A Study to Evaluate the Efficacy and Safety of Once-weekly Insulin Icodec when Switching from Daily Basal Insulins Compared to Once-daily Insulin Glargine U100 in Adults with Type 2 Diabetes

开始日期2024-06-20

申办/合作机构

Novo Nordisk India Pvt Ltd.

CTIS2023-506084-34-00 / Recruiting

A Study to Evaluate the Efficacy and Safety of Once-weekly Insulin Icodec when Switching from Daily Basal Insulins Compared to Once-daily Insulin Glargine U100 in Adults with Type 2 Diabetes - NN1436-7724

开始日期2024-04-19

申办/合作机构

Novo Nordisk A/S

NCT06340854 / Recruiting临床3期

A Study to Evaluate the Efficacy and Safety of Once-weekly Insulin Icodec When Switching From Daily Basal Insulins Compared to Once-daily Insulin Glargine U100 in Adults With Type 2 Diabetes

This study compares insulin icodec, a new insulin taken once a week, to insulin glargine, an insulin taken once a day. The study medicine will be investigated in participants with type 2 diabetes. Participants will either get insulin icodec or insulin glargine. Which treatment participants get is decided by chance. Insulin icodec is the new medicine being tested, while insulin glargine is already approved and can be prescribed by doctors. Participants will get one injection of insulin icodec once a week, or one injection of insulin glargine once a day, depending on the treatment group participants are assigned into. Participants will use a pen with a small needle to inject the medicine under participants skin into participants thigh, upper arm or stomach.The study will last for about 9 months, but participants will only be taking the study medicine for 6 months.

开始日期2024-04-19

申办/合作机构

Novo Nordisk A/S

100 项与依柯胰岛素相关的临床结果

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100 项与依柯胰岛素相关的转化医学

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100 项与依柯胰岛素相关的专利（医药）

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项与依柯胰岛素相关的文献（医药）

2024-11-01·Lancet Diabetes & Endocrinology

Continuous glucose monitoring-based metrics and the duration of hypoglycaemia events with once-weekly insulin icodec versus once-daily insulin glargine U100 in insulin-naive type 2 diabetes: an exploratory analysis of ONWARDS 1

Article

作者: Ásbjörnsdóttir, Björg ; Lingvay, Ildiko ; Bergenstal, Richard M ; Mader, Julia K ; Nishida, Tomoyuki ; Watt, Sara K ; Rosenstock, Julio

BACKGROUND:

Continuous glucose monitoring (CGM) can provide a comprehensive assessment of glycaemic control. This exploratory analysis of the ONWARDS 1 trial assessed CGM-based metrics and CGM-derived hypoglycaemia duration in insulin-naive individuals with type 2 diabetes treated with subcutaneous once-weekly insulin icodec (icodec) versus once-daily insulin glargine U100 (glargine U100).

METHODS:

ONWARDS 1 was a 78-week (52-week main treatment phase and a 26-week treatment extension phase plus a 5-week follow-up), randomised, open-label, treat-to-target, phase 3a trial done at 143 sites (outpatient clinics and hospital departments) across 12 countries. Adults (aged ≥18 years) with type 2 diabetes (HbA_1c: 7·0-11·0%) who had not previously received insulin were randomly assigned (1:1) via an interactive web-response system to once-weekly icodec or once-daily glargine U100. Double-masked CGM data were collected during treatment initiation (weeks 0-4), midtrial (weeks 22-26), end of main phase (weeks 48-52), end of extension phase (weeks 74-78), and follow-up (weeks 78-83). Secondary and exploratory outcomes were CGM-based metrics, including the mean percentages of time in glycaemic range (TIR; sensor glucose 3·9-10·0 mmol/L [70-180 mg/dL]), time in tight range (TITR; 3·9-7·8 mmol/L [70-140 mg/dL]), time above range (TAR; >10·0 mmol/L [>180 mg/dL]), and time below range (TBR; <3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]), and CGM-derived hypoglycaemic episode durations (episodes defined by sensor glucose <3·9 mmol/L [<70 mg/dL for ≥15 consecutive minutes]). Analyses were done in the full analysis set (all randomly assigned participants). The ONWARDS 1 trial is registered with ClinicalTrials.gov, NCT04460885, and is complete.

