克拉屈滨(Cladribine) - 药物靶点：RNR_在研适应症：多发性硬化症，复发性多发性硬化，贫血_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(2R,3S,5R)-5-(6-amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol、2-Chloro-2'-deoxy-beta-adenosine、2-Chloro-2'-deoxyadenosine

+ [24]

靶点

RNR

作用机制

RNR抑制剂(核糖核苷酸还原酶复合体抑制剂)

治疗领域

肿瘤免疫系统疾病神经系统疾病+ [2]

在研适应症

多发性硬化症复发性多发性硬化贫血+ [7]

非在研适应症

原研机构

在研机构

+ [6]

非在研机构

EMD Serono Research & Development Institute, Inc.

Janssen Pharmaceuticals, Inc.

Chord Therapeutics SA初创企业

+ [1]

最高研发阶段批准上市

首次获批日期

美国 (1993-02-26),

毛细胞白血病

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)、孤儿药 (欧盟)、孤儿药 (日本)

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结构

分子式C10H12ClN5O3

InChIKeyPTOAARAWEBMLNO-KVQBGUIXSA-N

CAS号4291-63-8

关联

159

项与克拉屈滨相关的临床试验

NCT06232655 / Not yet recruiting临床2期IIT

Study of Cladribine+Venetoclax After Failure of Venetoclax+Hypomethylating Agent in Monocytic AML

Investigation of Relapsed or refractory AML with a monocytic phenotype after failure of hypomethylating agent+venetoclax

开始日期2024-12-01

申办/合作机构

University of Colorado Denver

[+1]

NCT06463587 / Not yet recruiting临床3期

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm, 3-Period Study to Assess the Efficacy and Safety of a New Formulation of Oral Cladribine Compared With Placebo in Participants With Generalized Myasthenia Gravis(MyClad)

The purpose of this clinical study is to determine the efficacy and safety of a new oral cladribine formulation in participants with Generalized Myasthenia Gravis (gMG) in comparison to placebo. It will also investigate the sustained efficacy, the need for retreatment, and the long-term safety of oral cladribine in gMG. An additional component is included to characterize the Pharmacokinetics (PK) of the new cladribine formulation in gMG participants. This study is divided into 3 periods: the double-blind placebo control (DBPC) pivotal period, and 2 extensions, the blinded extension (BE) and the retreatment (RT) period.

开始日期2024-06-17

申办/合作机构

Merck Healthcare KGaA

[+1]

NCT05766514 / Not yet recruiting临床2期IIT

Phase II Prospective Randomized Control Trial of Cladribine and Low-Dose Cytarabine (LoDAC) Alternating With Decitabine vs. Hypomethylating Agents (HMA) Plus Venetoclax as Frontline Therapy for AML or High-Grade MDS in Patients Unfit for Intensive Induction

This phase II, open-label, randomized trial will compare the efficacy of the novel regimen of cladribine/low-dose cytarabine alternating with decitabine to the current standard of care regimen of hypomethylating agents (decitabine or azacytidine) plus venetoclax in elderly and unfit patients presenting with AML or high grade MDS for whom targeted therapy based on the molecular/genetic subtype is not available. Subjects will be randomized to be treated with either cladribine/low-dose cytarabine alternating with decitabine (Arm A) or decitabine or azacitadine plus venetoclax (Arm B).

开始日期2024-06-01

申办/合作机构

University of Florida

100 项与克拉屈滨相关的临床结果

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100 项与克拉屈滨相关的转化医学

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100 项与克拉屈滨相关的专利（医药）

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3,612

项与克拉屈滨相关的文献（医药）

2024-02-01·Multiple sclerosis and related disorders

Quantifying the administration and monitoring time burden of several disease-modifying therapies for relapsing multiple sclerosis in the United Kingdom: A time and motion study

Article

作者: Amin, Amerah ; De Cock, Erwin ; Ashton, Luke ; Pendlebury, Jessica ; Lowndes, Claire ; Kalra, Seema ; Leclerc, Stephanie ; Evans, Hannah ; Brownlee, Wallace ; Carod-Artal, Francisco Javier ; Barker, Noreen ; Rog, David

