更新于：2024-04-26

Dapagliflozin

达格列净

更新于：2024-04-26

概要

概要

基本信息

药物类型

小分子化药

别名

(2S,3R,4R,5S,6R)-2-(4-Chloro-3-(4-ethoxybenzyl)phenyl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol、Dapagliflozin propandiol monohydrate、Dapagliflozin propanediol (USAN)

+ [22]

靶点

SGLT2

作用机制

SGLT2抑制剂(钠-葡萄糖协同转运蛋白-2抑制剂)

治疗领域

免疫系统疾病心血管疾病内分泌与代谢疾病+ [5]

在研适应症

1型糖尿病慢性心力衰竭慢性肾病+ [12]

非在研适应症

非胰岛素依赖型糖尿病2射血分数保留型心力衰竭射血分数降低的心力衰竭+ [12]

原研机构

Bristol Myers Squibb Co.

在研机构

Post Graduate Institute of Medical Education & ResearchAstraZeneca AB

AstraZeneca PLC

+ [5]

非在研机构

AstraZeneca Pharmaceuticals LP

最高研发阶段批准上市

首次获批日期

澳大利亚 (2012-10-22),

慢性肾病2型糖尿病心脏衰竭

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、快速通道 (美国)、优先审评 (中国)、优先审评 (澳大利亚)

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结构

分子式C24H35ClO9

InChIKeyGOADIQFWSVMMRJ-UPGAGZFNSA-N

CAS号960404-48-2

关联

763

项与达格列净相关的临床试验

NCT04818034 / Recruiting临床2期IIT

The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study

Cystinuria is an inherited autosomal recessive disorder of the kidney that is the result of an inability to reabsorb cystine from the urine. Supersaturation of cystine in the urine produces crystals that precipitate and form stones in the kidney, which can be a cause of obstruction, infection, and chronic kidney disease. Cystine stones constitute a major health challenge for affected individuals with cystinuria because of the frequent recurrence of painful symptoms and the current absence of effective, patient-accepting treatment.
A mainstay of therapy is breaking or preventing the cystine bond on the molecular level such that cystine (which is formed from the joining of two cysteine amino acids and their corresponding sulfur atoms) cannot precipitate in the urine. It is hypothesized that a glucose molecule may be able to do this if introduced into the urine. SGLT-2 inhibitors are a class of drug that are FDA approved to treat diabetes mellitus (DM) and heart failure by inhibiting an enzyme in the kidney that allows for reabsorption of glucose from the urine. This effectively increases the concentration of glucose in the urine. Our hypothesis suggests that administration of this drug to patients with cystine will introduce sufficient glucose into the urine to prevent the formation of cystine stones. To date, there has been no published data on the effectiveness of this therapy for this indication, although the dosage and administration would be identical to that already approved by the FDA for the treatment of DM and heart failure.

开始日期2025-05-02

申办/合作机构

The University of California, San Francisco

NCT06317051 / Not yet recruiting临床3期IIT

A Phase III/IV Factorial Randomized Double-blind Trial to Compare the Addition of Dapagliflozin vs Placebo and Rosuvastatin/Ezetimibe Versus Pitavastatin in Patients With HIV on Integrase Strand Transfer Inhibitor-based Antiretrovirals With Elevated Metabolic Risk

People with HIV are at a higher risk of cardiovascular diseases (CVD) due to the effects of the virus and its treatment. Integrase strand transfer inhibitors (INSTIs), a common HIV treatment, are associated with increased CVD risk and metabolic issues, such as weight gain and high blood pressure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, however, have been working well in reducing CVD events and hospitalizations due to heart failure, irrespective of diabetes presence. They also help in reducing weight and blood pressure. Pitavastatin has shown to work in lowering CVD events in people with HIV, but its availability is limited. This benefit is thought to be common to all statins, but this has not yet been confirmed. This study will examine the impact of dapagliflozin vs. placebo on metabolic parameters in people with HIV with high metabolic risk who are on INSTI-based ART.

开始日期2024-08-01

申办/合作机构

Kirby Institute

NCT06012266 / Not yet recruiting临床2期

Dose Rationale for Dapagliflozin and Empagliflozin in Paediatric Heart Failure: a Phase II.a Pharmacokinetics, Ease-of-swallow, Safety and Proof-of-concept Study Among Children 6-18 Years of Age

This study aims at exploring the use of Dapagliflozin and Empagliflozin in children and adolescents 6-18 years old with heart failure. These molecules are effective in reducing hospitalisations and mortality in adults with heart failure and are used in adolescents with type 2 diabetes mellitus, but little is known on children with heart failure. Particularly, the best dose to use in this population is currently unknown. This trial aims to:
1. define a dose rationale for this indication and age group (pharmacokinetic study),
2. assess and monitor safety,
3. assess ease-of-swallow,
4. explore middle-term (4-6 weeks) efficacy and efficacy markers.
Participants will be asked to attend 4 study visits over 4-6 weeks, and one end-study visit 2-12 weeks thereafter. Visits 1 and 3 will entail an 8h day-hospital stay, while Visits 2, 4 and the end-study visit will be outpatient clinics (approximately 2h). Participants will be asked to take the studied drug once daily during the 4-6 weeks of the study period.
All participants will take both Dapagliflozin and Empagliflozin: 6 will start with Dapagliflozin first (Visits 1-2) and then switch to Empagliflozin (Visits 3-4), while 6 will start with Empagliflozin first (Visits 1-2) and then switch to Dapagliflozin (Visits 3-4). No comparison group is foreseen for this study.