FINDINGS:

Participants were enrolled and randomly assigned in ONWARDS 1 between Nov 25, 2020, and Dec 1, 2022 (n=492 in each treatment group). During treatment initiation, we observed no statistically significant differences in the mean percentages of TIR, TITR, TAR, and TBR with icodec versus glargine U100. During the midtrial, end of main phase, and end of extension phase periods, the mean percentages of TIR and TITR were statistically significantly greater and the mean percentages of TAR statistically significantly lower with icodec versus glargine U100. The mean percentages of TIR met the internationally recommended CGM target (>70%) with icodec but not with glargine U100 during the three periods. TBR (<3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]) was low and below recommended targets (<4% and <1%, respectively) across all study periods in both treatment groups, with no statistically significant differences between treatment groups for the lower threshold (<3·0 mmol/L [<54 mg/dL]). During the follow-up period, mean percentages of TIR, TITR, TAR, and TBR did not statistically significantly differ with icodec versus glargine U100. The duration of overall hypoglycaemic episodes was similar between treatment groups throughout the trial (median duration ≤35 min).

INTERPRETATION:

These CGM data support the long-term efficacy and safety of icodec versus glargine U100 during treatment and indicated no increase in the duration of individual hypoglycaemic episodes with icodec versus glargine U100 in insulin-naive individuals with type 2 diabetes.

FUNDING:

Novo Nordisk.

2024-11-01·DIABETES RESEARCH AND CLINICAL PRACTICE

Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes: An analysis of patient-reported outcomes and participant interviews from ONWARDS 2 and 5 and a physician survey from ONWARDS 1

Article

作者: Meller Donatsky, Anders ; Benamar, Malik ; Philis-Tsimikas, Athena ; Goldenberg, Ronald ; Franek, Edward ; Davies, Melanie ; Polonsky, William ; Carstensen, Lisbeth ; Kellerer, Monika

AIMS:

The ONWARDS phase 3a clinical trials evaluated once-weekly insulin icodec (icodec) versus once-daily basal insulin in type 2 diabetes. This analysis investigated the treatment-related experiences of participants from ONWARDS 5 and 2, and physicians from ONWARDS 1.

METHODS:

Patient-reported outcomes were only collected during ONWARDS 5 (icodec with a dosing guide app vs. once-daily basal analogues) and 2 (icodec vs. once-daily insulin degludec). ONWARDS 1 (icodec vs. once-daily insulin glargine U100) physicians' treatment preferences and satisfaction were obtained via an online survey.

RESULTS:

In ONWARDS 5 and 2, there was a statistically significantly greater increase in total treatment satisfaction from baseline to end of treatment for icodec/icodec with app versus once-daily comparators, mostly driven by participants' willingness to continue and recommend treatment. In ONWARDS 2, 93.7 % of icodec users preferred once-weekly over once-daily basal insulin, mainly owing to less frequent injections and ease of use. ONWARDS 1 physicians reported greater satisfaction with once-weekly than with once-daily basal insulin and were more likely to recommend once-weekly injections.

CONCLUSIONS:

These results demonstrate improved treatment satisfaction with, and strong preferences for, once-weekly versus once-daily basal insulin. Treatment convenience and willingness to continue and recommend once-weekly basal insulin treatment were highlighted.

CLINICAL TRIAL REGISTRATIONS:

ONWARDS 1: NCT04460885; ONWARDS 2: NCT04770532; ONWARDS 5: NCT04760626.

2024-10-01·DIABETIC MEDICINE

Insulin icodec: A novel once‐weekly treatment for diabetes

Review

作者: Gore, Ashwini ; Deeb, Alexander ; Schaffner, Hannah ; Genovese, Ariana ; Sheikh‐Ali, Mae ; Sutton, David ; Goldfaden, Rebecca ; Wiener, Jordyn ; Berner, Jason ; Huston, Jessica ; DeLuca, Amanda ; Deeb, Wasim

Abstract:

Aims:

To summarize the results of clinical studies of insulin icodec, an investigational insulin analog designed for once‐weekly administration, in adults with type 1 and type 2 diabetes.