BACKGROUND:

The treatment landscape for relapsing multiple sclerosis (MS) has changed dramatically in recent decades, including an increasing number of high-efficacy disease-modifying therapies (DMTs) with varied administration and monitoring requirements. Coupled with greater focus on earlier treatment, these factors have resulted in stretching of the capacity of MS specialist services and allied healthcare professionals (HCPs). To assist with the effective planning of MS services in the UK NHS, this study quantified the administration and monitoring time burden associated with high-efficacy DMTs (alemtuzumab, cladribine tablets, fingolimod, natalizumab, and ocrelizumab) for relapsing MS.

METHODS:

A Time and Motion (T&M) study was conducted across four MS centres in the UK, over 3-4 months per centre (Aug 2019-Feb 2021). Time dedicated by HCPs (including but not limited to neurologists, MS specialist nurses, infusion nurses, and healthcare assistants) to pre-specified drug administration and monitoring activities, elicited during pre-study interviews at each centre, was assessed for each of the selected DMTs. Administration activities included: installing peripheral access; pre-medication administration (if needed); preparing drug for infusion; infusion initiation, monitoring, and disconnection; and patient monitoring post-infusion. Monitoring activities included: booking appointments for blood draws; blood draw; retrieval and review of blood results; maintaining blood records and follow-up with the patient; checking availability of MRI results and follow-up with the patient; booking appointments for neurologist or nurse consultations; and checking patient files prior to clinic visits. A T&M model was built using observational T&M study results, data obtained through pre-study interviews, as well as stipulated monitoring intervals from relevant Summaries of Product Characteristics for the selected DMTs, to estimate active HCP time with each DMT, extrapolated over a period of 4 years per-patient.

RESULTS:

For oral DMTs, projected total active HCP time (monitoring only) per-patient over 4 years was 14.7 h for cladribine tablets and 19.2 h for fingolimod. For infused DMTs, total time (administration and monitoring) for alemtuzumab was 37.7 h (6.0 and 31.6 h, respectively), 48.1 h for natalizumab (17.4 and 30.8 h, respectively), and 23.5 h for ocrelizumab (6.1 and 17.4 h, respectively).

CONCLUSIONS:

While active HCP time varied across centres, infused DMTs were projected to require the greatest amount of HCP time associated with administration and monitoring over 4 years versus oral DMTs. These findings may assist MS-specific HCPs in planning and delivering the equitable provision of DMT services for patients with relapsing MS.

2024-02-01·Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

Incidence of SARS-CoV-2 infection in patients with multiple sclerosis who received SARS-CoV-2 vaccines and are under treatment with high-efficacy therapies in Argentina

Article

作者: Pestchanker, Claudia ; Burgos, Marcos ; Pappolla, Agustín ; Alonso, Ricardo ; Garcea, Orlando ; Deri, Norma ; Silva, Berenice ; Alonso Serena, Marina ; Rojas, Juan I ; Patrucco, Liliana ; Marrodan, Mariano ; Federico, Belén ; Carnero Contentti, Edgar ; Tkachuk, Verónica ; Alvez Pinheiro, Amelia ; Balbuena, María E ; Giunta, Diego ; Tavolini, Darío ; Zanga, Gisela ; Cabrera, Mariela ; Luetic, Geraldine ; Hryb, Javier ; Correale, Jorge ; Vrech, Carlos ; Fernandez Liguori, Nora ; Nofal, Pedro ; Cristiano, Edgardo ; Ysrraelit, María Célica ; López, Pablo A ; Carrá, Adriana

METHODS:

Non-interventional, retrospective cohort study that collected information directly from RelevarEM. Adult PwMS who had been treated for at least 6 months with a HET (ocrelizumab, natalizumab, alemtuzumab, cladribine) who had received at least two doses of SARS-CoV-2 vaccines available in Argentina were included. Full course of vaccination was considered after the second dose of the corresponding vaccines. Cumulative incidence of SARS-CoV-2 infection was reported for the whole cohort by Kaplan-Meier survival curves (which is expressed in percentage) as well as incidence density (which is expressed per 10.000 patients/day with 95% CI).