开始日期2024-08-01

申办/合作机构

Centre Hospitalier Universitaire Vaudois

[+2]

100 项与达格列净相关的临床结果

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100 项与达格列净相关的转化医学

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100 项与达格列净相关的专利（医药）

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2,622

项与达格列净相关的文献（医药）

2024-03-01·European Journal of Pharmacology

Investigation of co-treatment multi-targeting approaches in breast cancer cell lines

Article

作者: Battastini, Ana Maria Oliveira ; Scholl, Juliete Nathali ; Dias, Camila Kehl ; Longaray, Jéssica Brzoskowski ; Figueiró, Fabrício

In 2020, breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer in the world. Tumor microenvironment (TME) plays a critical role in resistance to standard therapies and tumor progression. Two key factors within the TME include adenosine, an immunosuppressive molecule, and glucose, which serves as the primary energy source for tumor cells. In this scenario, inhibiting the purinergic pathway and glucose uptake might be a promising strategy. Therefore, we sought to evaluated different treatment approaches in BC cells (Dapagliflozin, a SGLT2 inhibitor; Paclitaxel, the standard chemotherapy for BC; and ARL67156/APCP, inhibitors of CD39 and CD73, respectively). The expression of some membrane markers relevant to resistance was assessed. BC cell-lines (MCF-7 and MDA-MB-231) were co-treated and cell viability, cell cycle, and annexin/PI assays were performed. Our analysis showed promising results, where the combination of these compounds led to cell death by apoptosis/necrosis and cell cycle arrest. Dapagliflozin showed more impact on early apoptosis, whereas Paclitaxel led to late apoptosis/necrosis as the main mechanism of cell death. Inhibiting purinergic signaling also contributed to reducing cell viability together with the other drugs, suggesting it could have an influence on breast cancer survival mechanisms. Indeed, the overexpression of the NT5E gene in patients with ER+ tumors is strongly associated with reduced overall survival and progression-free interval. However, more studies are needed to fully understand the interactions and mechanism underlying these co-treatment multi-targeting approaches.

2024-03-01·Journal of Pharmaceutical and Biomedical Analysis

Bariatric surgery and changes in metformin distribution: About a fatal case

Article

作者: Feisthauer, E ; Kintz, P ; Blanchot, A ; Gheddar, L ; Raul, J S ; Arbouche, N ; Ameline, A

A 65 year-old woman, suffering from mellitus type 2 diabetes and obesity, died at home, three days after bariatric surgery (Roux-en-Y gastric by-pass: RYGB). Her treatment, including metformin and dapagliflozin, was stopped before surgery and not postoperatively reinstalled. A forensic autopsy, toxicological and histological analyses were performed. No macroscopic or microscopic evidence of digestive perforation or peritonitis was identified, excluding an early surgery complication as the cause of death. Toxicological analysis revealed the presence of Metformin in all matrices tested, with a potentially fatal blood concentration. Death was attributed to lactic acidosis caused by a metformin overdose. With no evidence for suicide by ingestion of metformin, the authors supposed that the bariatric surgery might have caused changes in the absorption of metformin, leading to a rapid overdose and death. The only study in the literature on this subject, demonstrated a significant increase in the bioavailability of metformin following oral administration in gastric bypass patients. Thus, it can be anticipated that a therapeutic dose can become toxic when administrated to a subject who recently modified her digestive equipment. As this represents the first case of metformin overdose following bariatric surgery, further cases will be needed to confirm our initial observations.

2024-02-28·Nephrology Dialysis Transplantation

Efficacy and safety of zibotentan and dapagliflozin in patients with chronic kidney disease: study design and baseline characteristics of the ZENITH-CKD trial

Article

作者: Mercier, Anne-Kristina ; Wijkmark, Emma ; Althage, Magnus ; Heerspink, Hiddo J L ; Ambery, Philip ; Dwyer, Jamie P ; Sunnåker, Mikael ; Law, Gordon ; Turton, Michelle ; Ahlström, Christine ; Greasley, Peter J ; Wheeler, David C ; Lin, Min

ABSTRACT:

Background:

Sodium–glucose co-transporter 2 inhibitors (SGLT2is) are part of the standard of care for patients with chronic kidney disease (CKD), both with and without type 2 diabetes. Endothelin A (ETA) receptor antagonists have also been shown to slow progression of CKD. Differing mechanisms of action of SGLT2 and ETA receptor antagonists may enhance efficacy. We outline a study to evaluate the effect of combination zibotentan/dapagliflozin versus dapagliflozin alone on albuminuria and estimated glomerular filtration rate (eGFR).

Methods:

We are conducting a double-blind, active-controlled, Phase 2b study to evaluate the efficacy and safety of ETA receptor antagonist zibotentan and SGLT2i dapagliflozin in a planned 415 adults with CKD (Zibotentan and Dapagliflozin for the Treatment of CKD; ZENITH-CKD). Participants are being randomized (1:2:2) to zibotentan 0.25 mg/dapagliflozin 10 mg once daily (QD), zibotentan 1.5 mg/dapagliflozin 10 mg QD and dapagliflozin 10 mg QD alone, for 12 weeks followed by a 2-week off-treatment wash-out period. The primary endpoint is the change in log-transformed urinary albumin-to-creatinine ratio (UACR) from baseline to Week 12. Other outcomes include change in blood pressure from baseline to Week 12 and change in eGFR the study. The incidence of adverse events will be monitored. Study protocol–defined events of special interest include changes in fluid-related measures (weight gain or B-type natriuretic peptide).

Results:

A total of 447 patients were randomized and received treatment in placebo/dapagliflozin (n = 177), zibotentan 0.25 mg/dapagliflozin (n = 91) and zibotentan 1.5 mg/dapagliflozin (n = 179). The mean age was 62.8 years, 30.9% were female and 68.2% were white. At baseline, the mean eGFR of the enrolled population was 46.7 mL/min/1.73 m2 and the geometric mean UACR was 538.3 mg/g.

