Insulin aspart

北京和新泽西州布里奇沃特 2024年6月24日 /美通社/ -- 甘李药业股份有限公司（以下简称：甘李药业，股票代码：603087.SH）宣布，公司自主研发的胰高血糖素样肽-1（glucagon-like peptide-1, GLP-1）受体激动剂GZR18注射液在中国肥胖/超重人群中的Ib/IIa期临床研究结果和其他两项胰岛素新药临床前研究结果在2024年美国糖尿病协会第84届科学会议上以壁报的形式展示。 此次披露的GZR18临床研究是一项在中国肥胖/超重患者中开展的随机、双盲、安慰剂对照的多次剂量递增研究，该研究主要评估受试者接受每周（QW）或每两周（Q2W）一次GZR18注射液治疗后的安全性、耐受性、药代动力学和有效性。该研究总共入组36名肥胖受试者，按3:1的比例随机接受1.5 mg至30 mg的GZR18注射液或安慰剂的剂量滴定治疗，总治疗周数35周。 研究结果显示，GZR18注射液在中国肥胖受试者中的减重疗效优于安慰剂。治疗35周后，GZR18 QW组体重较基线的平均变化差值为-16.5 kg（95%CI：-19.9 kg, -13.1 kg）；体重与安慰剂组的差值达-18.6%（95%CI：-25.5%, -11.6%）。虽然不是头对头的研究，但与已上市同类产品公布的减重数据相比， GZR18在相似给药周期中的减重效果优于司美格鲁肽和双靶点的替尔泊肽。 同时，GZR18 Q2W组体重较基线的平均变化差值为-11.3 kg（95%CI：-15.4 kg, -7.2 kg）；与安慰剂组的平均变化差值达-13.5%（95%CI：-21.0%, -6.0%）。 此外，GZR18 QW组体重较基线降低≥5%、10%、15%的受试者比例分别为100.0%、90.0%和80.0%；GZR18 Q2W组体重较基线降低≥5%、10%、15%的受试者比例分别为71.4%、71.4%和42.9%，而安慰剂组无受试者体重降幅达到5%及以上。 安全性方面，GZR18注射液在肥胖受试者中表现出良好的耐受性。在治疗期间最常报告的不良事件（AE）为胃肠道相关不良事件，且全部为轻、中度。这与GLP-1类药物的常见反应一致，且主要发生在剂量递增早期。本研究未发生严重低血糖事件，未发生与试验用药品有关的严重不良事件。 甘李药业同时宣布，一项在中国成年肥胖/超重受试者中评价GZR18注射液疗效和安全性的多中心、安慰剂对照，随机，双盲，30周的Ⅱ期临床研究正在进行中。该研究入组338名超重或肥胖成年人，探索更宽的剂量范围和给药频率。目前，该研究所有受试者均已出组，初步研究数据进一步验证了Ib/IIa的研究结果，特别是双周给药取得了积极的效果。 “我们对 GZR18项目迄今为止的临床结果感到非常兴奋。”甘李药业董事长甘忠如博士表示，“我们独特的分子设计能够延缓药物起效时间，减弱峰值效应，从而提高药物耐受性，达到平稳且持续渐进减轻体重的效果。并且GZR18作用时间更长，可每两周给药一次。同时，我们希望GZR18的临床结果能为揭示不同靶点的肠促胰素（Incretins）、胰高血糖素（Glucagon）等的作用机理提供更多的证据支持。” 此外，甘李药业还于本届ADA科学会议中公布了公司在研新药胰岛素周制剂GZR4和双胰岛素复方制剂GZR101的临床前试验结果： 胰岛素周制剂 GZR4 GZR4是一款新型超长效基础胰岛素类似物，设计为每周一次给药。临床前研究结果表明，与另一种胰岛素周制剂Icodec相比，GZR4与人血清白蛋白（HSA）亲和力显著增加，胰岛素受体亲和力明显降低。而且，与Icodec不同，GZR4在和白蛋白结合形成复合体后，依然能够保持激活胰岛素受体的活性。在糖尿病动物模型的研究中，GZR4的降糖效果是Icodec的2-3倍。GZR4有望成为每周仅需给药一次的第四代基础胰岛素。 