2014年10月24日,美国食品和药品监督管理局(FDA)昨日批准Obizur[抗血友病因子(重组)，猪序列] 为的治疗出血发作在成年中有获得性血友病A(获得性因子VIII [FVIII]缺乏).
获得性血友病A是一种罕见，但潜在地危及生命，通过(免疫系统蛋白)指向对机体自身F VIII，一种对血液凝固重要蛋白，的抗体发生引起出血疾病当FVIII被这些自身抗体失活，一个人血液不能正常地凝固，导致过量出血可能自发地发生或一个事件例如损伤或手术后发生。
与遗传学血友病不一样，获得性血友病A不是一种遗传疾病而且影响男性和女性。获得性血友病A的发展曾与其他医学情况或健康状态相关，例如妊娠，癌症，或某些药物的使用。但是，大约一半病例，没有可能发现患病原因。这个情况的诊断可能很难和出血严重程度可能使治疗遇到挑战。
FDA生物制品评价和研究中心主任Karen Midthun医学博士说：“批准这个产品为有这个罕见病患者的医护提供一种重要的治疗选择。”
Obizur含一种重组猪FVIII类似物。使用猪FVIII因为它与人FVIII足够相似在血液凝固中有效，但受获得性血友病A人中存在的对作用人FVIII抗体的影响可能较低。
在一项29例获得性血友病A成年临床试验评价Obizur的安全性和疗效，成年接受Obizur治疗严重出血发作。试验证实Obizur在出血发作治疗的有效性。试验中未确定安全性担忧。
Obizur接受FDA孤儿药物指定因为药物一项治疗罕见疾病或情况中使用。
Obizur是由加州西湖村Baxter Healthcare公司制造。
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm420263.htm
FDA Approves Baxter’s OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence], for Acquired Hemophilia A
Approval Based on Data Showing 100% of 28 Patients Responded to Treatment within 24 Hours
DEERFIELD, Ill.--(BUSINESS WIRE)--Baxter International Inc. (NYSE:BAX) today announced that the United States Food and Drug Administration (FDA) has approved OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence] for the treatment of bleeding episodes in adults with acquired hemophilia A (AHA), a very rare and potentially life-threatening acute bleeding disorder. OBIZUR was granted orphan-drug status by the FDA and its review was prioritized based on AHA’s classification as a rare disease and the potential for the treatment to address an important unmet medical need.
OBIZUR is the first recombinant porcine FVIII treatment approved for AHA that allows physicians to manage the treatment’s efficacy and safety by measuring factor VIII activity levels in addition to clinical assessments. OBIZUR replaces the inhibited human factor VIII with a recombinant porcine sequence factor VIII based on the rationale that it is less susceptible to inactivation by circulating human factor VIII antibodies.
''The approval of OBIZUR is welcome news for the hemophilia community based on the data from the first clinical trial designed specifically for acquired hemophilia A, which found that all patients responded to treatment within 24 hours,'' said Dr. Rebecca Kruse-Jarres, Director of the Hemophilia Care Program at Puget Sound Blood Center in Seattle and the clinical trial’s principal investigator. ''Importantly, this new option to treat bleeding episodes will enable us to measure factor VIII levels, thus giving us an objective marker of hemostasis that can guide dosing and prevent overdosing.''
The approval is based on a global, prospective, controlled, multi-center Phase 2/3 open-label clinical trial that examined the efficacy of OBIZUR in the treatment of serious bleeding episodes in adults with AHA (29 patients evaluated for safety, 28 evaluated for efficacy). All patients treated with OBIZUR (28/28) showed a positive response, meaning an effective or partially effective response with bleeding stopped or reduced and clinical improvement, at 24 hours after the initial infusion. A total of 86 percent (24/28) had successful treatment of the initial bleeding episode. The overall treatment success was determined by the investigator based on the ability to discontinue or reduce the dose and/or dosing frequency of OBIZUR. Common adverse reactions observed in greater than five percent of 29 patients in the clinical trial were development of inhibitors to porcine FVIII.
''As a new treatment option with the ability to measure FVIII activity in the body, OBIZUR will address important unmet needs for patients with acquired hemophilia A, a potentially life-threatening condition,'' said Brian Goff, head of Baxter’s hemophilia franchise. ''This approval reflects Baxter’s long-standing commitment to discovering new options for hemophilia patients and adds to our portfolio of treatments that reduce the burden of these diseases.''
