What is the BLINCYTO™ REMS?

A Risk eva luation and Mitigation Strategy (REMS) is a program to manage known or potential serious risks associated with a drug product and is required by the Food and Drug Administration (FDA) to ensure that the benefits of the drug outweigh its risks.

The purpose of the BLINCYTO REMS is to inform Healthcare Providers about the following serious risks:

BOXED WARNING: Cytokine Release Syndrome

• Serious adverse events that may be associated with CRS included pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase, increased aspartate aminotransferase, and increased total bilirubin.
• The highest elevation of cytokines was observed in the first 2 days following start of BLINCYTO infusion.

BOXED WARNING: Neurological Toxicities

• In patients receiving BLINCYTO in clinical trials, neurological toxicities have occurred in approximately 50% of patients.
• The median time to onset of any neurological toxicity was 7 days.
• Grade 3 or higher (severe, life-threatening or fatal) neurological toxicities following initiation of BLINCYTO administration occurred in approximately 15% of patients and included encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The majority of events resolved following interruption of BLINCYTO, but some resulted in treatment discontinuation.

Preparation and Administration Errors

• Preparation and administration errors have occurred with BLINCYTO treatment.
• It is very important that the instructions for preparation (including admixing) and administration are strictly followed to minimize medication errors (including underdose and overdose).

BLINCYTO Fact Sheet:

A non-promotional REMS Fact Sheet reviewed by the FDA, with more detailed information on the serious risks associated with BLINCYTO is available in the “Materials for Healthcare Providers” section above.

INDICATION:

BLINCYTO is a bispecific CD19-directed CD3 T-cell engager indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). 

12月3日，美国FDA批准Blincyto (blinatumomab)用于治疗费城染色体阴性前体B细胞急性淋巴细胞白血病(B-cell ALL)患者，这种疾病是一种不常见形式的ALL。

前体B-cell ALL是一种增长快速的癌症，该病患者的骨髓产生太多的B细胞淋巴母细胞，这种细胞是一种不成熟的白细胞。费城染色体是有时发生在白血病患者骨髓中的一种异常。国家癌症研究所预测，2014年将有6020名美国人被确诊患有ALL，有1440人将死于这种疾病。

Blincyto是一种免疫治疗药物，这类药物可利用人体某部分免疫系统来抗击疾病如癌症。Blincyto是获批的首款通过人体T细胞来毁灭白血病细胞的药物，T细胞是一种白细胞或淋巴细胞。

这款药物可作为CD19蛋白与CD3蛋白之间的一种连接器，CD19被发现于大多数B细胞淋巴母细胞表面，而CD3是T细胞表面的一种蛋白质。这款药物适用于治疗后癌症又恶化（复发性）或对先前治疗无效（难治性）的患者。

“免疫治疗药物，尤其是拥有独特作用机制的Blincyto，对于白血病患者特别有前景，”FDA药物评价与研究中心代谢与肿瘤产品办公室主任、医学博士Pazdur称。“由于认识到了这种新型治疗药物的潜能，FDA在突破性治疗药物资格计划下积极与药物申请者一起努力促使这种新型药物获得批准。”

由于申请者通过初步临床前证据证明这款药物与现有可供使用治疗药物相比，可能会提供实质性疾病改善；这款药物在被提交上市申请时，对一种严重疾病治疗的安全性或有效性可能有明显改善；以及这款药物旨在治疗一种罕见疾病，所以FDA分别授予Blincyto突破性治疗药物资格、优先审评及孤儿药资格。

Blincyto的获批时间与其处方药申请者付费目标日期2015年5月19日相比提前了5个多月，处方药申请者付费目标日期是FDA计划完成药物审评的日期。

Blincyto的安全性及有效性在一项有185名费城染色体阴性复发或难治性前体B-cell ALL患者参与的临床研究中得到评价。所有患者均以Blincyto输液（一种通常利用针头将药物注射入血流中的方式）治疗至少4周。结果显示，32%的受试者大约在6.7个月的时间未出现疾病证据（完全缓解）。

Blincyto是在FDA加速批准计划下得到批准的，这一计划允许FDA基于显示一款药物对一种合理可能预测患者临床收益的代理终点有效的临床数据来批准该药物治疗一种危及生命的疾病。

这一计划可以更早地让患者获取有前景的新药，但申请该药物的公司需要进行确证性临床试验。FDA要求Blincyto生产商进行一项研究，以证实这款药物可以改善复发或难治性费城染色体阴性前体B-cell ALL受试者的生存期。

Blincyto带有一项黑框警告，提醒患者及卫生保健专业人员，一些临床试验受试者出现低血压及治疗初期呼吸困难问题，并经历短期思维困难（脑病）或其它神经系统副作用。

在Blincyto治疗患者中，最常见的副作用有发烧(发热)、头痛、组织肿胀(外围性水肿)、白细胞数量低引起发热(发热性中性粒细胞减少)、恶心、低钾(低钾血症)、疲劳、便秘、腹泻及震颤。

FDA批准Blincyto时带有一项风险评估及减灾策略(REMS)，它包含一项沟通计划，用以告知卫生保健供应商有关产品的严重风险及准备和管理差错的可能性。Blincyto由位于美国加利福尼亚州千橡市的安进上市销售
 

View the label approved on 12/03/2014 (PDF)¹¹ for BLINCYTO, BLA no. 125557