Methods:

Thirteen published articles describing clinical studies of insulin icodec were identified in PubMed, and data pertinent to key study outcomes were selected for inclusion in this review.

Results:

In insulin‐naïve and insulin‐treated individuals, icodec demonstrated efficacy in glycaemic control superior or noninferior to that of insulins glargine U100, glargine U300 and degludec. Icodec exhibited a safety profile comparable to marketed insulins, with the exception of hypoglycaemic event rates.

Conclusions:

As a once‐weekly alternative to daily basal insulin, icodec is expected to improve patient adherence and satisfaction, reducing the required number of injections per year from 365 to 52 and providing a dosing option potentially attractive to a wide range of insulin users. However, clinical data suggest a notable risk of hypoglycaemia with weekly icodec administration, especially in individuals with type 1 diabetes.

162

项与依柯胰岛素相关的新闻（医药）

2024-11-03

·GoDesign

诺和诺德 | 缓释低血糖的葡萄糖敏感型胰岛素

低血糖（hypoglycaemia）的发生一直是糖尿病在胰岛素治疗过程中的主要挑战，胰岛素剂量必须谨慎调整以确保血糖值维持在正常范围。但是将胰岛素剂量与波动的血糖值进行合理地匹配是较困难的，轻微的胰岛素过量很容易导致低血糖的发生。根据血糖值的变化自动地（auto-adjust）调节自身生物活性的新胰岛素，可以更好地实现血糖的控制避免低血糖的发生。2024年10月，诺和诺德公司在Nature发表题为"Glucose-sensitive insulin with attenuation of hypoglycaemia"的研究论文 [1]，设计发现了新胰岛素NNC2215，可以根据糖尿病人的血糖范围作出可逆地动态地响应。 ——生物学背景—— 从1922年人类第一次发现使用胰岛素，到1982年首次作为临床药物批准使用，再到近几十年以诺和诺德公司为代表的各种胰岛素类药物推陈出新 [2]，胰岛素的结构修饰与功能也是不断地锦上添花。2015年批准使用的德谷胰岛素（Degludec）在体内持续作用时间超过42 h，2021年研究发现的口服胰岛素Icodec 在人体内半衰期达到196 h [3]，目前已经处于临床三期试验中 [4]。然而通过胰岛素来解决糖尿病人血糖的问题目前存在低血糖的风险，血糖的波动受很多因素的影响而难以实时预测，包括三餐的时机和性状，锻炼情况，健康或生病状况，胰岛素的敏感性等。图0：胰岛素类药物的结构及发展 [2] ——核心内容—— 这篇文章描述了动态调节血糖的NNC2215的分子设计：是将胰岛素连上一个葡萄糖开关Switch，分别在B1Phe的N端通过短linker以O1糖苷键连有葡萄糖分子，以及B29Lys侧链上安装容纳结合葡萄糖的大环（图2a）。当葡萄糖浓度升高时，游离态的葡萄糖竞争性结合在大环上，使得NNC2215为打开状态（也就是正常状态的胰岛素构象），对胰岛素受体的亲和力较高；当葡萄糖浓度降低时，NNC2215转为关闭状态（此时扭曲拧紧了胰岛素构象）减弱了对胰岛素受体的结合能力，进而减缓了细胞对葡萄糖的摄取，避免了低血糖的发生。