OBIZUR will be commercially available in the United States in the coming months and is currently under regulatory review in Europe and Canada.
About OBIZUR
OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence] is indicated for the treatment of bleeding episodes in adults with acquired hemophilia A.
Limitations of Use:
* Safety and Efficacy of OBIZUR has not been established in patients with baseline anti-porcine factor VIII inhibitor titer greater than 20 BU.
* OBIZUR is not indicated for the treatment of congenital hemophilia A or von Willebrand disease.
Detailed Important Risk Information for OBIZUR
CONTRAINDICATIONS
OBIZUR is contraindicated in patients who have had life-threatening hypersensitivity reactions to OBIZUR or its components (including traces of hamster proteins).
WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions can occur with OBIZUR. OBIZUR contains trace amounts of hamster proteins. Early signs of allergic reactions, which can progress to anaphylaxis, include angioedema, chest-tightness, dyspnea, hypotension, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if allergic or anaphylactic-type reactions occur.
Inhibitory Antibodies
Inhibitory antibodies to OBIZUR have occurred. Monitor patients for the development of antibodies to OBIZUR by appropriate assays. If the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled after OBIZUR administration, suspect the presence of an anti-porcine factor VIII antibody. If such inhibitory antibodies to anti-porcine factor VIII are suspected and there is a lack of clinical response, consider other therapeutic options.
Monitoring Laboratory Tests
* Perform one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and maintained
* Monitor factor VIII activity 30 minutes and 3 hours after initial dose
* Monitor factor VIII activity 30 minutes after subsequent doses
* Monitor the development of inhibitory antibodies to OBIZUR. Perform a Nijmegen Bethesda inhibitor assay if expected plasma factor VIII activity levels are not attained or if bleeding is not controlled with the expected dose of OBIZUR. Use Bethesda Units (BU) to report inhibitor levels.
ADVERSE REACTIONS
Common adverse reactions observed in greater than 5% of subjects in the clinical trial were development of inhibitors to porcine factor VIII.
Please see full prescribing information for OBIZUR at: www.baxter.com/downloads/healthcare_professionals/products/OBIZUR_PI.pdf.
About Acquired Hemophilia A
Acquired hemophilia A is a rare, potentially life-threatening bleeding disorder, which, unlike congenital hemophilia, typically affects older adults and occurs in both males and females. In acquired hemophilia A, individuals typically experience subcutaneous, soft tissue, and post-surgical bleeding. The comorbidities in this typically elderly population also pose a particular challenge to treat serious bleeding episodes.
About Baxter in Hemophilia
Baxter has more than 60 years experience in hemophilia and has introduced a number of therapeutic firsts for hemophilia patients. Baxter has the broadest portfolio of hemophilia treatments in the industry and is able to meet individual therapy choices, providing a range of options at each treatment stage. The company's work is focused on optimizing hemophilia care and improving the lives of people living with hemophilia A and B, as well as acquired hemophilia A, worldwide.
About Baxter International Inc.
Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.
This release includes forward-looking statements concerning OBIZUR, including expectations with regard to its potential impact on patients, commercial launch plans in the US and planned regulatory filings outside the US. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; product quality or supply or patient safety issues; changes in law and regulations; and other risks identified in Baxter's most recent filing on Form 10-K and other SEC filings, all of which are available on Baxter's website. Baxter does not undertake to update its forward-looking statements.

Obizur (Antihemophilic Factor [Recombinant], Porcine Sequence)
Generic Name: susoctocog alfa  
Trade Name: Obizur 
Synonym: OBI 1, recombinant porcine factor VIII 
Entry Type: New molecular entity  
Developmental Status
UK: Pre-registration (Filed) 
EU: Pre-registration (Filed) 
US: Pre-registration (Filed) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Jul 14: Filed in the EU via the centralised procedure [9].
17/09/2014 12:13:29 
Dec 13: Filed in the US for treatment of patients with acquired haemophilia A [8].
11/12/2013 21:56:11 
Nov 12: FDA assigns fast track status to OBI-1 in acquired haemophilia A [5].