Conclusion:

This study evaluates the UACR-lowering efficacy and safety of zibotentan with dapagliflozin as a potential new treatment for CKD. The study will provide information about an effective and safe zibotentan dose to be further investigated in a Phase 3 clinical outcome trial.

Clinical Trial Registration Number:

NCT04724837

557

项与达格列净相关的新闻（医药）

2024-04-25

·药渡

全球药企收入排行TOP20出炉，谁是你心中的No.1？（上）

来源：药渡撰文：四月的雨编辑：哦呼近日，fiercepharma公布了2023年度全球药企收入排行TOP20，强生重回榜首，2023年度销售额达852亿美元，同比增长6.5%，而辉瑞由于新冠疫苗Comirnaty和新冠抗病毒药物Paxlovid的销量下降，销售额由2022年的1003亿美元降至585亿美元，下降41%。除上述两家制药公司外，大家熟知的罗氏、默沙东、诺华、GSK以及阿斯利康等公司纷纷入榜，下表1为2023年度全球药企收入排行TOP1-TOP10。表1.2023年度全球药企收入排行TOP1-TOP10TOP1强生2023年收入：851.6亿美元，相比于2022年的799.9亿美元，同比增长6.5%。药物方面，强生最畅销的药物依旧是免疫学药物Stelara，2023年销售额达108.6亿美元，2022年销售额为97.2亿美元。而让强生较为头疼的是，Stelara的专利期仅剩一年，该药物即将面对生物类似药的冲击。除了Stelara之外，强生的银屑病药物Tremfya销售额为31.5亿美元，同比增长18%。为了应对Stelara专利到期，强生预计到2030年将新增20多种上市药物以及50种适应症扩展。TOP2罗氏2023年收入：653.2亿美元，相比于2022年的662.6亿美元，同比下降7.2%。产品方面，2023年新冠相关的收入减少43亿法郎，约48亿美元，但眼病药物Vabysmo成为了罗氏的一匹黑马，在上市第二年Vabysmo的销售额已达到27亿美元，罗氏2023年最畅销产品依旧是多发性硬化症药物Ocrevus，销售额达71.3亿美元。罗氏目前正进行着包含82种新分子实体在内的共146个临床项目，其中肿瘤学是其研发工作的核心领域。TOP3默沙东2023年收入：601亿美元，相比于2022年的593亿美元，同比增长1.4%。谈到默沙东，自然就避不开其核心产品“药王”Keytruda，该药物预计将于2028年专利到期，去年该药物的收入达250亿美元，占默沙东公司总收入的41%。Edward Jones医疗保健分析师John Boylan预计该药物2025年销售额将达到300亿美元。但不可避免的是，一款药物的专利期时长终究是有限的，Keytruda将于2028年在美国和中国失去专利保护，所以默沙东需要找到一种可以替代甚至超越Keytruda的药物来规避专利到期对销售额所带来的的影响。因此默沙东频频出手扩大产品管线，2021年收购Acceleron以及2023年收购Prometheus位列当年生物制药行业并购交易前三名。除了直接收购生物技术外，默沙东公司在10月份还引起了轰动，它预先花费了40亿美元，并承诺支付180亿美元的持续付款和里程碑付款，以获得第一三共公司三种抗体药物偶联物的权利。默沙东在ADC领域动作频频，颇有大展拳脚的架势。全力推进ADC管线的研发，足以见得默沙东对于ADC药物的重视。TOP4辉瑞2023年收入：585亿美元，相比于2022年的1003亿美元，同比下降41%。受新冠疫情影响，辉瑞在2022年大展神威，全年销售额达1003亿美元。而当新冠褪去，辉瑞逐渐回归现实。尽管辉瑞2023年销售额下降41%，但若是去掉新冠药物及疫苗收入后，辉瑞2023年销售额还增长了7%。药物方面，辉瑞的几种关键药物和疫苗正在崛起。RSV疫苗Abrysvo在5月份获得初步批准后，去年创造了8.9亿美元的收入。除了Abrysvo之外，辉瑞的Nurtec ODT在2023年的收入为9.28亿美元，销售额同比增长335%。此外，辉瑞的心脏病药物Vyndaqel和Vyndamax继续保持强劲的势头，2023年销售额达33亿美元，同比增长36%。交易方面，辉瑞也是出手阔绰。2023年5月，辉瑞斥资430亿美元收购ADC药企Seagen，以扩大其肿瘤业务，该交易于2023年12月完成。Seagen目前已批准了25种癌症药物，涵盖40多种适应症，其中九种药物是重磅药物或有潜力成为重磅药物（年销售额达10亿美元）。TOP5艾伯维2023年收入：543亿美元，相比于2022年的581亿美元，同比下降6%。艾伯维在2013年开始崭露头角，仅用10年时间便位列全球制药企业前5名，完成这一大壮举很大程度上要归功于修美乐（Humira）。但修美乐从2023年初开始就面临美国生物类似药的竞争。随着多家企业推出生物类似药，修美乐市场份额被不断瓜分，2023全年销售额同比下降32%。修美乐专利到期，寻找到新的继任者则至关重要。免疫学药物Skyrizi（瑞莎珠单抗）和Rinvoq作为双子星，可以一定程度上弥补修美乐专利到期所造成的影响。2023年，Skyrizi的销售额为77亿美元，同比增长50%，Rinvoq销售额为39亿美元，同比增长57%。两者销售额共计超过100亿美元，到2027年将超过修美乐达到270亿美元的峰值收入。尽管如此，目前这对组合的强劲表现仍不足以抵消修美乐销售额下滑带来的影响。为应对修美乐专利到期，艾伯维屡屡完成重大交易。