——接受监管局批准的第一个抗-CD19药物
2014年12月3日，美国食品和药品监管局(FDA)批准Blincyto(blinatumomab)治疗有费城染色体费城前体B-细胞急性淋巴膜细胞白血病(B-细胞ALL)患者，一种非常见形式的ALL。
前体 B-细胞ALL是一种迅速升长类型癌症其中骨髓制造太多B-细胞原始淋巴细胞，一种不成熟的白细胞。白血病患者的骨髓细胞有时发生费城染色体[Philadelphia chromosome]是一种异常 。美国国家癌症研究所估计2014年6,020美国人将被诊断有ALL和1,440 将死于该病。
Blincyto是免疫治疗的实例，一种治疗用人免疫系统的某些部分与疾病斗争例如癌症。Blincyto是吸引机体T-细胞，白细胞或淋巴细胞的一种类型，破坏白血病细胞的第一个被批准药物。该药物作用如同一种蛋白被称为CD19，它在大多数B-细胞原始淋巴细胞表面发现，和CD3，在T-细胞淋巴细胞上一种蛋白间的一种连接剂[connector]。它意向治疗癌症治疗后返回(复发的)或对既往治疗 不反应(难治性)的患者。
FDA的药品评价和研究中心血液学和肿瘤学产品室主任Richard Pazdur，医学博士说：“免疫治疗，尤其是Blincyto有其独特的作用机制，对有白血病患者尤其鼓舞人有前途。“”“认识到这个新治疗的潜能，FDA与承办单位在我们突破性治疗指定程序下主动共事便于批准这个新型药物。”
FDA授权Blincyto突破性治疗指定，优先审评和孤儿产品指定因为承办单位通过初步临床证据分别显示该药可能提供一个实质上改善超过可得到的治疗；在申请递交时药物有潜力，将在一个严重情况治疗中显著改善安全性或有效性；和该药是意向治疗一种罕见病。Blincyto正在被批准提前5个月处方药物用户费用目标日期2015年5月19日，监管局计划完成申请评审的日期。
在涉及 185 例有费城染色体-阴性复发或难治性前体B-细胞ALL成年临床试验中评价的Blincyto安全性和有效性。所有参加者通过用Blincyto输注至少4周治疗，一种利用针注射治疗药至血流的方法。结果显示32%参加者无疾病证据(完全消退)共约6.7个月。
正在FDA的加速批准程序下批准Blincyto，该程序允许根据显示对一个替代性终点合理地可能预测对患者获益的临床数据批准一个药物治疗一种严重或危及生命疾病。当公司进行验证性临床试验这个程序提供患者较早得到鼓舞人有前途新药。FDA正在要求Blincyto的制造商进行一项研究证实药物在有复发的或难治性费城-阴性前体B-细胞ALL参加者中改进生存。
Blincyto带有一个黑框警告警戒患者和卫生保健专业人员有些临床试验参加者在首次治疗开始时有低血压和呼吸困难(细胞因子释放综合征)问题，经受一个短时间思想困难(脑病变encephalopathy)或在中枢神经系统中副作用。Blincyto-治疗参加者所见最常见副作用是发热，头痛，周边水肿，发热性中性粒细胞减少，恶心，低钾血症，疲乏，便秘，腹泻和震颤。
FDA批准Blincyto有一个风险评价和减轻战略(REMS)，由一个交流计划告知卫生保健提供者关于严重风险和为准备潜能和给药错误组成。
FDA Approves BLINCYTO™ (Blinatumomab) Immunotherapy for the Treatment of Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

BLINCYTO™
About BLINCYTO™ (blinatumomab)
BLINCYTO is the first BiTE® antibody construct and the first single-agent immunotherapy to be approved by the U.S. Food and Drug Administration (FDA).3 BLINCYTO was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the U.S. for the treatment of Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
About BiTE® Technology
Bispecific T cell engager (BiTE®) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE® antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE® antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.
Important U.S. Product Information
BLINCYTO is indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
•Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO™. Interrupt or discontinue BLINCYTO™ as recommended.
•Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO™. Interrupt or discontinue BLINCYTO™ as recommended.
Contraindications
BLINCYTO™ is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
•Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO™. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO™ as outlined in the Prescribing Information (PI).
•Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO™ in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO™ as outlined in the PI.
•Infections: Approximately 25% of patients receiving BLINCYTO™ experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO™ as needed.
•Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO™ treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO™ as needed to manage these events.
•Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO™ infusion and interrupt BLINCYTO™ if prolonged neutropenia occurs.
•Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO™ are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO™ is being administered.
•Elevated Liver Enzymes: Transient elevations in liver enzymes are associated with BLINCYTO™ treatment. The majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO™ treatment. BLINCYTO™ treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
•Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO™, especially in patients previously treated with cranial irradiation and anti-leukemic chemotherapy.
•Preparation and administration errors have occurred. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Adverse Events
•The most commonly reported adverse reactions (= 20%) in clinical trials were pyrexia (62%), headache (36%), peripheral edema (26%), febrile neutropenia (26%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%) and constipation (20%).
Dosage and Administration Guidelines
•BLINCYTO™ is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
•It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.