2015年11月26日,欧盟委员会（EC）已批准Elocta（rFVIIIFc）用于A型血有病患者的治疗。此次批准适用于欧盟所有28个成员国。双方预计在2016年初将Elocta推向欧洲市场。
Elocta是一种重组的因子VIII Fc融合蛋白，具有延长的半衰期，该药将成为欧盟首个每3-5天预防性用药可针对出血事件提供长期保护的A型血有病药物。
Elocta适用于所有年龄段A型血有病患者的按需治疗和预防性治疗。此次批准，基于关键III期A-LONG研究和III期Kids A-LONG研究的数据。前一项研究证明了Elocta在既往未接受治疗的12岁及以上严重A型血有病患者中的疗效、安全性和药代动力学，后一项研究证明了Elocta在既往未接受治疗的12岁以下A型血有病患者中的疗效、安全性。
目前，Sobi和百健合作开发及商业化rFVIIIFc用于A型血有病的治疗。去年，Sobi行使了选择权，承担rFVIIIFc在指定地区的最后开发及商业化，主要包括欧洲、北非、俄罗斯及中东地区的其他国家。百健将负责产品的开发及生产，同时拥有在北美及Sobi所负责区域以外的国家和地区的商业化。在Sobi负责区域内，rFVIIIFc的品牌名为Elocta；而在美国、加拿大、澳大利亚、新西兰及日本，rFVIIIFc已获批以品牌名Eloctate上市销售。
Elocta是首个具有延长的循环半衰期的重组凝血因子VIII产品，该药的适应症为：用于儿童和成人A型血友病患者出血事件的控制和预防，围术期管理和常规预防。Eloctate不适用于血管性血友病（von Willebrand disease）的治疗。Eloctate是通过将删除了B-结构域的凝血因子VIII与免疫球蛋白G亚类1——IgG1的Fc部位融合而获得，可利用一种天然存在的通路，延长药物在体内的时间。尽管Fc融合技术已使用超过15年，但百健是首个将其应用于血友病治疗的公司。
New Drugs Online Report for efmoroctocog alfa
Information
Generic Name: efmoroctocog alfa  
Trade Name: Elocta (EU), Eloctate 
Synonym: rFVIIIFc, BIIB031; Factor VIII-Fc; Long-lasting factor VIII fusion protein;efraloctocog alfa  
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: January 2016 
Comments
Dec 15: Will be launched in the UK on 4 Jan 2016 [18].
21/12/2015 08:46:13 
Nov 15: Approved in EU [17].
25/11/2015 09:51:04 
Sep 15: EU positive opinion for treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). Elocta can be used for all age groups [16].
25/09/2015 12:37:13 
Nov 14: The EMA has accepted an application seeking approval of Elocta for treatment of haemophilia A. The application includes results from the A-LONG and Kids A-LONG PIII studies [14].
06/11/2014 10:54:18 
Jun 14: Approved in the US [13].
09/06/2014 16:37:04 
Nov 13: Launch of Eloctate in the US will be delayed until mid-2014 after the FDA requested additional information on how manufacturing data are collected and reported. The US delay is not expected to have on the drug´s anticipated approval in Europe [11].
13/11/2013 09:42:45 
Mar 13: Filed in the US [9]
13/03/2013 12:50:55 
Oct 12: The company plans to file in the US 1H 2013. Consistent with EMA guidelines that require a study in children < 12 years of age prior to filing, filing in the EU is expected on completion of the ongoing Kids A-LONG study [7].
01/11/2012 12:30:47 
Sep 10: granted orphan designation in the EU (EU/3/10/783) [6]
29/10/2012 14:32:35 
Dec 10: Granted orphan drug status in the US [2].
29/12/2010 13:27:38 
Jul 10: Companies plan to start a PIII study [1].
21/07/2010 18:05:33 
Trial or other data
Aug 15: Biogen & SOBI announce interim data from the PIII extension ASPIRE study (published in Haemophilia). Study participants completing the PIII A-LONG and Kids A-LONG studies were eligible to participate in ASPIRE. The results to-date show most participants in ASPIRE, maintained or extended their dosing intervals between treatments compared to the A-LONG and Kids A-LONG studies. Median time in the ASPIRE study was 80.9 weeks for adults and adolescents completing the A-LONG study, and 23.9 weeks for children completing the Kids A-LONG study. Inhibitor development is the primary endpoint of ASPIRE and no inhibitors were reported in any treatment groups. Through the interim ASPIRE analysis, adults and adolescents experienced annualized bleeding rates (ABRs) of 0.66, 2.03 and 1.97 in the individualized, weekly and modified prophylaxis arms, respectively. Children on individualized prophylaxis also experienced low bleeding rates, with an overall median ABR of 0.0 in children less than 6 years of age, and 1.54 for children ages 6 to 12. These results were consistent with data from the Phase 3 A-LONG and Kids A-LONG studies. Of the adults and adolescents who had previously been treated prophylactically and who remained in the study through the interim analysis (n=128), 72% maintained their prophylactic dosing interval and 22% lengthened and 6% shortened the time between infusions. Extension study participants could change treatment group at any time. Median cumulative duration of treatment was 117.7 weeks for adults and adolescents, and 51.5 weeks for children less than 12 years old. There were no reports of serious allergic reactions or vascular clots. The most common adverse events (incidence of greater than or equal to 5%) included nasopharyngitis, arthralgia & upper respiratory infection [14].