（图1a）当血糖浓度从0-20 mM升高时，NNC2215对胰岛素受体的亲和能力提高了12.5倍，当血糖浓度从3-20 mM升高时，NNC2215对胰岛素受体的亲和能力提高了3.2倍。图1：a. NNC2215的作用机制；b. 基于PDB 6PXV搭建的结构模型图2a展示了NNC2215的结构，O1糖苷键连接的葡萄糖分子以及Click反应连接的大环。对照分子NNC2215a仅连接大环，不连接糖。图2b通过ITC实验测得大环对葡萄糖的结合解离常数为98 μM。图2c通过Native MS测得NNC2215和NNC2215a对葡萄糖的结合解离常数分别为2.1 mM和0.5 mM。图2：a. NNC2215的结构；b.c. ITC和MS测定Kd 接着在体外实验测定了NNC2215、insulin、Degludec在不同浓度的葡萄糖下对人胰岛素受体（human insulin receptor A，hIR-A）的结合水平变化。可以看到相较于其它胰岛素，NNC2215随着葡萄糖浓度的升高，对胰岛素受体的结合能力显著增强。（图3）图3：不同葡萄糖浓度下各类胰岛素对其受体的结合能力测定 L型葡萄糖（非天然）较难被代谢，但是可以结合到NNC2215的大环中，以L-葡萄糖作为工具探究动物体内NNC2215对血糖的影响。随着L型葡萄糖浓度增加，NNC2215对大鼠体内葡萄糖（D型葡萄糖）浓度下调能力显著增强。（图4a.b.）随后在猪模型上研究两种胰岛素对葡萄糖的敏感性，在暂停摄入葡萄糖后，相比于Degludec，NNC2215对葡萄糖下调的速度也在减缓。这证明了其生物活性，可以避免低血糖的发生。图4：a.b. 大鼠模型中NNC2215对血糖的动态调节；c. 在LYD猪模型上研究葡萄糖暂停和重启过程中胰岛素的血糖调节影响；d. Pharmacokinetic/pharmacodynamic模建结果 ——小结—— 全文总结，诺和诺德公司通过在胰岛素上引入开关Switch得到的胰岛素衍生物NNC2215，具有随血糖变化动态调节其结合胰岛素受体的能力，该设计可以显著降低传统胰岛素给药后出现低血糖的风险，快速地满足三餐期间血糖波动时对胰岛素更高功能的需求。参考文献： [1] Hoeg-Jensen, T., Kruse, T., Brand, C.L. et al. Glucose-sensitive insulin with attenuation of hypoglycaemia. Nature 634, 944–951 (2024). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41586-024-08042-3 [2] Muttenthaler, M., King, G.F., Adams, D.J. et al. Trends in peptide drug discovery. Nat Rev Drug Discov 20, 309–325 (2021). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41573-020-00135-8 [3] Kjeldsen, Thomas B et al. “Engineering of Orally Available, Ultralong-Acting Insulin Analogues: Discovery of OI338 and OI320.” Journal of medicinal chemistry. 64,1 (2021): 616-628. doi:10.1021/acs.jmedchem.0c01576 [4] Kjeldsen, Thomas B et al. “Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans.” Journal of medicinal chemistry. 64,13 (2021): 8942-8950. doi:10.1021/acs.jmedchem.1c00257 作者：程北溟审稿：任宇浩编辑：王宇哲 GoDesign ID：Molecular_Design_Lab （扫描下方二维码可以订阅哦！）