2019年，艾伯维以630亿美元收购Allergan，2023年以101亿美元收购了ADC药物公司ImmunoGen，一周后，艾伯维又以87亿美元收购Cerevel Therapeutics的交易，以加强神经领域产品管线。TOP6赛诺菲2023年收入：466亿美元，相比于2022年的452亿美元，同比增长0.2%。与默沙东的处境相类似，赛诺菲也对一款药物严重依赖，这款药物就是这Dupixent（度普利尤单抗）。Dupixent由再生元和赛诺菲联合开发，2023年销售额为115.88亿美元，同比增长33%，自2017年首次获得FDA批准用于治疗特应性皮炎以来，其商业势头持续强劲，该药物约占赛诺菲收入的25%。除此之外，赛诺菲的多发性硬化症药物Aubagio在2023年收到仿制的冲击，销售额暴跌53%至9.55亿欧元。疫苗组中，赛诺菲和阿斯利康针对婴儿的新型RSV抗体Beyfortus去年为赛诺菲分得5.47亿欧元，随着使用量的持续增加，今年的Beyfortus销售额将超10亿美元。TOP7阿斯利康2023年收入：458.1亿美元，相比于2022年的443.5亿美元，同比增长3.3%。早在2014年，阿斯利康就制定了2023年实现450亿美元收入的目标，如今也是按照预期实现了这一目标。产品方面，肿瘤领域药物再次实现最大增长，销售额达到171亿美元，增长20%，其中还不包括第一三共的抗体药物偶联物Enhertu带来的约10亿美元的收入。除了Enhertu之外，AZ（AstraZeneca，阿斯利康）的免疫肿瘤药物组合Imfinzi和Imjudo合计销售额达42亿美元，同比增长55%。在AZ的肿瘤产品中，最火热的药物仍属于Tagrisso，该药物销售额为58亿美元，同比增长9%。而AZ的头把交椅给到了SGLT2抑制剂Farxiga，2023年Farxiga销售额达近60亿美元。交易方面，为了进一步加强其在代谢疾病领域的地位，AZ于2023年11月同意向中国的Eccogene公司支付1.85亿美元购买口服GLP-1激动剂，AZ认为该药物具有很大的潜力。TOP8诺华2023年收入：454.4亿美元，相比于2022年的422.1亿美元，同比增长7.7%。诺华公司去年剥离其仿制药和生物类似药业务山德士后，成为一家纯粹的创新药物公司。由于分拆，诺华的报告销售额下降，其在全球最大制药公司中的排名也下降。2023年，诺华收入达454亿美元，而山德士的净销售额为96亿美元。产品方面，其心脏病药物Entresto和多发性硬化症注射剂Kesimpta贡献了最多的销售额，分别为60亿美元和20亿美元。除此以外，Pluvicto以及CDK4/抑制剂Kisqali也引起了大家的关注。诺华于 2022年底首次报告称，Pluvicto治疗早期前列腺癌的PSMAfore试验已达到目标。Kisqali更是预计在转移性疾病领域的销售额能够达到40亿美元，在辅助治疗领域的销售额超过30亿美元。此外，诺华的siRNA药物PCSK9抑制剂Leqvio获批上市，2023年销售额约为4亿美元。在并购方面，诺华去年以32亿美元收购了Chinook Therapeutics。随后的3期临床结果显示，该交易的核心产品Atrasentan已达到治疗IgA肾病的主要终点。诺华还预付了5亿美元购买了专注于siRNA的DTx Pharma，其中包括针对遗传性神经肌肉疾病的临床前治疗，目前尚无批准的药物可用于治疗这种疾病。RNA、放射性配体、细胞和基因治疗是诺华除传统小分子和生物制剂之外重点发展的三个技术平台。TOP9百时美施贵宝2023年收入：450亿美元，相比于2022年的462亿美元，同比下降2%。受专利悬崖和未来与通货膨胀削减法案 (IRA) 相关的影响，当前的百时美施贵宝正处于过渡期。与辉瑞合作的血液稀释剂Eliquis被列为首批医保谈判的10种药物之一，在这种影响下，百时美施贵宝坚守住了阵地。2023年Eliquis的全球销售额为122 亿美元，同比增长4%。仅在美国，销售额就增长了10%，达到86亿美元。但由于将于2026年生效的新IRA定价，这一增长速度可能很快就会放缓。除了Eliquis之外，来那度胺仍然是卖的最火热药物之一，2023年销售额为60亿美元。此外，BMS的PD-1抑制剂Opdivo在2023年贡献了90亿美元的销售额，加上小野制药报告的该药物的1481亿日元（10 亿美元）销售额，该药物突破了100亿美元销售额大关。TOP10葛兰素史克2023年收入：384亿美元，相比于2022年的361亿美元，同比增长3.4%。疫苗是葛兰素史克增长的动力之一，带状疱疹疫苗Shingrix在2023年销售额达34亿英镑，RSV疫苗Arexvy获FDA批准，这是世界上首款针对60岁及以上成年人的RSV疫苗。Arexvy在上市当年就创造了12亿英镑的收入，GSK预计Arexvy的峰值销售额将达到30亿英镑。除了Arexvy之外，葛兰素史克的口服贫血药物Jesduvroq去年获得FDA批准，成为首个进入美国市场治疗慢性肾病的HIF-PH抑制剂。交易及并购方面，葛兰素史克去年斥资20亿美元收购了Bellus Health，并获得了临床3期P2X3拮抗剂camlipixant。小结以上就是2023年度全球药企收入排行TOP20中的前十名，由于文章篇幅有限，第11-20名将在下篇文章中介绍，谁会成为你心中的Number one？参考文献[1]https://www.fiercepharma.com/pharma/top-20-pharma-companies-2023-revenue*声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！点击下方“药渡“，关注更多精彩内容FDA正式发声，黑框警告下的CAR-T疗法2024年值得关注的5个细胞和基因治疗决策TPD技术最新发展：溶酶体或蛋白酶体直接参与的靶向蛋白质降解点击蓝字关注我们

