FDA批准在美国引入首个基因疗法

FDA approvalbrings first gene therapy to the United States

FDA批准在美国引入首个基因疗法

CART-cell therapy approved to treat certain children and young adults with B-cellacute lymphoblastic leukemia

CAR T-cell疗法被批准用以治疗某些儿童或者青少年急性B淋巴细胞白血病。

August 30,2017

2017年8月30日

Release

发布

Thisrelease was updated on Aug. 30, 2017 to correctly identify the FDA designati**granted to Kymriah.

该版本于2017年8月30日更新，以正确识别FDA授予于的名称Kymriah。

The U.S. Foodand Drug Administration issued a historic action today making the first genetherapy available in the United States, ushering in a new approach to thetreatment of cancer and other serious and life-threatening diseases.

FDA今天发布了一项历史性行动即首次在美国使用基因疗法，传达一个新的治疗癌症和其他威胁生命疾病的方法。

The FDAapproved Kymriah (tisagenlecleucel) for certain pediatric and young adultpatients with a form of acute lymphoblastic leukemia (ALL).

FDA批准Kymriah(tisagenlecleucel)用于治疗患有急性淋巴细胞白血病的儿童和青少年。

“We’reentering a new frontier in medical innovation with the ability to reprogram apatient’s own cells to attack a deadly cancer,” said FDA Commissioner ScottGottlieb, M.D. “New technologies such as gene and cell therapies hold out thepotential to transform medicine and create an inflection point in our abilityto treat and even cure many intractable illnesses. At the FDA, we’re committedto helping expedite the development and review of groundbreaking treatmentsthat have the potential to be life-saving.”

“在医疗方面的改革，我们正在步入一个新的阶段，我们可以重新规划病人自己的细胞来攻击致命的癌症。”FDA局长斯科特.戈特利布说。“基因和细胞疗法等新技术有望改变医学的发展潜力，在我们治疗甚至治愈许多棘手疾病的能力上，创造一个转折点”

Kymriah, acell-based gene therapy, is approved in the United States for the treatment ofpatients up to 25 years of age with B-cell precursor ALL that is refractory orin second or later relapse.

Kymriah是一个细胞基因疗法，被美国批准用以治疗25岁以下患有难治的或在二次或以后复发B-细胞前体急性淋巴细胞白血病的病人。

Kymriah is agenetically-modified autologous T-cell immunotherapy. Each dose of Kymriah is acustomized treatment created using an individual patient’s own T-cells, a typeof white blood cell known as a lymphocyte. The patient’s T-cells are collectedand sent to a manufacturing center where they are genetically modified toinclude a new gene that contains a specific protein (a chimeric antigenreceptor or CAR) that directs the T-cells to target and kill leukemia cellsthat have a specific antigen (CD19) on the surface. Once the cells aremodified, they are infused back into the patient to kill the cancer cells.

Kymriah是一种基因改良的自体T细胞免疫疗法。Kymriah的每一剂量都是通过改造病人自身的T细胞的一次定制治疗。将患者的T细胞经过挑选后传递至生产中心，在这里这些细胞将会被转基因，被改造成含有特定蛋白质的新基因（嵌合抗原受体或CAR），从而直接指导T细胞靶向定位和杀死表面含有特殊抗原（CD19）的病变细胞。一旦细胞被修改，它们就会被注入到病患体内用来杀死癌症细胞。

ALL is acancer of the bone marrow and blood, in which the body makes abnormallymphocytes. The disease progresses quickly and is the most common childhoodcancer in the U.S. The National Cancer Institute estimates that approximately3,100 patients aged 20 and younger are diagnosed with ALL each year. ALL can beof either T- or B-cell origin, with B-cell the most common. Kymriah is approvedfor use in pediatric and young adult patients with B-cell ALL and is intendedfor patients whose cancer has not responded to or has returned after initialtreatment, which occurs in an estimated 15-20 percent of patients.

