, randomized, double-blind, 30-week Phase 2 clinical study evaluating the efficacy and safety of GZR18 Injection in Chinese adults with obesity and overweight is in progress. A total of 338 adults with obesity or overweight were enrolled in this study, and the study explores a broader dose range and frequency of administration. The main body of the Phase 2 has now been completed, and the priliminary study data further support the results of the reported Phase 1b/2a obese/overweight study, particularly the positive results achieved with bi-weekly dosing frequency.
"We are very excited about the clinical results of the GZR18 program to the present day." Dr. Gan Zhong-ru, Founder of Gan & Lee, commented. "Our unique molecular design delays the onset of drug action and attenuates the peak effect, thereby improving drug tolerability and achieving smooth and sustained weight loss in a stepwise manner. Moreover, GZR18 has a longer duration of action, which is expected to be administered once every two weeks. Meanwhile, we hope that the clinical results of GZR18 will provide more evidence to reveal the mechanism of action of different targets of Incretins and Glucagon."
In addition, Gan & Lee announced the results of preclinical trials of the company’s investigational products: GZR4, a once-weekly insulin analog, and GZR101, a premixed dual insulin analog, at the ADA’s 84th Scientific Sessions:
Once-weekly Insulin Analog GZR4
GZR4 is a novel ultra-long-acting basal insulin analog designed for once-weekly administration. Results from preclinical studies have shown that GZR4 has a significantly higher affinity for human serum albumin (HSA) and a significantly lower affinity for the insulin receptor than insulin Icodec, another once-weekly insulin analog. Moreover, unlike insulin Icodec, GZR4 maintains its activity in activating the insulin receptor after binding to albumin. In the studies using animal models of diabetes, the glucose-lowering effect of GZR4 was observed to be 2-3 times greater than that of insulin Icodec. Based on the preclinical results, GZR4 is expected to be the fourth-generation basal insulin that can be administered once a week to achieve an effective glycemic control.
Premixed Insulin Analog GZR101
GZR101 injection is a premixed insulin analog made from a combination of ultra-long-acting basal insulin GZR33 injection and rapid-acting insulin aspart (Rapilin®). Different from traditional premixed insulin analogs, the duration of glucose-lowering effect of basal insulin component (GZR33) in GZR101 can last 72 hours, and there is no significant peak within 24 hours after reaching a steady state with multiple injections. When combined with insulin aspart (Rapilin®️) to make a premixed insulin analog, it can achieve smooth control of fasting and postprandial blood glucose throughout the day. In diabetic animal models, GZR101 is significantly superior than insulin degludec/insulin aspart (IDegAsp) in blood glucose reduction and safety. As a premixed insulin analog developed based on an advanced concept, GZR101 is expected to make an important contribution to the control of blood glucose and the reduction of the risk of hypoglycemia in patients with diabetes globally.
Conclusions and Future Directions
The ADA’s 84th scientific sessions highlighted Gan & Lee Pharmaceuticals’ leadership in developing next-generation diabetes and obesity treatments. With these latest preclinical and clinical results, the Company will continue to advance the development of innovative therapeutics for diabetes. While ongoing studies and upcoming trials will further support the positive influence of these innovative medicines on public health issues related to diabetes and obesity.
Forward-looking Statements
Forward-looking statements are based on our expectations and assumptions as of the date of the statements. Actual results may differ materially from those expressed in these forward-looking statements due to a variety of factors, and we can give no assurance 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.
References：
American Diabetes Association. https://diabetes.org/ ADA’s 84th Scientific Sessions. https://professional.diabetes.org/scientific-sessions
About Gan & Lee
Gan & Lee Pharmaceuticals developed the first Chinese domestic insulin analog. Currently, Gan & Lee has six core insulin products, including five insulin analog varieties: long-acting glargine injection (Basalin®), fast-acting lispro injection (Prandilin™), fast-acting aspart injection (Rapilin®), mixed protamine zinc lispro injection (25R) (Prandilin™25), aspart 30 injection (Rapilin®30), and one human insulin injection – mixed protamine human insulin injection (30R) (Similin®30). The company has two approved medical devices in China, namely reusable insulin injection pen (GanleePen), and disposable pen needle (GanleeFine®).
In China’s 2024 National Insulin-Specific Centralized Procurement, Gan & Lee Pharmaceuticals ranked second overall and first among domestic companies in terms of procurement demand for insulin analogs. The company is also making strides in international markets, with the disposable pen needle (GanleeFine®) approved by the US Food and Drug Administration (FDA) in 2020 and received GMP inspection approval from the European Medicines Agency (EMA) in 2024. These achievements significantly boost Gan & Lee’s competitiveness in both international and domestic markets.
In the future, Gan & Lee will strive for comprehensive coverage in diabetes treatment. Moving forward with its mission to become a world-class pharmaceutical company, Gan & Lee will also actively develop new chemical entities and biological drugs, focusing on treatments for metabolic diseases, cardiovascular diseases, and other therapeutic areas.
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