专利到期并购抗体药物偶联物生物类似药疫苗

2024-04-25

·FiercePharma

AstraZeneca CEO says platform deals largely done after M&As in vaccines, radioligand, cell therapy

AstraZeneca delivered a strong start to 2024 as both oncology and biopharmaceutical divisions surpassed $5 billion quarterly sales for the first time. After AstraZeneca’s recent acquisitions of various technologies across different therapeutic areas, some investors started to wonder if the British pharma is stretching too thin. To hear CEO Pascal Soriot explain it, the deals were made to build the company’s future. “This portfolio actually gives us the opportunity to combine,” Soriot said on the company’s first-quarter earnings call. In oncology, AZ last month unveiled a $2 billion deal to acquire targeted radiotherapy specialist Fusion Pharmaceuticals. It followed a $1 billion buyout unveiled in December for the cell therapy biotech Gracell Biotechnologies. These add to AZ’s existing checkpoint inhibitor offerings and antibody-drug conjugate capabilities as well as an emerging portfolio of bispecific antibodies. In the cardiovascular and metabolic disease field, AZ in November said it would pay $185 million upfront to in-license an oral GLP-1 agonist from Eccogene. AZ has said the drug may hold potential for combinations including with its SGLT2 agent Farxiga. As for vaccines, AZ in December entered into an agreement to acquire Icosavax, which has a protein virus-like particle platform and a phase 3-ready RSV vaccine candidate. “I think there’s sometimes a misperception of what we’re trying to do,” Pascal said. “We’re not trying to build a vaccine business like vaccine companies have. We are actually targeting vaccines that will be […] synergistic to oncology or respiratory disease products.” With that synergy strategy, Soriot argued that the company is not stretching too thin. “The challenge and the opportunity in our industry is always to be able to think about today, but also the long term,” the chief executive said. But M&A activities—at least in terms of technology platform deals—will slow down at AZ, Soriot added. “I think we have acquired and built most of what we need for now and we need to execute on what we’ve got,” Soriot said. “But it doesn’t mean of course BD will come down to zero.” Soriot’s comment comes as AstraZeneca delivered a strong start to 2024 as both oncology and biopharmaceutical divisions surpassed $5 billion quarterly sales for the first time and rare disease crossed the $2 billion mark. In a Thursday note to clients, ODDO BHF analysts called the results “much stronger than expected.” AZ’s total revenue, which includes both product sales and alliance revenue, beat analysts’ estimates by 7%, reaching $12.7 billion in the first quarter. The stellar performance was surprisingly driven in a large part by the 10-year-old Farxiga. As it nears a mandated price cut under the Inflation Reduction Act, the SGLT2 inhibitor brought in $1.89 billion sales. The number marked a 45% growth year over year and handily beat Wall Street’s consensus projection by 19%, according to ODDO BHF. The launch of an authorized generic in the U.S. helped fuel Farxiga’s jump because it offers a low-cost option for patients, the company’s biopharmaceuticals chief Ruud Dobber told investors during a call Thursday. Dobber declined to offer a sales breakdown between the two versions of Farxiga. While Farxiga saw “solid growth” in emerging markets despite generic competition in some countries, Dobber warned that the drug is expected to be included in China’s volume-based procurement program later this year. The Chinese initiative, which targets off-patent drugs, will mean price cut and likely market share loss. Still, investors have most of their attention on some newer drugs, including in the oncology department. HER2-targeted Enhertu generated $879 million sales in the first quarter between AZ and its partner Daiichi Sankyo. The antibody-drug conjugate enjoyed “sequential market share growth” in HER2-positive metastatic breast cancer and “continued adoption” in HER2-low disease, AZ’s oncology business head Dave Fredrickson said on the call. AZ and Daiichi expect to report data from the DESTINY-Breast06 trial by June, which could move Enhertu one line earlier into second-line HER2-low breast cancer and potentially in patients with even lower expression of HER2 than the current HER2-low definition. The trial has already reached primary completion about a month ago, which means the data necessary for the primary endpoint analysis were all in. In oncology, Tagrisso remained the biggest drug with nearly $1.6 billion in sales in the first quarter, good for 15% growth year over year at unchanged exchange rates. The EGFR inhibitor looks on track to reach patients with unresectable stage 3, EGFR-mutant non-small cell lung cancer after a recent phase 3 trial win.