双胰岛素复方制剂 GZR101 GZR101是甘李药业自主研发的一种新型双胰岛素复方制剂，由长效胰岛素GZR33和速效胰岛素门冬胰岛素组成。与传统的预混胰岛素制剂不同，GZR101中基础胰岛素组分（GZR33）的降糖作用持续时间可达72小时，经多次注射达到稳态后，24小时无明显峰值。与门冬胰岛素（锐秀霖 ®️ ）制成双胰岛素制剂后，可实现全天空腹与餐后血糖的平稳控制。在糖尿病动物模型中，GZR101在降低血糖和安全性方面均显著优于德谷门冬双胰岛素制剂。作为一种根据新理念研制成的胰岛素复合制剂，GZR101有望为全球糖尿病患者血糖达标，降低低血糖风险做出重要贡献。 结论与未来方向 本届ADA会议突显了甘李药业在开发新一代糖尿病和肥胖治疗方法方面的领先地位。凭借最新的临床成果，公司将进一步推动糖尿病创新治疗药物的研发。正在进行的研究和即将开始的试验将进一步验证这些创新药物对糖尿病和肥胖相关公共健康问题产生的积极影响。 参考文献: 1. American Diabetes Association. https://diabetes.org/ 2. ADA's 84th Scientific Sessions. https://professional.diabetes.org/scientific-sessions 前瞻性声明： 该前瞻性陈述基于我们在陈述之日的预期和假设。由于各种因素，实际结果可能与这些前瞻性陈述中表达的内容存在重大差异，我们不能保证将来会实现这些结果。我们不承担更新或修改任何前瞻性陈述的义务，无论是由于新信息、未来事件或其他原因。 关于甘李药业 甘李药业股份有限公司（简称：甘李药业，股票代码：603087.SH）作为中国第一家掌握产业化生产重组胰岛素类似物技术的高科技生物制药企业，具备完整胰岛素研发管线。目前，公司拥有六款核心胰岛素产品，包括五个胰岛素类似物品种：长效甘精胰岛素注射液（长秀霖 ® ）、速效赖脯胰岛素注射液（速秀霖 ® ）、门冬胰岛素注射液（锐秀霖 ® ）、预混精蛋白锌重组赖脯胰岛素混合注射液（25R）（速秀霖 ® 25）、门冬胰岛素30注射液（锐秀霖 ® 30）；以及人胰岛素品种：预混精蛋白人胰岛素混合注射液（30R）（普秀霖 ® 30），产品覆盖长效、速效、预混三个胰岛素功能细分市场。同时，公司产品覆盖相关医疗器械，包括可重复使用的胰岛素注射笔（秀霖笔 ® ）和一次性注射笔用针头（秀霖针 ® ）。 在 2024 年中国胰岛素接续采购中，甘李药业的胰岛素类似物采购需求在所有中选企业中排名第二，在国内企业中排名第一。公司的国际化进程也在不断推进，一次性笔形针（GanleeFine ® ）在2020年获得美国食品药品管理局（FDA）批准。同时，2024年公司通过了欧洲药品管理局（EMA）的 GMP 检查。这标志着公司在国际和国内市场上的竞争力得到大幅提升。 未来，甘李将努力实现糖尿病治疗领域的全面覆盖，进一步提升公司在糖尿病治疗领域的市场竞争力。公司还将积极开发新的化学药和生物新药，重点关注代谢性疾病、心血管疾病和其他治疗领域。 联系方式： BPRD@ganlee.com (Media) BD@ganlee.com (Business Development)

BEIJING and BRIDGEWATER, N.J., June 22, 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. ADA's 84th 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. Further Information: [email protected] (Media) [email protected] (Business Development) SOURCE Gan & Lee Pharmaceuticals