临床结果

2024-10-31

·Insight数据库

胰岛素双雄逆风翻盘，多线作战、争夺全球市场

一场精彩的重生大戏，正在胰岛素市场上演。近日，两大国产胰岛素龙头亮出了 2024 年三季报成绩单：已走出集采阴霾的甘李药业，保持了稳健增长；通化东宝也成功驶出亏损的漩涡，实现净利润扭亏为盈。而且，随着国内企业不断蚕食外资巨头的份额，市场竞争版图已经发生深刻变化。值得注意的是，胰岛素双雄的征程才刚刚开始，故事线仍在不断延伸。逆风翻盘曾几何时，集采的重压如同乌云蔽日，让众多胰岛素企业陷入阴霾。如今，胰岛素龙头已拨云见日，走出了集采的阴影。甘李药业在 2023 年率先跳出了亏损的泥沼，2024 年增长势头有增无减，前三季度实现总营收达 22.45 亿元，同比增长 17.81%，归母净利润更是同比大幅增长 90.36% 至 5.07 亿元。细观季度数据，甘李药业的稳健增长轨迹清晰可见：2024Q1、Q2、Q3 分别实现归母净利润为 9600.43 万元、2.03 亿元、2.08 亿元，同比增长 95.04%、138.9%、57.47%，正在以肉眼可见的速度快速增长。归其原因，这主要得益于甘李药业在胰岛素集采中以大幅降价扩大了市场份额，比如 2021 年的胰岛素专项集采，6 个竞标产品全部中标（其中有 3 个产品以最低价中标）。之后，借助集采价格优势和近万家新准入医院的机遇，甘李药业快速扩张团队，不仅保证了原有市场稳定增长，还加大了对基层市场的渗透率，2023 年实现国内销售收入 21.82 亿元，同比增长 51.93%。尤其在新一轮全国集采（胰岛素专项接续）中，甘李药业所有 6 款产品均以涨价中标，而产品价格上涨带来的收入增长效应在第三季度初步部分体现，单季实现国内收入 6.8 亿元，同比增长 22.25%。更重要的是，由于甘李药业早在 2005 年起就布局全球市场，特别是新兴市场拓展成效显著，助推公司 2023 年、2024 年前三季度分别实现国际销售收入 3.27 亿元、2.42 亿元，同比增长 131.78%、37.63%。营业收入分地区情况图片来源：甘李药业财报继甘李药业后，通化东宝也成功驶出亏损的漩涡，从困境中破茧而出。 2024 年第三季度，通化东宝实现总营收 7.08 亿元，基本恢复至去年同期水平；尤其是归母净利润、扣非归母净利润分别为 1.64 亿元、1.48 亿元，两项利润指标均扭亏为盈。这归功于通化东宝在今年 4 月的胰岛素专项接续中所有产品均以 A 类/A1 类成功中选，其中有两款三代胰岛素均以 A1 类中标。根据集采续约规则，A1 中选产品可 100% 获得产品首年采购需求量，其余 A 类中选产品的比例为 80%。随着本次集采在第二、三季度陆续执行，第三季度公司胰岛素类似物销量实现翻倍，其中，门冬系列胰岛素销量同比大幅增长近 400%；胰岛素类似物收入占总收入比例已提升至 30% 以上。此外，通化东宝还有多款新品持续放量、贡献业绩增量，包括 GLP-1RA 利拉鲁肽注射液、SGLT-2 产品恩格列净片、DPP-4 产品磷酸西格列汀片。更重要的是，伴随两大龙头走出集采阴影，国内胰岛素市场版图也发生了深刻变化。国产、外资「龙争虎斗」集采既是市场的严酷考验，也是国产替代的催化剂，重新划分了外资企业在胰岛素市场的版图。全国胰岛素集采续约便是这一变化的直观反映。根据全国胰岛素专项集采结果显示，国产胰岛素的市场份额有了显著提升：相较 2021 年胰岛素专项集采，国产份额从 31% 提升到了 45%，进口品牌从 69% 减少至 55%。具体来看，国产二代胰岛素的销量占比从 66% 跃升至 84%，三代胰岛素从 38% 增长至 55%。尤其胰岛素龙头国产替代进程加速明显，其中通化东宝的二代胰岛素市场份额从 35% 增加至 46%，三代胰岛素从 1% 跃升至 9%；甘李药业的二代胰岛素市场份额保持不变，三代胰岛素从 21% 提升至 27%。进口胰岛素的市场份额则出现了显著下降。其中，诺和诺德的二代胰岛素市场份额从 26% 降至 13%，三代胰岛素从 42% 降至 30%；礼来的二代胰岛素市场份额从 8% 降至 3%，三代胰岛素更是从 19% 降至 2%。 