并购疫苗临床3期免疫疗法

2024-04-25

·赛柏蓝

国采轮番纳入，糖尿病用药Top20洗牌（附名单）

编者按：本文来自米内网，作者未晞；赛柏蓝授权转载，编辑相宜4月23日，胰岛素专项协议期满接续采购如期开标，49个产品拟中选，备受业界关注的第十批国采如箭在弦，新一轮市场洗牌即将来临。01国采席卷10个小类市场逐渐恢复活力经历了第二批、第三批、第四批、第五批、第六批（胰岛素专项）、第七批以及第九批国采，已有38个糖尿病用药（按产品名统计，涉及27个品种）中标，覆盖a-葡萄糖甙酶抑制剂、SGLT2抑制剂、DPP-4抑制剂、磺胺类及尿素衍生物、口服复方降糖药、双胍类、胰岛素及其类似药等10个小类，目前仅GLP-1受体激动剂未有产品纳入国采。图1：国采前后糖尿病用药的销售情况（单位：万元）在重点省市公立医院终端，2013-2019年（国采前）糖尿病用药的销售规模呈持续增长态势，2019年首次突破70亿元。2020年第二批国采启动后该类药物的销售额出现负增长，2021年后逐步恢复活力。数据显示，2023年该类药物的销售规模涨至74亿元以上，近四年的国采压力已基本抵消。表1：国采前后糖尿病用药TOP5小类的变化情况国采“以价换量”快速改变了畅销小类的排名，GLP-1受体激动剂、SGLT2抑制剂、口服复方降糖药3个小类快速成长，已成为了2023年的TOP1、TOP3、TOP5小类。而昔日的冠军胰岛素及其类似药在2023年失去了榜首位置，排名下降1位，市场份额跌至22.60%，为历史最低位。可见，糖尿病用药市场整体活力已恢复，但品类格局已发生了翻天覆地的变化。02新10亿品种大涨118%8个亿级品种表现相反在重点省市公立医院终端糖尿病用药市场，2019年过亿品种有17个，其中阿卡波糖的销售额超过了12亿元；2020年过亿品种有18个，2021-2022年的TOP20品种销售额均超过1亿元，这三年均没有超10亿品种；到了2023年，过亿品种有19个，司美格鲁肽成为了新的超10亿品种。表2：2019年及2023年糖尿病用药TOP20品种变化情况注：销售额低于1亿元用*表示图2：司美格鲁肽的销售情况（单位：万元）诺和诺德的司美格鲁肽注射液在2021年进入中国市场，随后进入国家医保谈判目录，2022年在重点省市公立医院终端成为了糖尿病用药TOP4品种，2023年该品种的销售额首次突破10亿元，增长率高达118.63%，一跃成为新的TOP1品种。2024年1月，诺和诺德的司美格鲁肽片获批进口，成为了国内首款上市的口服GLP-1受体激动剂，随着新产品加入战局，该品种的销售额有望继续攀升。对比2019年及2023年的糖尿病用药TOP20品种，有11个品种顶住了压力继续留在榜单上，除了司美格鲁肽成功封王，度拉糖肽、德谷门冬双胰岛素、西格列汀二甲双胍、吡格列酮二甲双胍、德谷胰岛素、恩格列净、聚乙二醇洛塞那肽、沙格列汀二甲双胍8个品种近几年也是成绩亮眼，挺进了2023年TOP20品种榜单。图3：3个口服复方降糖药的销售情况（单位：万元）近几年口服复方降糖药呈现快速增长态势，2019年在重点省市公立医院终端糖尿病用药市场的份额仅有1.7%，2023年涨至7.5%以上，潜力不容小觑。西格列汀二甲双胍和吡格列酮二甲双胍在2021年已成为亿元级别品种，2023年分别涨至2亿元、1.8亿元以上，而沙格列汀二甲双胍在2023年也到了9000万元水平，下一个亿级口服复方降糖药或将在2024年诞生。值得注意的是，有9个在2019年上榜的畅销品种消失在了2023年的TOP20品种榜单中，涉及8个亿元级别品种，包括了精蛋白生物合成人胰岛素(精蛋白重组人胰岛素)(精蛋白人胰岛素)、格列美脲、赖脯胰岛素、瑞格列奈、地特胰岛素、格列齐特、沙格列汀、维格列汀。图4：3个畅销胰岛素及其类似药的销售情况（单位：万元）2019年精蛋白生物合成人胰岛素(精蛋白重组人胰岛素)(精蛋白人胰岛素)、赖脯胰岛素、地特胰岛素在重点省市公立医院终端的销售额分别达到了3亿元、2.5亿元、2.1亿元以上，随后在2021年纳入了第六批国采（胰岛素专项），到了2023年精蛋白生物合成人胰岛素(精蛋白重组人胰岛素)(精蛋白人胰岛素)的销售额7500万元、赖脯胰岛素的销售额6200万元、地特胰岛素的销售额5900万元水平。