RESULTS:

Two hundred twenty-eight PwMS were included. Most frequent first and second dose received was AstraZeneca vaccine, followed by Sputnik vaccine. Most frequent HETs used in included patients were cladribine in 79 (34.8%). We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina. We described the incidence rate after vaccination for every HET used, it being significantly higher for ocrelizumab compared with other HETs (p = 0.005). Only five patients presented a relapse during the follow-up period with no differences regarding the pre-vaccination period.

CONCLUSIONS:

We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina.

2024-02-01·Multiple sclerosis and related disorders

Neutropenia following immune-depletion, notably CD20 targeting, therapies in multiple sclerosis

Review

作者: Kang, Angray S ; Giovannoni, Gavin ; Baker, David ; Schmierer, Klaus

Neutropenia serves as a risk factor for severe infection and is a consequence of some immune-depleting immunotherapies. This occurs in people with multiple sclerosis following chemotherapy-conditioning in haematopoietic stem cell transplantation and potent B cell targeting agents. Whilst CD52 is expressed by neutrophils and may contribute to early-onset neutropenia following alemtuzumab treatment, deoxycytidine kinase and CD20 antigen required for activity of cladribine tablets, off-label rituximab, ocrelizumab, ofatumumab and ublituximab are not or only weakly expressed by neutrophils. Therefore, alternative explanations are needed for the rare occurrence of early and late-onset neutropenia following such treatments. This probably occurs due to alterations in the balance of granulopoiesis and neutrophil removal. Neutrophils are short-lived, and their removal may be influenced by drug-associated infections, the killing mechanisms of the therapies and amplified by immune dyscrasia due to influences on neutropoiesis following growth factor rerouting for B cell recovery and cytokine deficits following lymphocyte depletion. This highlights the small but evident neutropenia risks following sustained B cell depletion with some treatments.

75

项与克拉屈滨相关的新闻（医药）

2024-06-25

·Firstwordpharma

Merck KGaA’s latest pipeline woes place more urgency on deals

Merck KGaA’s shares fell as much as 10% on Tuesday as the latest late-stage failure – this time for xevinapant – raised more questions over the company’s pharmaceutical pipeline and its ability to meet growth targets. "This is (another) surprising setback for the healthcare pipeline. We continue to like the Merck story, but concede the company will need to rebuild credibility regarding its pipeline prowess," Barclays analysts remarked.Xevinapant – which Merck in-licensed from Debiopharm – was being studied in the Phase III TrilynX and X-Ray Vision trials for patients with head and neck squamous cell carcinoma (HNSCC). The company said Monday that both studies would be discontinued after an interim analysis determined that TrilynX was unlikely to meet its primary endpoint of improving event-free survival. The inhibitor-of-apoptosis proteins (IAP) antagonist was Merck’s lead oncology pipeline asset and its failure follows a similar fate for the BTK inhibitor evobrutinib in multiple sclerosis in March. Following the two setbacks, analysts at Stifel Nicolaus said Merck “has little to show for internal and externally licensed R&D that are supposed to shoulder some Mavenclad/Cladribine expiry in 2027.”Larger deals likelyMeanwhile, analysts at Morgan Stanley noted that “whilst xevinapant was not key to our investment thesis, this headline further challenges the growth outlook of the healthcare business,” adding “there is now likely more debate on how to reinvigorate R&D at [the] healthcare business, which continues to weigh on shares.” Merck had pinned its hopes on the success of evobrutinib and xevinapant in helping the healthcare segment achieve growth in the mid-single-digit percentage range over the medium term.Morgan Stanley analysts also noted that while “Merck's management believes that the healthcare business could still grow even without xevinapant… we believe Merck may now be more likely to reallocate capital to larger healthcare deals in order to rebuild the pipeline.” In March, the pharma’s CEO Belén Garijo said that moving forward, more than 50% of its drug launches are expected to come from external innovation, adding that deals “allow us to pick the desired assets to complement our portfolio.”