2024 年胰岛素续约集采相比 2021 年集采企业需求量占比变化（%）数据来源：上海阳光医药采购网，东方证券研究所当然，国产胰岛素龙头并不满足于现有的市场份额，故事线仍在不断延伸。迭代下一代产品便是其中一条支线。毕竟，诺和诺德、礼来、赛诺菲均已在欧美市场获批了具有革命性意义的四代胰岛素。而且，今年 6 月，诺和诺德研发的全球首个胰岛素周制剂依柯胰岛素注射液（诺和期）在中国上市，用于治疗成人 2 型糖尿病，开启了胰岛素治疗周制剂时代。国产胰岛素龙头自然不甘落后，甘李药业布局了有望成为更优第四代胰岛素周制剂 GZR4（已处于 II 期临床），以及第四代新型预混双胰岛素复方制剂 GZR101 注射液。据临床前研究显示，同等剂量下的 GZR4 降糖效果要优于同类药物诺和期。目前，GZR101 头对头德谷门冬双胰岛素注射液的临床试验已处于 II 期阶段。此外，联邦制药的德谷胰岛素已处于 III 期临床，并且还布局了德谷门冬双胰岛素混合注射液，以及 I 类新药超长效胰岛素周制剂。除了布局下一代产品，国产胰岛素龙头还将在国际化市场和 GLP-1 赛道上，与外资巨头展开更为激烈的角逐。胰岛素双雄「多线作战」海外市场和大热的 GLP-1 类药物，已成为国产胰岛素双雄的增长新逻辑。尤其是甘李药业，已经尝到了全球市场业绩增长带来的甜头，有效缓解了集采所带来的市场压力。现阶段，甘李药业的国际化战略十分明确：一边加速推进研发项目、占领注册标准高地；一边同步开拓全球市场，与山德士就 3 款生物类似药签订商业和供货协议，抢占欧美等发达国家市场，同时积极将优势资源导入新兴国家市场。目前，甘李药业的甘精、赖脯和门冬胰岛素注射液 3 款生物类似药的上市申请，均已获得美国 FDA 和欧盟 EMA 受理。通化东宝也在积极开拓全球市场，其中人胰岛素注射液的上市许可申请已获得欧盟受理，有望贡献显著业绩增量。不仅如此，通化东宝还与健友股份签订了关于甘精、门冬、赖脯三种胰岛素注射液在美国市场的战略合作协议，共同开展上述三种胰岛素产品的开发和生产，同时健友股份将获得产品上市后在美国市场的独家商业化权益。此外，通化东宝还与科兴制药达成合作，在海外 17 个新兴市场加速推动 GLP-1RA 利拉鲁肽注射液的注册和申报进程。甘李药业和通化东宝欧美胰岛素研发和申报情况数据来源：公司公告，东方证券研究所胰岛素双雄的另一条支线任务，就是加速研发 GLP-1 类药物。 GLP-1 类产品以其显著的降糖和减重效果成为了热门靶点，但由于赛道拥挤、竞争激烈，充满了挑战。毕竟，前有礼来、诺和诺德，后有恒瑞医药、华东医药等竞争对手。目前，通化东宝构建了多层次、多样化的 GLP-1 产品梯队，其中利拉鲁肽注射液已在国内获批上市治疗糖尿病、口服小分子 GLP-1 受体激动剂（THDBH110 胶囊）处于 I 期临床、GLP-1/GIP 双靶点受体激动剂（注射用 THDBH120）针对糖尿病和减重适应症均已处于 Ib 期临床，引进的长效 GLP-1 产品司美格鲁肽注射液（针对糖尿病）已处于 III 期临床。甘李药业求精不求多，布局了 2 款差异化的 GLP-1 受体激动剂，其中 GZR18 注射液在 IIb 期试验中显示出每两周给药一次可减重 17.29%（治疗 30 周），有望成为全球首款 GLP-1RA 双周制剂，并已在美国完成了 2 型糖尿病的 I 期试验；创新型口服 GLP-1RA 制剂 GZR18 片，正在中国开展治疗 2 型糖尿病的 I 期临床，目前全球范围内仅有一款口服 GLP-1RA 上市。值得一提的是，甘李药业是首个选择与司美格鲁肽注射液进行头对头评估药物有效性的国产单靶点 GLP-1RA 的企业，目前正在开展 GZR18 头对头司美格鲁肽用于 2 型糖尿病的 IIb 期临床试验。结语国产胰岛素巨头的征途，犹如凤凰涅槃的重生之旅。在集采的洗礼下，甘李药业与通化东宝不仅成功适应了瞬息万变的市场环境，更在逆境中实现蜕变、完成了自我价值的重塑。如今，胰岛素双雄的故事仍在继续，与外资巨头展开多线作战、争夺全球市场的制高点。这一切似乎充满了遐想与期待。参考资料： 1. 各家公司的财报、公告、官微 2.《医药健康行业动态点评：胰岛素续约降幅温和，国产替代加速》，华泰证券 3. 东方证券研报封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

