——新型抗凝剂Praxbind(idarucizumab)获批准用于特异性紧急情况
2015年11月27日，德国制药巨头勃林格殷格翰研发的新型抗凝剂获欧盟委员会（EC）已批准单抗药物Praxbind（idarucizumab），用于快速且特异性地逆转新型口服抗凝血剂Pradaxa（品牌名：泰毕全，通用名：dabigatran etexilate，达比加群酯）的抗凝作用。Praxbind适用于接受抗凝血剂Pradaxa（达比加群酯）治疗的患者，在急诊手术、介入性操作或出现危及生命或无法控制的出血并发症，需要逆转Pradaxa的抗凝作用时使用。
此次批准，也标志着Praxbind成为欧盟用于一种非维生素K拮抗剂口服抗凝剂（NOAC）的首个特异性逆转剂。之前，Praxbind在美国监管方面收获了突破性药物资格及优先审查资格，并于2015年10月中旬获得FDA加速批准。
新型口服抗凝血剂Pradaxa（达比加群酯）的抗凝作用可以挽救许多患者的生命，但在某些情况下医生也需要迅速逆转该药的抗凝效果。当患者因使用Pradaxa（达比加群酯）而出现不可控制的出血等紧急情况时，Praxbind可作为速效逆转剂，该药的上市，将为临床医生及患者在选择Pradaxa治疗时增添信心。
勃林格殷格翰心血管药物治疗领域副总裁Jorg Kreuzer教授表示：“我们非常高兴能为欧洲的患者及临床医生提供新型口服抗凝药Pradaxa（达比加群酯）的首个特异性逆转剂——Praxbind。正如多年前公司推出Pradaxa（达比加群酯）一样，此次Praxbind成功获批，意味着勃林格殷格翰又一次引领了抗凝治疗领域的进步。尽管我们预期临床实践中会很少用到Praxbind，但该药的上市，将增加医生和患者选择Pradaxa（达比加群酯）的信心。”
Praxbind的获批，是基于来自健康志愿者的数据以及RE-VERSE AD临床试验的期中分析数据。这些研究证实Praxbind可迅速逆转Pradaxa（达比加群酯）的抗凝效应，在给予5克剂量的Praxbind几分钟内就能立即见效。在几乎所有患者中，Praxbind能够完全逆转Pradaxa（达比加群酯）的抗凝作用，并且能够持续至少12小时。研究中，没有发现与Praxbind相关的严重不良反应事件及促凝信号

Praxbind® (idarucizumab) approved in European Union for the specific reversal of Pradaxa® (dabigatran etexilate)
• Idarucizumab is the first specific reversal agent for a NOAC to receive European approval
• idarucizumab immediately reverses the anticoagulant effect of dabigatran
About the idarucizumab Clinical Trial Programme
Idarucizumab was discovered and developed by Boehringer Ingelheim scientists. The research programme was initiated in 2009,1 before dabigatran (Pradaxa®) was launched in the U.S. in 2010.9
The company completed three phase I trials of idarucizumab in human volunteers and is continuing to evaluate idarucizumab in RE-VERSE AD™ (NCT 02104947, EudraCT 2013‐4813‐41), a phase III global study that includes patients taking dabigatran who require emergency procedures or have uncontrolled bleeding.2-4,7 The study is the first of its kind in patients, and has been underway since May 2014, enrolling patients in more than 35 countries.10 The RE-VERSE AD™ global phase III patient study is ongoing to capture further data on the efficacy and safety profile of idarucizumab.
About idarucizumab
Idarucizumab is a humanized antibody fragment, or Fab, designed as a specific reversal agent to dabigatran.11 Idarucizumab binds specifically to dabigatran molecules only, neutralising their anticoagulant effect without interfering with the coagulation cascade.11,12 Idarucizumab is approved for use in adult patients treated with dabigatran when rapid reversal of its anticoagulant effects is required for emergency surgery / urgent procedures or in life-threatening or uncontrolled bleeding.1
Regulatory reviews and submissions in other countries are ongoing.1 Idarucizumab is the only specific reversal agent for a NOAC currently in regulatory review.1 Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.1
About dabigatran etexilate
Clinical experience of dabigatran equates to more than 5 million patient-years in all licensed indications worldwide.1 Dabigatran has been in the market for more than 7 years and is approved in over 100 countries.
New Drugs Online Report for idarucizumab
Information
Generic Name: idarucizumab  
Trade Name: Praxbind 
Synonym: BI 655075 
Entry Type: New molecular entity  
Development and Regulatory status
UK: Launched 
EU: Launched 
US: Approved (Licensed) 
UK launch Plans: Available only to registered users
Actual UK launch date: December 2015 
Comments
Dec 15: Launched in the UK on 17 Dec. Price of one dose (2 x 2.5g/50mL vials) is £2,400 [15].
14/12/2015 10:37:38 
Nov 15: Approved in EU. Boehringer Ingelheim will launch idarucizumab in EU countries as soon as possible [14].
27/11/2015 12:11:01 
Oct 15: Approved in the US [13].
