首个凝血因子-白蛋白融合蛋白Idelvion (Factor IX, recombinant/albumin fusion protein)获美国FDA批准为B型血友病患者治疗新选择
近日，美国FDA批准CSL Behring的Idelvion，一种用于儿童和成人治疗B型血友病凝血因子IX(重组)融合白蛋白。Idelvion是第一个获得批准的凝血因子-白蛋白融合蛋白产品，也是第二个被批准的经过改性能在血液中更持久的凝血因子融合蛋白产品。
“Idelvion的批准为血友病B儿童及成年患者提供了另一种重要的治疗选择，可以帮助预防或控制出血，降低出血发作的频次，”FDA生物制剂评价与研究中心主任、医学博士、哲学博士Marks称。
据疾病控制与预防中心提供的信息，血友病B是一种罕见的遗传性血液疾病，它能够阻止血液正常凝结。这种疾病主要影响男性，很少影响女性。血友病B患者会经历反复的潜在严重出血发作，出血主要进入关节，这样关节可能会因出血而受损。
Idelvion被用于替代因子IX，因子IX是一种自然产生凝血因子，血友病B（也称先天性凝血因子IX缺乏或克雷司马斯病）患者这种凝血因子缺失（功能性缺陷）或有缺陷。Idelvion由重组体DNA技术将因子IX与白蛋白连接而成，白蛋白是血液中发现的一种蛋白，当静脉注射使用时，白蛋白可使该产品持续更久。
Idelvion旨在按需对出血发作进行控制与预防、对术后出血管理，并作为一种日常预防（预防法）措施降低出血发作的频次。以预防药物使用时，与未改进的因子IX相比，Idelvion潜在需要更少的注射频次。
批准日期：2016年3月4日；公司：CSL Behring
Idelvion（凝血因子IX[重组]，白蛋白融合蛋白；Coagulation Factor IX [Recombinant] Albumin Fusion Protein）冻干粉为溶液，静脉注射
最初美国批准：2016年
作用机理
IDELVION是重组蛋白质暂时替换丢失的凝血因子IX需要有效的止血。 IDELVION由遗传融合重组凝血因子IX和重组白蛋白。融合重组白蛋白延伸因子IX的半衰期[见说明和临床药理学]。
适应症和用途
Idelvion，适用在有血友病B儿童和成年(先天性因子IX缺乏)为：
⑴ 出血发作的按需控制和预防；
⑵ 出血的围手术处理；
⑶ 常规预防：为预防或减少出血发作的频数。
剂型和规格
Idelvion为冻干粉，每瓶规格为250，500，1000或2000 IU。
剂量和给药方法
⑴ 每小瓶Idelvion被标记有实际因子IX效力的国际单位(IU)。
⑵ 一个IU的Idelvion每kg体重预期增加因子IX循环活性如下：
① 青少年和成年：1.3IU/dL每IU/kg
② 儿童(<12岁)：1IU/dL每IU/kg
⑶ 静脉给予。输注速率不要超过10mL每分钟。
⑷ 用Idelvion剂量和时间依赖于因子IX缺乏的严重程度，出血部位和程度，和患者的临床情况，年龄和因子IX的恢复。
⑸ 用下列公式确定使用的初始剂量：
需要剂量(IU) = 体重(kg)×想要的因子IX升高(正常的%或IU/dL) ×((IU/kg每IU/dL)恢复的倒数)
⑹ 调整剂量根据患者的临床情况和反应。
⑺ 患者≥12岁：25-40IU/kg体重每7天。患者用该方案控制良好可转至一个14-天间隔在50-75IU/kg体重。
禁忌症
在对Idelvion或其组分，包括仓鼠蛋白质曽有危及生命超敏反应患者不要使用。
警告和注意事项
⑴ 可能超敏性反应，包括过敏反应。症状发生时应终止Idelvion和给予适当治疗。
⑵ 可能发生对Idelvion中和抗体(抑制剂)的发展。如患者血浆没有达到期望因子IX血浆恢复，或如用适当剂量出血没有被控制，进行一个分析测量因子IX抑制剂浓度。
⑶ 当使用含因子IX产品时发生血栓栓塞(如，肺栓塞，静脉血栓形成，和动脉血栓形成)。
⑷ 在有因子IX抑制剂和对因子IX过敏反应史血友病B患者用含因子IX-产品免疫耐受性诱导后曽报道肾病综合征。
⑸ 因子IX活性分析结果与所使用活化部分凝血酶时间的试剂的种类可能变化。
不良反应
在临床试验中报道的最常见不良反应(发生率 ≥1%)是头痛。
特殊人群使用
儿童：可能需要较高剂量或频繁给药。
包装规格/储存与处理
如何附送
IDELVION作为在含因子Ⅸ活性的标示量，在国际单位（IU）表示单次使用的小瓶冻干粉末提供的。
IDELVION包装用无菌水的2.5毫升（对于250，500或1000 IU小瓶重构）或5毫升（对于2000 IU小瓶重构）注射，USP，人们推出Mix2Vial滤波器输送装置，和一个无菌酒精棉签。部件不与天然橡胶胶乳制成。
储存和处理
在其包店IDELVION以避光。
在冰箱或室温2-25°C（36〜77°F）存放IDELVION包。不要冻结。
不要使用IDELVION或无菌水超出印在包装箱和瓶标签上的失效日期注入稀释剂。
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产地国家：美国
原产地英文商品名:
Idelvion Injection 250IU/vial
原产地英文药品名:
Coagulation Factor IX [Recombinant] Albumin Fusion Protein
中文参考商品译名:
Idelvion注射剂 250单位/瓶
中文参考药品译名:
凝血因子IX[重组]，白蛋白融合蛋白
生产厂家中文参考译名:
CSL Behring
生产厂家英文名:
CSL Behring
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产地国家：美国
原产地英文商品名:
Idelvion Injection 500IU/vial
原产地英文药品名:
Coagulation Factor IX [Recombinant] Albumin Fusion Protein