财报带量采购医药出海核酸药物

2024-10-29

·EndPoints

Following March inspection, Novo Nordisk's semaglutide manufacturing facility cited by FDA

The FDA on Tuesday released an inspection report sent to Novo Nordisk earlier this year citing quality-related issues at a site in Kalundborg, Denmark, that manufactures its blockbuster semaglutide drugs and its long-acting insulin. The heavily redacted Form 483 includes eight observations related to the site’s quality, following a seven-day FDA inspection in March. Among the observations are ones related to adequately describing critical process parameters and in-process controls for drug substance manufacturing and processing unit operations. “Master production and control records lack complete manufacturing and control instructions,” the 483 said. The agency also noted that the responsibilities and procedures applicable to the site’s quality control unit “are not fully followed,” and that lab controls at the facility “do not include the establishment of scientifically sound and appropriate sampling plans designed to assure that production cultures conform to appropriate standards of identity, strength, quality, and purity.” “This is the manufacturing process we referred to when we received the CRL for Awiqli from the FDA in July,” a Novo spokesperson told Endpoints News in an email. “We continue to be in contact with the FDA and do not expect to resolve as related to Awiqli this year.” The FDA in July issued a complete response letter to Awiqli, which is approved in the EU, Canada and other markets. At that time, the regulator requested more information relating to the manufacturing process. The company said last November that it would invest more than DKK 42 billion (about $6 billion) to expand existing manufacturing facilities in Denmark, including the Kalundborg site, mainly to increase its capacity for active pharmaceutical ingredients. Back in August, nearly all versions of Novo’s GLP-1 drugs — Wegovy and Ozempic — were taken off the FDA shortage list, and the company reported that prescriptions had doubled in the US since the beginning of the year. “We’re scaling our supply and now we’re serving twice as many people with Wegovy today compared to just at the beginning of the year and we continue to scale,” CEO Lars Fruergaard Jørgensen said at the time.

上市批准

100 项与依柯胰岛素相关的药物交易

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研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
糖尿病	欧盟	Novo Nordisk A/S	2024-05-17
糖尿病	冰岛	Novo Nordisk A/S	2024-05-17
糖尿病	列支敦士登	Novo Nordisk A/S	2024-05-17
糖尿病	挪威	Novo Nordisk A/S	2024-05-17
1型糖尿病	加拿大	Novo Nordisk Canada, Inc.	2024-03-12
2型糖尿病	加拿大	Novo Nordisk Canada, Inc.	2024-03-12