22/11/2012 09:26:15 
Nov 10: PIII study started [2].
23/11/2010 09:27:24 
Granted Orphan drug status in the US (2004) and the EU (2010) [1]
23/11/2010 09:27:06 
Trial or other data
Dec 13: Results reported from the global, PII/III open label trial in 18 adults with acquired hemophilia A who presented with a serious bleed and were treated with an initial dose of OBI-1 (200 units/kg), followed by additional doses based on clinical evaluation and target factor VIII activity levels. The primary efficacy endpoint was defined by clinical assessment as effective or partially effective control of bleeding and FVIII activity levels at 24 hours after initiation of OBI-1 therapy. All patients in the study responded positively (14 effective / 4 partially effective) in the first 24 hours. No treatment-related serious adverse events were reported; non-serious mild AEs were reported in two patients (11.1%) who developed anti-porcine inhibitors to OBI-1 [8]
11/12/2013 22:01:03
Jan 13: Inspiration and Ipsen have agreed to sell OBI-1 (recombinant porcine FVIII) to Baxter International [6]. 
26/02/2013 10:27:31
July 12: Data from ongoing Phase 2/3 Accur8 Auto-antibody trial (n=15 to date). . The primary objective of the study is to evaluate the efficacy of OBI-1 treatment (200 units/kg on first injection, then dose based on target FVIII levels) for serious (life- or limb-threatening) bleeds in individuals age 18 and older with acquired haemophilia A, as measured by the control of bleeding 24 hrs after initial OBI-1 dose administration. Seven out of seven pts receiving OBI-1 experienced control of bleeds within 24 hrs and subsequent resolution of bleeds. Therapeutic FVIII activity levels were achieved and maintained with intermittent OBI-1 administration based on FVIII levels. [4]
10/07/2012 09:38:25
Nov 11: The second of two pivotal studies from OBI-1´s Accur8 clinical trial programme has started (NCT01434511). It will enrol 28 children ≥6 years of age with congenital hemophilia A, who have developed inhibitory antibodies to their human FVIII replacement therapy. OBI-1 will be given intravenously for 2-3 hourly during the first 24 hours of treatment. The study is being conducted in S. Africa and is due to complete Sep 14 [3]. 
29/11/2011 11:12:07
Nov 10: Inspiration Biopharmaceuticals has started the first of two PIII studies of OBI-1. It is a prospective, non-randomized, open-label study evaluating the efficacy of OBI-1 for the treatment of serious bleeding episodes in individuals with acquired hemophilia. Serious bleeding episodes include those that are a threat to a patient´s life or vital organs or limbs, or which require a blood transfusion. In addition, the study will obtain data about the pharmacokinetic behavior of OBI-1 [2].
23/11/2010 09:40:40
Jan 10: Inspiration Biopharmaceuticals has in-licensed OBI-1 from Ipsen will be responsible for the clinical development, regulatory process and commercialization of the product [2]. 
23/11/2010 09:40:19
Approximately one-third of individuals with hemophilia A develop an immune reaction to human FVIII (hFVIII). Current therapies, specifically human factor VIIa (NovoSeven®) and FEIBA, work by bypassing the natural hemostatic pathway and forcing coagulation with much higher levels of FVIIa than normal. OBI-1 is a recombinant form of porcine FVIII that possesses low cross reactivity to anti-hFVIII antibodies. OBI-1 should allow clinicians to correlate activity and efficacy with a biomarker and guide dosing to better predict treatment outcomes [2]. 
23/11/2010 09:40:08
References  
Available only to registered users
 Category
BNF Category: Drugs used in hypoplastic, haemolytic, and renal anaemias (09.01.03)
Pharmacology: recombinant porcine factor VIII (FVIII)  
Epidemiology: Acquired hemophilia, an autoimmune disease, is rare and is typically a disorder of older adults, both males and females. In acquired hemophilia, individuals typically bleed into the skin, muscles and soft tissues [2]. There were 5,424 patients with haemophilia A in the UK in 2011 (prevalence 8.7 per 100,000 population) [7]  
Indication: Haemophilia A 
Additional Details:  
Method(s) of Administration  
Intravenous infusion 
Company Information
Name: Baxter 
US Name: Baxter 
NICE Information
In timetable: -