临床3期

2024-06-20

·米内网

【关注】14亿注射剂，四川药企过评了

精彩内容 6月20日，汇宇制药公告称，公司（含子公司）申报的两款4类仿制药获批生产并视同过评，分别为醋酸奥曲肽注射液、尼莫地平注射液。米内网数据显示，这2款注射剂2023年在中国公立医疗机构终端的销售额分别超过14亿元、3亿元。奥曲肽是人工合成的天然生长抑素的八肽衍生物，其药理作用与生长抑素相似，对生长激素(GH)、胰高血糖素和胰岛素的抑制作用比生长抑素更强。醋酸奥曲肽注射液适用于控制手术治疗或放射治疗不能充分控制病情的肢端肥大症患者的症状并降低患者的生长激素(GH)和胰岛素样生长因子-1(IGF-1)血浆水平；缓解与功能性胃肠胰腺(GEP)内分泌肿瘤有关的症状；预防胰腺手术后并发症；肝硬化患者胃-食管静脉曲张所致出血的紧急治疗等。醋酸奥曲肽注射液已被纳入第七批国采，近年来在中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院（简称中国公立医疗机构）终端的销售额有所下滑，但2023年仍有超14亿元的销售规模，其中原研厂家诺华占主导地位，但市场份额逐渐被蚕食。近年来中国公立医疗机构终端醋酸奥曲肽注射液销售情况（单位：万元）来源：米内网中国公立医疗机构药品终端竞争格局尼莫地平为1，4-二氢吡啶类钙拮抗剂，具有高度亲脂性，容易穿透血脑屏障。尼莫地平注射液可用于预防和治疗动脉瘤性蛛网膜下腔出血后脑血管痉挛引起的缺血性神经损伤。该产品2023年在中国公立医疗机构终端的销售额超过3亿元，其中原研厂家拜耳主导市场。尼莫地平注射液暂未纳入国采，目前已有济川药业、海南普利制药、北京柏雅联合药物研究所、北京百美特生物、辽宁亿帆药业、广东科伦药业、四川汇宇制药7家企业的产品过评或视同过评，已满足国采初步入围条件。汇宇制药表示，公司研发的醋酸奥曲肽注射液、尼莫地平注射液通过仿制药一致性评价，提升了自身的竞争能力，对公司的发展起到积极作用。米内网数据显示，2024年以来，汇宇制药有6个品种获批生产并视同过评，均为注射剂，其中有3个为抗肿瘤和免疫调节剂，消化系统及代谢药、全身用激素类制剂(不含性激素和胰岛素)、心脑血管系统药物各有1个。 2024年以来汇宇制药获批上市的品种来源：米内网中国申报进度（MED）数据库 6个品种中，甲氨蝶呤注射液、克拉屈滨注射液为国产第2家获批；注射用盐酸罗沙替丁醋酸酯、醋酸奥曲肽注射液2023年在中国公立医疗机构终端的销售额均超过10亿元。资料来源：米内网数据库、公司公告等注：米内网《中国公立医疗机构药品终端竞争格局》，统计范围是：中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院，不含民营医院、私人诊所、村卫生室；上述销售额以产品在终端的平均零售价计算。数据统计截至6月20日，如有疏漏，欢迎指正！本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 【分享、点赞、在看】点一点不失联哦