17/08/2015 10:55:15
Apr 14: Biogen Idec and Swedish Orphan Biovitrum release positive top-line results of the Kids A-LONG PIII study. Eloctate was generally well-tolerated and no inhibitors (neutralizing antibodies that may interfere with the activity of the therapy) were detected. Efficacy analyses showed twice-weekly prophylactic dosing with ELOCTATE maintained low bleeding rates in children. In the study, the relative increase in half-life in children with severe hemophilia A was consistent with the 1.5-fold increase in half-life seen in the A-LONG study of adults and adolescents. Children treated prophylactically with Eloctate had an overall median ABR of 2.0 and a median ABR for spontaneous bleeds of 0.0. Forty-six percent of participants in the study experienced zero bleeding episodes. Overall, ninety three percent of bleeding episodes were controlled by one to two infusions of Eloctate. Additional analyses of the Kids A-LONG study are ongoing, and the companies plan to present detailed results at a future scientific meeting [12].
11/04/2014 10:15:00
Nov 13: The A-LONG study published early online in Blood (13 Nov 2013): doi:10.1182/blood-2013-10-529974
17/11/2013 17:13:30
Feb 13: Further results of the A-LONG study reported. The terminal half-life for rFVIIIFc was 19 hours vs 12 hours for Advate [the most frequently used factor VIII therapy. In addition the mean time for maintaining a clotting factor activity level associated with less bleeding (time to 1%) was ~5 days for rFVIIIFc vs 3.5 days for Advate, and the average rate of clearance was 2.0 mL/hr/kg vs 3.0 mL/hr/kg [8]. 
26/02/2013 10:37:16
Oct 12: Topline results from A-LONG reported. 165 male patients aged ≥12 years were entered into 1 of 3 treatment arms: individualized prophylaxis, weekly prophylaxis and episodic (on-demand) treatment (Arms 1, 2 and 3, respectively). In a subgroup of patients across treatment arms, rFVIIIFc was evaluated in the perioperative management of patients who required a major surgical procedure during the study. 93% of patients completed the study. The median annualized bleeding rates (ABR), including spontaneous and traumatic bleeds, were 1.6, 3.6 and 33.6 in treatment arms 1,2 and 3 respectively. In Arm1, the median dosing interval was 3.5 days. During the last 3 months on study, 30% of patients in arm 1 achieved a mean dosing interval of 5 days. Control of bleeding was assessed in all patients who experienced a bleeding episode during the study. Overall, 98% of bleeding episodes were controlled by 1 or 2 injections of rFVIIIFc. In addition, rFVIIIFc was assessed in the perioperative management of 9 patients undergoing 9 major surgical procedures. Haemostatic efficacy was rated as excellent or good by investigators. Recombinant FVIIIFc was generally well-tolerated. No inhibitors to rFVIIIFc were detected and no cases of anaphylaxis were reported in any patients, all of whom switched from commercially-available Factor VIII products. No serious AEd were assessed to be related to drug by the investigator. The most common AEs (incidence of ≥5%) occurring outside of the perioperative management period were nasopharyngitis, arthralgia, headache and upper respiratory tract infection [7].
31/10/2012 17:12:26
Apr 12: NCT01458106 (Kids ALONG), participant recruitment has not yet started. NCT01181128 (ALONG), estimated completion date Mar 2013 [5].
05/04/2012 17:04:19
Oct 11: NCT01458106 (Kids ALONG) – a PIII open-label, multicentre evaluation of safety, pharmacokinetics, and efficacy of rFVIIIFc, in the prevention and treatment of bleeding episodes in 50 children with Haemophilia A. Subjects will follow either a regimen of PK assessments, followed by a twice weekly prophylactic treatment with rFVIIIFc, or proceed directly to twice weekly prophylactic treatment. Inclusion criteria include: severe haemophilia A defined as <1 IU/dL (<1%), male, <12 years of age and weight ≥13 kg; a history of at least 50 prior exposure days to FVIII and no current, or history of, inhibitor development to FVIII. The primary outcome is frequency of inhibitor development at 30 weeks. The study will start Nov 11 [3].
28/10/2011 11:47:12
NCT01181128 (ALONG): a PII/III open-label, multicentre evaluation of the safety, pharmacokinetics and efficacy of recombinant Factor VIII Fc Fusion (rFVIIIFc) in the prevention and treatment of bleeding in 150 previously treated subjects (aged >11 years) with severe hemophilia A. There will be 3 arms: low dose prophylaxis, high dose prophylaxis and on-demand. There are 2 primary outcomes: Clinically notable changes from baseline in physical examinations, vital signs, lab values, and incidence of AEs and inhibitor development; Annualized number of bleeding episodes (spontaneous and traumatic); both measured over 156 weeks [1].
14/08/2010 18:23:29
Evidence Based Evaluations
NIHR HSRIC  http://www.hsric.nihr.ac.uk/topics/efraloctocog-alfa-eloctate-for-haemophilia-a-in-adults-and-children/ 
EPAR  http:
References  
Available only to registered users
 Category
BNF Category: Anaemias and some other blood disorders (09.01)
Pharmacology: Long-acting, fully-recombinant factor VIII Fc fusion protein  
Epidemiology: Haemophilia A is caused by factor VIII deficiency and occurs in 1 in 5,000 to 1 in 10,000 male live births. Between 50% and 70% of people with haemophilia A have severe disease (<1% factor VIII activity) [4]. There were 5,424 patients with haemophilia A in the UK in 2011 (prevalence 8.7 per 100,000 population), 1,057 were aged 0-13 years [10].  
Indication: Haemophilia A 
Additional Details: prophylaxis and treatment 
Method(s) of Administration  
Intravenous 
Company Information
Name: Swedish Orphan Int AB 
US Name: Biogen Idec (now named Biogen) 
Further Information
Anticipated commissioning route (England) NHSE 
High cost drug list? Yes
Implications Available only to registered users