19/10/2015 17:45:14 
Sep 15: EU positive opinion for use as a specific reversal agent for dabigatran and is indicated in adults treated with Pradaxa (dabigatran etexilate) when rapid reversal of its anticoagulant effects is required: For emergency surgery/urgent procedures; and in life-threatening or uncontrolled bleeding. It is proposed that Praxbind be restricted to hospital use only [12].
25/09/2015 12:54:18 
Apr 15: FDA grants priority review for idarucizumab. Idarucizumab will be reviewed under the FDA´s Accelerated Approval process [7]. 
24/04/2015 08:47:29 
Mar 15: Boehringer Ingelheim files idarucizumab for approval in the US, EU and Canada for use in patients requiring an antidote to dabigatran. The submissions also include first interim data from the ongoing PIII RE-VERSE ADTM study, assessing idarucizumab in patients treated with dabagatran who are in need of emergency intervention, or experience an uncontrolled or life-threatening bleeding event [6].
04/03/2015 11:28:04 
Jun 14: US FDA grants breakthrough therapy designation to idarucizumab [2].
27/06/2014 11:51:39 
Trial or other data
It is the first NOAC reversal agent to be reviewed. Currently, no NOACs have an approved reversal agent [7]. An editorial Published in the NEJM, discusses the potential place in therapy of the targeted anti-anticoagulants" [11]. 
28/09/2015 14:41:35
Jun 15: Boehringer Ingelheim announced positive results from PIII RE-VERSE AD (NCT02104947) clinical trial. The study shows that 5g of idarucizumab almost immediately reversed the anticoagulant effect of dabigatran in pts who needed it under emergency situations. Study results were also published in The New England Journal of Medicine and authors concluded that “Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes.” The study was designed to look at different pts and real-world emergency situations. This interim analysis included 90 pts who received idarucizumab (51 patients in group A and 39 in group B). Pts in gp A had uncontrolled or life-threatening bleeding complications (e.g. intracranial haemorrhage or severe trauma) and pts in gp B needed emergency surgery or an invasive procedure. Based on laboratory analysis of dilute thrombin time, the median maximum % reversal of the anticoagulant effect within 4 hours was 100% (95% confidence interval, 100 to 100). One thrombotic event occurred within 72hrs after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated [9,10].
23/06/2015 09:53:23
Jun 15: Results of PI trial NCT01688830 published in The Lancet [8].
19/06/2015 15:34:23
Dec 14: PI data reported showing administration of idarucizumab in healthy volunteers who were middle-aged (45 to 64 years) or elderly (65 to 80 years), or volunteers with mild or moderate kidney impairment (n=46) resulted in immediate, complete and sustained reversal of the anticoagulation effects of dabigatran. Anticoagulation was restored when volunteers were re-dosed with dabigatran 24 hours after idarucizumab was administered [5].
15/12/2014 10:55:37
Nov 14: New data on idarucizumab show it can reverse the effect of dabigatran etexilate on both blood coagulation and the blood clotting mechanism in a PI study in 35 healthy volunteers [4].
20/11/2014 11:41:06
Apr 14: NCT02104947 is a PIII case series study of the reversal of the anticoagulant effects of dabigatran over 4 hours by 5g idarucizumab IV in 250 patients treated with dabigatran etexilate who have uncontrolled bleeding or require emergency surgery or procedures. The study starts Apr 14 and is due to complete Jul17 [1]
15/04/2014 10:34:38
Evidence Based Evaluations
LMEN  http://www.medicinesresources.nhs.uk/en/Communities/NHS/SPS-E-and-SE-England/LNDG/London-Wide-Reviews/LMEN-Summary-of-antidotes-to-NOACs-inlcuding-those-currently-in-development-which-could-impact-NOAC-use-in-the-future/ 
NIHR HSRIC  http://www.hsric.nihr.ac.uk/topics/idarucizumab-for-the-reversal-of-anticoagulation-due-to-treatment-with-dabigatran-first-line/ 
EPAR  http:
References  
Available only to registered users
 Category
BNF Category: Anticoagulants and protamine (02.08)
Pharmacology: Fully humanised monoclonal antibody fragment which has a highly specific binding affinity with dabigatran therefore reversing any anticoagulant activity of dabigatran and its metabolites.  
Epidemiology: Across several trials assessing the use of dabigatran against enoxaparin, warfarin or placebo for various indications in relation to venous thromboembolism, the percentage of patients experiencing any bleeding event ranged from 10.5% to 19.4% and included minor bleeding events in the range of 13.2% to 14.9% and major bleeding events in the range 0.3% to 3.3% [3].  
Indication: Anticoagulation reversal 
Additional Details: in patients taking dabigatran – required for life-threatening or uncontrolled haemorrhage, or emergency surgery/procedures; first line.  
Method(s) of Administration  
Intravenous 
Company Information
Name: Boehringer Ingelheim 
US Name: Boehringer Ingelheim 
Further Information
Anticipated commissioning route (England) CCG 
High cost drug list? Awaiting Update
Tariff Likely HRG included
Implications Available only to registered users