2019年格列美脲、瑞格列奈、格列齐特在重点省市公立医院终端的销售额均在2亿元以上，格列美脲在2020年纳入第二批国采，瑞格列奈和格列齐特在2021年纳入第四批国采，到了2023年格列美脲仅剩2300万元、瑞格列奈4500万元、格列齐特8300万元水平。沙格列汀和维格列汀均为DPP-4抑制剂，2019年在重点省市公立医院终端的销售额均超过1亿元，维格列汀在2020年纳入第三批国采，沙格列汀在2021年纳入第五批国采，2023年，沙格列汀6500万元、维格列汀1600万元。03国产品牌逆境奋斗扬子江、中美华东、豪森“称霸一方”在重点省市公立医院终端糖尿病用药市场，2019年TOP20品牌中国产品牌占5个，2020年国产品牌占4个，2021-2022年国产品牌均占3个，2023年国产品牌回升至4个，进口品牌霸屏的态势依然存在，国内药企在逆势中不断成长，也能“称霸一方”。表3：2023年糖尿病用药TOP20品牌中国产品牌的销售情况注：销售额低于1亿元用*表示扬子江南京海陵药业的依帕司他片是治疗糖尿病神经病变的药物，2019年在重点省市公立医院终端的销售额接近1.2亿元，是其他糖尿病用药TOP2品牌，2020年起成为该小类的TOP1品牌，随后一直保持领军优势，在2023年销售额突破2亿元。杭州中美华东制药的吡格列酮二甲双胍片(15mg/500mg)2019年在重点省市公立医院终端的销售额在5900万元水平，2021年突破1.2亿元，2023年涨至1.6亿元，成为了口服复方降糖药TOP2品牌，也是目前最畅销的口服复方降糖药国产品牌。聚乙二醇洛塞那肽注射液是豪森药业集团在2019年获批的1类新药，当年在重点省市公立医院终端的销售额不到100万元。2020年该品牌成功超越了上海仁会生物制药的贝那鲁肽注射液，成为了最畅销的GLP-1受体激动剂国产品牌。近几年，豪森药业集团的聚乙二醇洛塞那肽注射液一直保持高速增长态势，2023年的销售额首次突破1亿元。04胰岛素接续采购4个超10亿产品备战第十批国采3月29日，上海阳光医药采购网发布了《全国药品集中采购文件（GY-YD2024-1）》，宣布开展胰岛素专项协议期满接续采购工作，据悉，本次接续采购覆盖品种范围与首轮相同，包括6个采购组、11个报价单元，在4月23日开标。表4：全国药品集中采购（胰岛素专项接续）拟中选结果来源：上海阳光医药采购网据国家医保局官微消息，本次胰岛素专项接续采购共13家企业的53个产品参与竞标，49个产品拟中选，中选率达92%。中选价格是稳中有降，在首轮集采降价基础上又降低了3.8%，报价较低的A类中选产品比例从上一轮的40%提高到71%。从拟中选结果看，宜昌东阳光长江药业的精蛋白人胰岛素混合注射液(30R)、门冬胰岛素注射液、门冬胰岛素30注射液，江苏万邦生化医药集团的赖脯胰岛素注射液、甘精胰岛素注射液，山东新时代药业的甘精胰岛素注射液等11个产品为新中标，进一步刺激市场“腾笼换鸟”。备受业界关注的第十批国采也是箭在弦上，一触即发。目前糖尿病化药已过评/视同过评的产品数量超过50个，而暂未纳入国采且竞争企业≥5家（原研+过评）的产品有7个。表5：竞争企业≥5家的糖尿病化药注：销售额低于1亿元用*表示在中国城市公立医院、县级公立医院、城市社区中心及乡镇卫生院（简称中国公立医疗机构）终端，磷酸西格列汀片、达格列净片、依帕司他片和利格列汀片2022年的销售额均超过10亿元。磷酸西格列汀片目前由默沙东领军市场，正大天晴药业集团、广东东阳光药业、石药欧意药业等20多家国内药企按新分类获批视同过评。达格列净片目前由阿斯利康领军市场，江苏豪森药业集团、成都倍特药业、南京正大天晴制药等9家国内药企按新分类获批视同过评。利格列汀片目前由勃林格殷格翰领军市场，四川科伦药业、浙江华海药业、齐鲁制药等8家国内药企按新分类获批视同过评。这些重磅产品被国内巨头紧紧盯着，“国产替代原研”大有可为，同时借助国采加速国产品牌渗透，TOP20品牌榜单的“国产占比”有望逐步提升。资料来源：米内网数据库、上海阳光医药采购网等END内容沟通：13810174402医药代表交流群扫描下方二维码加入银发经济市场机遇交流群扫描下方二维码加入左下角「关注账号」，右下角「在看」，防止失联