上市批准一致性评价放射疗法

2024-06-17

·Pharma CMC

76个新批件！16个一致性评价受理号今日获批：首家、第二家

限时免费报名中刚刚，NMPA发布2024年06月17日药品批准证明文件送达信息，本批次共有76个受理号获批，其中16个为一致性评价受理号，过评品种包括：北京斯利安药业有限公司，叶酸片江苏恩华药业股份有限公司、成都天台山制药股份有限公司，盐酸戊乙奎醚注射液昆明积大制药股份有限公司，盐酸坦索罗辛缓释片瀚晖制药有限公司，克拉屈滨注射液等其中，昆明积大制药的盐酸坦索罗辛缓释片为国内首家过评，用于治疗因前列腺增生所致的排尿障碍等症状，如尿频，夜尿增多、排尿困难等。瀚晖制药的克拉屈滨注射液为国内第二家过评，用于经干扰素治疗失败后活动性的伴有临床意义的贫血、中性粒细胞减少、血小板减少以及疾病相关症状的毛细胞白血病（HCL）治疗。今年5月，汇宇制药的克拉屈滨注射液以化学药品3类申报，按照与参比制剂质量和疗效一致的技术要求审评并获批，视同通过仿制药质量和疗效一致性评价，为国内首家。欢迎添加微信，进入批件之家（实名制）仅供交流，与官方无关

一致性评价

100 项与克拉屈滨相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01370	克拉屈滨	L04AA40 L01BB04	DB00242

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
多发性硬化症	美国	EMD Serono, Inc.	2019-03-29
复发性多发性硬化	欧盟	Merck Europe BV	2017-08-22
复发性多发性硬化	冰岛	Merck Europe BV	2017-08-22
复发性多发性硬化	列支敦士登	Merck Europe BV	2017-08-22
复发性多发性硬化	挪威	Merck Europe BV	2017-08-22
贫血	中国	瀚晖制药有限公司	2005-11-15
中性粒细胞减少	中国	瀚晖制药有限公司	2005-11-15
血小板减少症	中国	瀚晖制药有限公司	2005-11-15
套细胞淋巴瘤	日本	Clinigen KK	2002-12-16
非霍奇金淋巴瘤	日本	Clinigen KK	2002-12-16
毛细胞白血病	美国	Janssen Pharmaceuticals, Inc.	1993-02-26

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
重症肌无力	临床3期	美国	Merck Healthcare KGaA	2024-06-17
重症肌无力	临床3期	德国	Merck Healthcare KGaA	2024-06-17
复发-缓解型多发性硬化	临床3期	-	EMD Serono, Inc.	2005-04-01
急性髓性白血病	临床2期	美国	University of Colorado Denver	2024-12-01
视神经脊髓炎	临床前	瑞士	Chord Therapeutics SA初创企业	2020-06-01

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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


