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昨天，欧洲药监局已批准GSK/ Genmab出品的Arzerra上市销售，该药用于治疗难治型慢性淋巴细胞性白血病（CLL）。
去年10月份，Arzerra也已通过了FDA的批准，此次再度获准在欧洲市场上市，但产品的销售有一定的前提条件，即适用患者范围有限，只能用于那些采用标准药物（Genzyme公司Campath）或化学疗法药氟达拉宾（fludarabine）治疗之后无应答的CLL患者，他们只占这类患者总人数的25%左右。
有条件销售批准主要针对那些疗效显著，但同时用药风险也相对较高的产品。通常这种药物能够满足特定患者的需求，但还没有足够的数据证实它给患者带来的益处大于潜在的风险，从而还无法获得完全批准。根据相应要求，GSK在产品销售之后仍需向欧洲药监局递交补充数据。
Arzerra属于单克隆抗体类药物，它可以激活人体的免疫系统对抗正常或癌变的B细胞，同时它还可以附着于CD20分子（位于B细胞表面）抗原决定基。
GSK指出，几乎所有的CLL患者都会复发，因此治疗起来相当困难。目前针对该病的治疗药屈指可数且疗效有限，而无法使用氟达拉宾和Campath治疗的患者预后非常差，平均存活期仅为8个月。
相关专家表示，因为CLL患者每次接受治疗之后都有可能复发，现有药物对某些患者起不了什么作用，如果要延长他们的生命就得另辟蹊径，寻找全新有效的产品，而Arzerra正好可以满足他们的需求。
美国批准Arzerra用于治疗慢性淋巴细胞白血病
慢性淋巴细胞白血病概述
慢性淋巴细胞白血病简称慢淋，是一种起病缓慢的淋巴细胞系中某些免疫功能不全的淋巴细胞恶性增生性疾病。本病在我国少见，仅占白血病的３．４％，在欧美白种人中较常见占２５－３０％。发病年龄大多在５０岁以上、３０岁以下者很少见。男性比女性多。
慢性淋巴细胞白血病的主要表现
本病的主要表现是全身淋巴结肿大，脾大，贫血及外周血中淋巴细胞异常增多。
本病的病程长短悬殊，主要死亡原因为感染，尤其是肺炎多见。其他死亡原因有全身衰竭，骨髓造血功能衰竭引起的严重贫血或出血。治疗上以手术和化疗为主，最近，美国研究人员发现了一种新药，可以用于治疗慢性淋巴细胞白血病，获得美国政府的批准。
治疗慢性淋巴细胞白血病的新药-Arzerra
美国FDA已经批准Arzerra，一种单克隆抗体，用于治疗慢性淋巴细胞白血病（CLL）。丹麦Genmab制药公司公布了其在研新药Arzerra在一项中期临床实验中获得的首批数据，该药主要用于从未接受过任何治疗的慢性淋巴细胞白血病（CLL）患者，由Genmab和GSK共同研发。
在上述实验中，受试者为61名CLL患者，他们采用Arzerra+Fludarabine（氟达拉宾+Cyclophosphamide（环磷酰胺）进行治疗。
实验结果发现，采用500毫克Arzerra治疗的患者病情完全缓解率为32%，而采用1000毫克剂量的患者病情完全缓解率达到50%。此外，500毫克剂量受试组用药后总体应答率为77%，1000毫克剂量受试组对药物的总体应答率为73%。
Genmab公司表示，在为期30天用药过程中未出现意料之外的安全性问题，该药最常见的副作用为嗜中性白血球减少（出现几率为48%），其他常见不良反应（出现几率为15%）还包括恶心呕吐、皮疹、发热、头痛和血小板减少。
两个不同剂量受试组用药后出现上述不良反应的概率相当。其中有一位患者在实验过程中死亡，经调查人员核查之后证实该患者的死亡与Arzerra没有关联。
Indication
ARZERRA (ofatumumab) is indicated for thetreatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.
The effectiveness of ARZERRA is based on the demonstration of durable objective responses. No data demonstrate an improvement in disease-related symptoms or increasedsurvivalwithARZERRA.
Important Safety Information
Infusion Reactions
ARZERRAcancauseseriousinfusionreactionsmanifesting as bronchospasm, dyspnea, laryngealedema,pulmonary edema, flushing, hypertension, hypotension, syncope, cardiacischemia/infarction,backpain,abdominalpain,pyrexia,rash,urticaria,andangioedema.
Infusion reactions occur
more frequently with the first 2 infusions. Premedicate with acetaminophen, an antihistamine, and a corticosteroid. Interrupt infusion for infusion reactions of any severity.
Institute medical management for severe infusion reactions, including angina or other signs and symptoms of myocardial ischemia. In a study of patients with moderate to severe chronic obstructive pulmonary disease, an indication for which ARZERRA is not approved, 2 of 5 patients developed Grade 3 bronchospasm during infusion. Infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg), 29% on the day of the second infusion (2000 mg), and less frequently during subsequent infusions.
Cytopenias
Prolonged (≥1 week)severeneutropeniaandthrombocytopenia can occur with ARZERRA. Monitor complete blood counts (CBC) and platelet counts at regular intervals during therapy, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Of 108 patients with normal neutrophil counts at baseline, 45 (42%) developed ≥Grade 3neutropenia. Nineteen (18%) developed Grade 4 neutropenia. Some patients experienced new onset Grade 4 neutropenia >2 weeks in duration.
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur with ARZERRA. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms.
DiscontinueARZERRAifPMLissuspected,andinitiateevaluationforPML,includingconsultation with a neurologist, brain MRI, and lumbar puncture.
Hepatitis B Reactivation
Hepatitis B reactivation, including fulminant hepatitis and death, occurs with other monoclonal antibodies directed against CD20. Screen patients at high risk of hepatitis B virus (HBV) infection before initiation of ARZERRA. Closelymonitorcarriers of hepatitis B for clinical and laboratory signs of active HBV infection during treatment with ARZERRA and for 6 to 12 monthsfollowingthelastinfusionofARZERRA. Discontinue ARZERRA in patients who develop viralhepatitisorreactivation of viral hepatitis, and institute appropriate treatment. Insufficient data exist regarding the safety of administration of ARZERRA in patients with active hepatitis.
Intestinal Obstruction
Obstruction of the small intestine can occur in patients receiving ARZERRA. Perform a diagnostic evaluation if obstruction is suspected.
Immunizations
The safety of immunization with live viral vaccines during or followingadministration of ARZERRA has not been studied. Do not administer live viral vaccines to patients who have recently received ARZERRA.
The ability to generate an immune response to any vaccine followingadministration of ARZERRA has not been studied.
Most Common Adverse ReactionsIn the pivotal study (n=154) the most common adverse reactions (≥10%) were neutropenia, followed by pneumonia (23%), pyrexia (20%), cough (19%), diarrhea (18%), anemia (16%), fatigue (15%), dyspnea (14%), rash (14%), nausea (11%), bronchitis (11%), and upper respiratory tract infections (11%).
Most Common Serious Adverse Reactions In patients who received an infusion of 2000 mg of ARZERRA, the most common serious adverse reactions were infections (including pneumonia and sepsis), neutropenia, and pyrexia.
A total of 108 patients (70%)experiencedbacterial, viral, or fungal infections. A total of 45patients (29%) experienced ≥Grade 3 infections, of which 19 (12%) were fatal.
The proportion of fatalinfectionsinthefludarabine- and alemtuzumab-refractory group was 17%. |