生物类似药带量采购上市批准

100 项与达格列净相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09763	达格列净	A10BK01	DB06292

研发状态

适应症	最高研发状态	国家/地区	公司
2型糖尿病	批准上市	冰岛更多	AstraZeneca AB 更多
慢性肾病	批准上市	挪威更多	AstraZeneca AB 更多
心肌梗塞	无进展	韩国更多	AstraZeneca PLC 更多
肾病	无进展	美国更多	AstraZeneca Pharmaceuticals LP 更多
休克	无进展	斯洛伐克更多	AstraZeneca PLC 更多

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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


NCT04298229 (DICTATE-AHF, Pubmed)	临床3期	2型糖尿病 \| 心脏衰竭	240	Dapagliflozin 10 mg once daily	壓淵鏇構餘廠獵淵繭廠(願構襯淵鏇鬱鑰鏇遞膚): OR = 0.65 (95% CI, 0.41 ~ 1.02), P-Value = 0.06	积极	2024-04-09
				Dapagliflozin
NCT03782259 (Pubmed)	临床4期	2型糖尿病 IL-1B \| TNFα \| IL-6 ... 更多	62	Dapagliflozin 10 mg	糧願廠廠齋窪鬱淵遞製(醖願願積餘壓蓋襯鏇壓) = 簾夢鹹選遞餘鬱鹽獵鏇齋積顧膚選蓋製獵糧願 (構簾壓壓觸簾選膚鏇糧 )	-	2024-03-25
NCT04298229 (CTgov)	临床3期	心脏衰竭 \| 2型糖尿病	240	diuretic (Structured Usual Care)	網膚選夢鏇醖膚壓遞鬱(糧餘廠積齋鬱鹽選餘衊) = 醖齋顧範窪範網艱鬱夢齋蓋鹹製觸齋淵顧製鏇 (選築製壓獵鏇憲蓋構範, 選鹽膚鑰顧糧鑰範顧襯 ~ 夢蓋簾鏇願觸願鹹製蓋) 更多	-	2024-03-15
				Dapagliflozin (Dapagliflozin Plus Structured Usual Care)	網膚選夢鏇醖膚壓遞鬱(糧餘廠積齋鬱鹽選餘衊) = 醖網鬱簾憲製憲齋獵窪齋蓋鹹製觸齋淵顧製鏇 (選築製壓獵鏇憲蓋構範, 夢衊構膚壓築製範顧遞 ~ 壓鏇糧窪觸鹹繭選醖範)
NCT02777073 (CTgov)	N/A	高血糖 \| 1型糖尿病	43	Victoza (Liraglutide 1.8 mg)	網願糧構範繭衊廠廠遞(願網淵願夢觸襯積襯鬱) = 夢餘範遞餘醖餘鬱構獵窪餘蓋顧蓋襯鑰鹹糧鬱 (艱廠鏇壓選夢廠餘齋獵, 夢衊憲壓範襯範鹹簾鹽 ~ 艱製繭鹽觸壓淵製淵鏇) 更多	-	2024-02-29
				Placebo (Placebo)	網願糧構範繭衊廠廠遞(願網淵願夢觸襯積襯鬱) = 繭觸獵壓範積壓觸淵鹽窪餘蓋顧蓋襯鑰鹹糧鬱 (艱廠鏇壓選夢廠餘齋獵, 蓋獵顧糧鬱範窪窪獵憲 ~ 獵憲糧膚鏇齋蓋觸夢鹽) 更多
NCT02962492 (CTgov)	N/A	1型糖尿病	70	Placebo (Placebo Arm:)	獵艱積艱窪膚願醖憲簾(鹽廠願襯鹹餘獵選壓積) = 範糧蓋醖積範鏇淵醖築網鬱窪網窪遞遞選鹽餘 (夢構醖顧構鑰觸遞構淵, 鹽繭顧構夢願鹽願網鹹 ~ 齋蓋鹹築鬱繭窪構積選) 更多	-	2024-02-29
				Dapagliflozin (Dapagliflozin Arm:)	獵艱積艱窪膚願醖憲簾(鹽廠願襯鹹餘獵選壓積) = 顧構糧淵積鏇壓餘顧醖網鬱窪網窪遞遞選鹽餘 (夢構醖顧構鑰觸遞構淵, 獵範願網壓餘襯顧鬱糧 ~ 鑰醖網淵憲齋艱鬱願鬱) 更多
NCT03619213 (DELIVER, Pubmed)	临床3期	射血分数降低的心力衰竭 natriuretic peptides	1,151	Dapagliflozin	壓膚鏇範鏇繭遞繭衊構(餘築醖窪壓遞蓋窪築壓): hazard ratio = 0.38 (95% CI, 0.18 ~ 0.79)	积极	2024-01-24
				Placebo
NCT02518945 (CTgov)	临床3期	1型糖尿病	26	Insulin+Liraglutide (Placebo)	壓觸廠餘壓鬱鏇糧壓鑰(襯顧顧鹹鑰觸糧網窪餘) = 簾選製鑰構鏇選繭繭選觸鹽艱窪選鏇膚壓膚蓋 (襯醖觸鑰鬱餘艱選觸齋, 齋膚鬱憲鹽鹹艱淵簾製 ~ 簾繭選築鑰鑰醖願遞選) 更多	-	2024-01-24
				Insulin+Liraglutide+Dapagliflozin (Active Drugs)	壓觸廠餘壓鬱鏇糧壓鑰(襯顧顧鹹鑰觸糧網窪餘) = 壓夢夢淵鏇構鬱鬱襯壓觸鹽艱窪選鏇膚壓膚蓋 (襯醖觸鑰鬱餘艱選觸齋, 鑰構鏇築餘憲積觸蓋蓋 ~ 構積廠顧蓋顧鏇觸艱簾) 更多
NCT04401904 (CTgov)	临床1/2期	糖尿病前期 \| 肥胖	20	Dapagliflozin 10 mg (Dapagliflozin)	廠齋衊鬱糧遞觸網醖蓋(網積願餘獵積襯壓淵齋) = 鏇夢艱糧遞鏇艱窪衊製積願鏇鹽憲遞廠簾鏇膚 (鬱壓襯糧顧夢艱願壓憲, 廠顧鏇壓壓膚願鏇選壓 ~ 網製網築繭獵鏇夢構選) 更多	-	2024-01-05
				Nutritional counseling (Nutritional Counseling)	廠齋衊鬱糧遞觸網醖蓋(網積願餘獵積襯壓淵齋) = 鹹鏇鑰夢顧構醖選夢觸積願鏇鹽憲遞廠簾鏇膚 (鬱壓襯糧顧夢艱願壓憲, 襯鏇鑰簾憲窪窪鬱鏇醖 ~ 網廠齋夢餘膚艱餘築蓋) 更多
NCT03782259 (CTgov)	临床4期	心肌纤维化 \| 肌强直性营养不良 \| 2型糖尿病 ... 更多	62	Placebo (Placebo)	醖艱壓網築艱壓鹹蓋膚(觸淵鹹鏇築遞齋夢製鏇) = 蓋襯簾鹹餘築構觸範齋襯簾顧積繭衊鑰蓋鏇鏇 (憲糧選積壓顧範網積廠, 膚糧膚鏇憲廠網憲製鑰 ~ 憲顧廠糧壓獵醖觸淵窪) 更多	-	2023-12-29
				dapagliflozin (Active)	蓋憲夢壓糧淵構衊網衊(範糧壓構築艱獵選鏇鏇) = 齋憲鹽繭遞範獵願願鏇壓壓獵製遞選鏇鏇選壓 (餘糧淵遞鏇壓齋衊築鬱, 憲願築壓遞齋鑰選構鏇 ~ 積衊醖衊窪蓋餘夢鑰壓) 更多
NCT04899349 (CTgov)	临床2期	晚期乳腺癌 \| 乳腺癌	2	Fulvestrant+Alpelisib+Dapagliflozin+Metformin XR+Dapagliflozin + metformin XR (Alpelisib + Fulvestrant + Dapagliflozin + Metformin XR)	糧鑰網夢觸製網鑰窪餘(簾範簾夢鬱蓋鹽範觸壓) = 糧廠獵衊願顧窪壓選遞範齋鬱遞鑰壓糧蓋鏇壓 (鹽網製鏇積襯鹽齋構廠, 廠觸糧蓋餘廠繭蓋餘淵 ~ 衊構齋顧壓糧鹹淵製膚) 更多	-	2023-12-12
				Fulvestrant+Alpelisib+Metformin XR (Alpelisib + Fulvestrant + Metformin XR)	選廠壓鹹網醖鬱襯鑰鏇(齋廠窪網餘鑰鹹夢淵壓) = 夢憲鏇範糧窪獵鬱膚積膚壓積襯網蓋選選願遞 (選餘艱選窪壓遞艱衊願, 鏇積鬱蓋醖範壓襯築襯 ~ 膚糧遞餘遞齋獵鑰廠艱) 更多