中文参考商品译名:
Idelvion注射剂 500单位/瓶
中文参考药品译名:
凝血因子IX[重组]，白蛋白融合蛋白
生产厂家中文参考译名:
CSL Behring
生产厂家英文名:
CSL Behring
------------------------------------------
产地国家：美国
原产地英文商品名:
Idelvion Injection 1000IU/vial
原产地英文药品名:
Coagulation Factor IX [Recombinant] Albumin Fusion Protein
中文参考商品译名:
Idelvion注射剂 1000单位/瓶
中文参考药品译名:
凝血因子IX[重组]，白蛋白融合蛋白
生产厂家中文参考译名:
CSL Behring
生产厂家英文名:
CSL Behring
------------------------------------------
产地国家：美国
原产地英文商品名:
Idelvion Injection 2000IU/vial
原产地英文药品名:
Coagulation Factor IX [Recombinant] Albumin Fusion Protein
中文参考商品译名:
Idelvion注射剂 2000单位/瓶
中文参考药品译名:
凝血因子IX[重组]，白蛋白融合蛋白
生产厂家中文参考译名:
CSL Behring
生产厂家英文名:
CSL Behring

U.S. FDA Approves CSL Behring’s IDELVION® -- The First and Only Hemophilia B Therapy with Up to 14-day Dosing Intervals
In clinical trials, IDELVION maintained factor IX activity levels above 5 percent over 14 days, resulting in a median annualized spontaneous bleeding rate (AsBR) of 0.00
IDELVION, CSL Behring’s long-acting recombinant albumin fusion protein, delivers on the company’s promise to develop and provide innovative specialty biotherapies that help people with serious medical conditions live full lives
CSL Behring announced today that the U.S. Food and Drug Administration (FDA) has approved IDELVION® [Coagulation Factor IX (Recombinant), Albumin Fusion Protein], its novel, long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin for the treatment of hemophilia B. IDELVION is the first and only factor IX therapy that delivers high-level protection with up to 14-day dosing in appropriate patients. This dosing interval has been achieved while maintaining high levels of factor activity, above 5 percent over 14 days at 75 IU/kg. This reduces the monthly number of units needed for prophylaxis therapy.
IDELVION is indicated in children and adults with hemophilia B for routine prophylaxis to prevent or reduce the frequency of bleeding episodes; on-demand control and prevention of bleeding episodes; and the perioperative management of bleeding (around the time of surgery). Appropriate patients 12 and older can go up to 14 days between infusions. IDELVION is expected to be available later this month.
Hemophilia B is a congenital bleeding disorder characterized by deficient or defective factor IX; nearly all affected patients are male. People with hemophilia B may experience prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs. According to U.S. Centers for Disease Control and Prevention, the condition affects approximately one in 25,000 male births.