NCT04776213 (CTgov)	临床4期	复发性多发性硬化	280	Mavenclad®	構獵鹹衊壓淵夢鑰鏇製(艱鑰鏇糧鹽製遞糧鹽淵) = 艱鏇餘顧餘獵鏇醖鏇鏇鑰淵積衊構醖憲繭積憲 (構鹹鹹鹹鑰鏇壓襯糧襯, 齋衊夢艱襯網遞淵鹽範 ~ 鹽積醖憲窪遞選鏇獵網) 更多	-	2024-05-28
ASCO2024	N/A	-	-	Cladribine	積壓壓網積範鹽鹽顧遞(網鹽衊膚願鑰鹹選衊簾) = TRM, nausea and acute GvHD frequency was lower with cladribine (p=0.35, p=0.001 and p=0.02, respectively). Typhilitis and perianal infections were more common with cladribine (p=0.07 and p=0.04, respectively) 衊獵繭憲鹽蓋鏇蓋網膚 (醖獵積醖顧鹽糧構簾齋 )	-	2024-05-24
				Fludarabine
EHA2024	N/A	毛细胞白血病 BRAF V600E mutation	7	Cladribine monotherapy	窪鏇壓積夢築獵願願糧(顧齋壓鹽構壓網觸願繭) = Complete remission was obtained in all pts 蓋網製簾構簾製觸願觸 (網淵廠鏇鬱構糧窪醖遞 ) 更多	积极	2024-05-14
EHA2024	N/A	复发性急性髓细胞白血病	-	Cladribine 5 mg/m2 IV	繭醖願憲醖鑰衊獵築窪(築選遞繭鹽製糧壓願鹽) = 8% 淵蓋繭觸襯醖蓋憲糧廠 (積鏇蓋繭獵鏇醖蓋蓋遞 ) 更多	-	2024-05-14
				Cytarabine 1g/m2 IV
NCT01439750 (AACR2024) 人工标引	临床1期	套细胞淋巴瘤	13	velcade + cladribine+ rituximab	醖衊鏇餘憲齋襯襯衊膚(糧遞鹹遞襯簾衊鹹網鹹) = No subject experienced dose limited toxicity (DLT) at either level 1 or 2, one possible DLT (infectious colitis) was observed on a subject during 2nd cycle at level 3. Then no additional DLTs were seen in 3 subjects added to level 3 廠艱艱願繭網壓餘鑰築 (醖顧範顧窪艱憲憲鏇鏇 ) 更多	积极	2024-04-05
ACTRIMS2024	N/A	-	-	Natalizumab	選繭鏇鹽窪鏇醖遞鬱衊(餘蓋鹹積積鹽襯獵築願) = The therapy was well tolerated, with COVID-19, nausea, and headache among the most common adverse events 蓋淵蓋餘鑰鏇繭淵淵夢 (壓廠簾壓齋獵獵艱鹹製 )	-	2024-03-01
				Cladribine tablets
ACTRIMS2024	N/A	多发性硬化症	847	Cladribine Tablets	鬱廠願糧鏇鬱鏇範襯網(鏇繭繭夢夢範製製鏇蓋) = 憲觸構築願製淵網積構遞憲衊構鏇窪鏇憲醖顧 (鬱遞簾壓選願製鑰艱鹽 ) 更多	积极	2024-03-01
				Cladribine Tablets	鬱廠願糧鏇鬱鏇範襯網(鏇繭繭夢夢範製製鏇蓋) = 膚鑰願繭餘廠夢壓壓醖遞憲衊構鏇窪鏇憲醖顧 (鬱遞簾壓選願製鑰艱鹽 )
ACTRIMS2024	N/A	S1P (Sphingosine-1-phosphate) receptor modulators	111	Cladribine tablets (CladT)	鏇餘網蓋鏇廠觸憲鏇淵(簾遞觸鏇獵淵製壓醖襯) = 遞鹽願壓製鹽襯積鏇簾鏇製鹹獵觸壓齋餘餘憲 (觸積簾製醖蓋鏇積襯繭 ) 更多	积极	2024-03-01
				Sphingosine-1-phosphate (S1P) receptor modulators	鏇餘網蓋鏇廠觸憲鏇淵(簾遞觸鏇獵淵製壓醖襯) = 鏇觸選衊鬱顧壓鏇衊鑰鏇製鹹獵觸壓齋餘餘憲 (觸積簾製醖蓋鏇積襯繭 )
ACTRIMS2024	N/A	继发进展型多发性硬化	4	Oral Cladribine	廠餘繭蓋網襯製餘願積(衊觸艱顧鬱衊鏇網網襯) = 衊齋簾醖鹽鏇夢壓醖鏇積鏇願餘遞鏇製鬱糧糧 (積顧襯淵觸網選廠鑰齋 )	积极	2024-03-01
				High-efficacy DMT (e.g. ocrelizumab, siponimod)	廠餘繭蓋網襯製餘願積(衊觸艱顧鬱衊鏇網網襯) = 鹽遞窪簾遞積襯製蓋淵積鏇願餘遞鏇製鬱糧糧 (積顧襯淵觸網選廠鑰齋 )
ACTRIMS2024	N/A	多发性硬化症	-	Cladribine tablets 3.5mg/kg	選醖積鑰窪積鏇艱鹽廠(範鑰鬱淵鬱鬱壓構構構) = 鬱範選鹹夢窪積積積獵淵衊鏇網壓襯糧範夢鬱 (顧願鬱窪憲餘壓鹽淵憲 ) 更多	积极	2024-03-01