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04880850 \| NCT04770532 (ONWARDS 4 \| ONWARDS 2, EASD2023)	临床3期	2型糖尿病	-	Once-weekly icodec	網憲鹹壓壓顧遞簾選襯(獵淵襯選構醖繭膚齋鬱) = 齋獵淵壓蓋餘壓製願範膚積製獵憲齋鏇願選製 (築艱簾齋顧積蓋齋鏇觸 )	积极	2023-10-04
				Once-daily degludec	網憲鹹壓壓顧遞簾選襯(獵淵襯選構醖繭膚齋鬱) = 艱餘糧簾夢網窪鑰選鏇膚積製獵憲齋鏇願選製 (築艱簾齋顧積蓋齋鏇觸 )
NCT04760626 (ONWARDS 5, EASD2023)	临床3期	2型糖尿病	-	Once-weekly insulin icodec with a dosing guide app	憲夢襯窪遞選遞鏇齋遞(鬱顧獵襯蓋鹹蓋衊鹹壓): P-Value = <0.0001 更多	积极	2023-10-03
				Once-daily basal insulin analogues (degludec, glargine U100 or glargine U300)
NCT04880850 \| NCT04770532 \| NCT04460885 \| NCT04848480 \| NCT04795531 \| NCT04760626 (ONWARDS 1-6, EASD2023)	临床3期	-	-	Once-weekly insulin icodec	築遞顧襯憲膚願顧製蓋(觸壓觸窪鹽簾廠衊壓鬱) = 顧範餘製衊觸築壓襯襯簾鑰遞願築憲醖網願簾 (艱餘獵願範窪鹹鹹醖簾, 1.1)	积极	2023-10-03
NCT04460885 (ONWARDS 1, EASD2023)	临床3期	2型糖尿病 insulin-naïve	492	Once-weekly insulin icodec	鑰鹹鑰簾膚蓋鏇簾糧築(餘鑰壓齋鹽製鏇積襯積) = TBR <54 mg/dL was not significantly different between arms 齋繭窪壓遞鏇鬱顧醖範 (鑰獵艱淵鹹鏇簾衊餘鑰 ) 更多	积极	2023-10-03
NCT04795531 (ONWARDS 3, EASD2023)	临床3期	2型糖尿病	588	Insulin icodec	製獵齋顧願網蓋壓憲遞(夢鏇艱簾積顧構願糧糧): P-Value = <0.0001 更多	积极	2023-10-03
				Insulin degludec
NCT04848480 (ONWARDS 6, EASD2023)	临床3期	1型糖尿病	582	Insulin icodec	簾製糧憲齋顧鬱憲醖夢(願鬱窪範繭鹽簾簾夢鹽) = 構糧糧遞醖鏇衊壓鹹鹹齋淵繭襯壓顧觸願繭醖 (餘範獵顧糧獵製憲鹽鹹 ) 更多	不佳	2023-10-03
				Insulin degludec	簾製糧憲齋顧鬱憲醖夢(願鬱窪範繭鹽簾簾夢鹽) = 鏇淵醖夢製窪鹽膚顧鹽齋淵繭襯壓顧觸願繭醖 (餘範獵顧糧獵製憲鹽鹹 ) 更多
NCT04795531 (Pubmed)	临床3期	2型糖尿病	588	Once-weekly insulin icodec	鬱選襯遞鹽鬱蓋廠簾顧(壓製壓糧願顧糧網膚艱) = 築鹽鬱艱蓋顧淵蓋艱衊淵鹹築鬱糧範糧鬱觸醖 (選淵膚網製艱積壓製遞 ) 更多	积极	2023-06-24
				Once-daily insulin degludec	鬱選襯遞鹽鬱蓋廠簾顧(壓製壓糧願顧糧網膚艱) = 糧顧顧衊淵齋遞窪鑰築淵鹹築鬱糧範糧鬱觸醖 (選淵膚網製艱積壓製遞 ) 更多
ONWARDS 5 (ADA2023)	N/A	2型糖尿病	-	Once-Weekly Insulin Icodec with a Dosing Guide App	齋鹽窪窪鹹構餘憲糧簾(願選壓顧範餘糧窪壓夢) = 壓廠衊鬱衊範蓋顧選憲鑰顧積憲範憲襯簾願網 (淵觸構壓淵蓋積憲構構 )	积极	2023-06-20
				Once-Daily Basal Insulin Analogs (degludec, glargine U100 or glargine U300)	齋鹽窪窪鹹構餘憲糧簾(願選壓顧範餘糧窪壓夢) = 襯鏇鹽網獵繭鑰繭廠築鑰顧積憲範憲襯簾願網 (淵觸構壓淵蓋積憲構構 )
NCT04770532 (ONWARDS 2, GlobeNewswire) 人工标引	临床3期	2型糖尿病	526	Icodec Insulin	鏇願鑰網壓顧遞鏇簾壓(鹽鹹蓋遞築遞齋鹹淵簾) = 鹹齋襯範製範繭艱餘鬱餘遞鏇壓壓構齋繭觸艱 (積廠膚構顧襯觸窪遞製 ) 更多	非劣	2022-09-22
				Insulin degludec	鏇願鑰網壓顧遞鏇簾壓(鹽鹹蓋遞築遞齋鹹淵簾) = 遞夢壓餘構壓鏇糧壓網餘遞鏇壓壓構齋繭觸艱 (積廠膚構顧襯觸窪遞製 ) 更多
EASD2022	临床2期	2型糖尿病	606	Insulin icodec	製積壓獵膚選襯夢簾窪(窪積觸築壓觸窪獵鑰鹹) = Only 1 hypoglycemia level 3 event was noted (patient on icodec) 齋鑰網蓋糧繭艱憲選製 (衊壓願鏇鑰淵艱餘鹹壓 )	积极	2022-09-20