“The approval of this long-acting recombinant factor IX therapy for hemophilia B is vital, as physicians need more options to help their patients effectively and safely manage their bleeding disorder,” said Elena Santagostino, M.D., Ph.D., Professor in the Medical School of Clinical and Experimental Hematology at the University of Milan/IRCCS Maggiore Hospital, and lead investigator of the PROLONG-9FP clinical development program. “As the only recombinant factor IX therapy offering up to 14-day dosing, IDELVION helps patients maintain factor IX activity levels over a long period of time. This provides them with greater freedom from frequent infusions which is an important attribute for patients who require a prophylactic regimen but don’t want treatment to disrupt their active lives.”
The approval of IDELVION is based on results from the PROLONG-9FP clinical development program. PROLONG-9FP includes Phase I through Phase III open-label, multicenter studies evaluating the safety and efficacy of IDELVION in children and adults (ages 1 to 61 years) with hemophilia B (factor IX levels ≤ 2%).
“IDELVION has the potential to significantly impact the treatment of hemophilia B as it maintains factor IX activity levels above 5 percent over a prolonged period of time. This provides excellent bleeding control,” said Dr. Andrew Cuthbertson, Chief Scientific Officer and R&D Director, CSL Limited. “IDELVION is the first product from our innovative recombinant factor development program to receive FDA approval. We are proud to add this new therapy to our growing portfolio of bleeding disorder products, and are particularly excited about the positive impact treatment with IDELVION can have on the well-being of patients with hemophilia B.”
About PROLONG-9FP
The data from PROLONG-9FP showed median annualized spontaneous bleeding rates (AsBR) of zero and factor IX activity levels above 5 percent in patients using IDELVION® prophylactically. According to the World Federation of Hemophilia, patients with factor IX activity levels above 5 percent (and below 50 percent) are considered to have mild hemophilia. This result was achieved for both 14-day dosing and 7-day dosing. The data for on-demand therapy showed that 94 percent of bleeds were controlled with one infusion, while 99 percent were controlled with one or two infusions. The most common adverse reaction in clinical trials was headache. Data from PROLONG-9FP were recently published in the American Society of Hematology’s publication Blood.
About IDELVION
CSL Behring engineered IDELVION® to extend the half-life of recombinant factor IX through fusion with recombinant albumin. CSL Behring selected recombinant albumin as its fusion partner for its coagulation factor proteins due to its long physiological half-life.
IDELVION® is approved in Canada. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recently recommended granting marketing authorization for IDELVION in the European Union. Regulatory agencies in Australia, Switzerland and Japan are also currently reviewing CSL Behring’s license applications for IDELVION.
For more information about IDELVION, including full prescribing information, please visit http://labeling.cslbehring.com/PI/US/Idelvion/EN/Idelvion-Prescribing-Information.pdf. For more information about CSL Behring's recombinant products in development to treat hemophilia, visit http://www.cslbehring.com/products/bleeding-disorders/novel-recombinant-hemophilia-treatments.
Important Safety Information
IDELVION®, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rFIX-FP), is indicated in children and adults with hemophilia B (congenital factor IX deficiency) for:
On-demand control and prevention of bleeding episodes
Perioperative management of bleeding
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes
IDELVION is not indicated for induction of immune tolerance in patients with hemophilia B.
IDELVION is contraindicated in patients who have had life-threatening hypersensitivity to the product or its components, including hamster proteins.
IDELVION is for intravenous use only. IDELVION can be self-administered or administered by a caregiver with training and approval from a healthcare provider or hemophilia treatment center. Higher dose per kilogram body weight or more frequent dosing may be needed for pediatric patients.
Hypersensitivity reactions, including anaphylaxis, are possible. Advise patients who self-administer to immediately report symptoms of hypersensitivity, including angioedema, chest tightness, hypotension, generalized urticaria, wheezing, and dyspnea. If symptoms occur, discontinue IDELVION and administer appropriate treatment.
Development of neutralizing antibodies (inhibitors) to IDELVION may occur. If expected factor IX activity plasma levels are not attained or bleeding is not controlled with appropriate dose, perform an assay to measure factor IX inhibitor concentration. Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.
Thromboembolism (e.g., pulmonary embolism, venous thrombosis, and arterial thrombosis) can occur when using factor IX-containing products. In addition, nephrotic syndrome has been reported following immune tolerance induction in hemophilia B patients with factor IX inhibitors and allergic reactions to factor IX.
The most common adverse reaction (incidence ≥1%) reported in clinical trials was headache.
For indications, dosing and other information, please refer to the prescribing information.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f74301bf-95e2-44ab-a8b6-98aa07b04683