急性淋巴细胞白血病是骨髓及血液的癌症，身体会在骨髓和血液中产生异常的淋巴细胞。这种疾病发展比较迅速，在美国儿童癌症中最为普遍。国家癌症机构评估结果显示每年大约3100位20岁以下年轻病患被诊断患有急性淋巴细胞白血病。急性淋巴细胞白血病源于T-或B-细胞，B-细胞更普遍一些。Kymriah被批准用于治疗儿童和青少年B-细胞急性淋巴细胞白血病，被试图用于临床治疗后没有反应或转变的癌症患者，经过评估会出现在15-20%的病人身上。

“Kymriahis a first-of-its-kind treatment approach that fills an important unmet needfor children and young adults with this serious disease,” said Peter Marks,M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research(CBER). “Not only does Kymriah provide these patients with a new treatmentoption where very limited opti** existed, but a treatment option that hasshown promising remission and survival rates in clinical trials.”

“对有严重疾病儿童和青少年来说，Kymriah是一种首开先河的治疗方法，填补了一个重要的空缺”FDA生物制品评估和研究中心主任peter博士说。“Kymriah不仅为这些患者提供了一种新的治疗方案，这种治疗方案的选择非常有限，而且在临床试验中显示出有希望的缓解和生存率。”

The safety andefficacy of Kymriah were dem**trated in one multicenter clinical trial of 63pediatric and young adult patients with relapsed or refractory B-cell precursorALL. The overall remission rate within three months of treatment was 83percent.

Kymriah的安全性和有效性在一个多中心的临床试验中得到证实，63名儿科和年轻的成年患者的复发或难治的B-细胞前体急性淋巴细胞白血病。在治疗三个月内的整体缓解率为83%。

Treatment withKymriah has the potential to cause severe side effects. It carries a boxedwarning for cytokine release syndrome (CRS), which is a systemic resp**e tothe activation and proliferation of CAR T-cells causing high fever and flu-likesymptoms, and for neurological events. Both CRS and neurological events can belife-threatening. Other severe side effects of Kymriah include seriousinfecti**, low blood pressure (hypotension), acute kidney injury, fever, anddecreased oxygen (hypoxia). Most symptoms appear within one to 22 daysfollowing infusion of Kymriah. Since the CD19 antigen is also present on normalB-cells, and Kymriah will also destroy those normal B cells that produceantibodies, there may be an increased risk of infecti** for a prolonged periodof time.

Kymriah的治疗有可能引起严重的副作用。它对细胞因子释放综合症（CRS）有一个方框警告，对CAR-T细胞的激活和增殖的系统反应会导致高烧和流感样症状，以及神经系统疾病。细胞因子释放综合症和神经系统疾病是危及生命的。Kymriah的其他副反应包括严重感染、低血压、急性肾损伤、发烧和缺氧。大多数的症状会出现在服用Kymriah的1到20天内。因为CD19抗原也会出现在正常的B-细胞上，Kymriah也会破坏这些产生抗体的正常B细胞，在很长一段时间内，感染的风险可能会增加。

The FDA todayalso expanded the approval of Actemra (tocilizumab) to treat CAR T-cell-inducedsevere or life-threatening CRS in patients 2 years of age or older. In clinicaltrials in patients treated with CAR-T cells, 69 percent of patients hadcomplete resolution of CRS within two weeks following one or two doses ofActemra.

今天FDA扩大了托珠单抗的批准范围，治疗两岁或两岁以上患有CART细胞诱发的严重的或威胁生命的CRS的病人。CAR-T细胞治疗临床试验中，病人在两周内服用1或2个剂量Actemra，有69%的病人对CRS是完全吸收的。

Because of therisk of CRS and neurological events, Kymriah is being approved with a riskevaluation and mitigation strategy (REMS), which includes elements to assuresafe use (ETASU). The FDA is requiring that hospitals and their associatedclinics that dispense Kymriah be specially certified. As part of thatcertification, staff involved in the prescribing, dispensing, or administeringof Kymriah are required to be trained to recognize and manage CRS andneurological events. Additionally, the certified health care settings arerequired to have protocols in place to ensure that Kymriah is only given topatients after verifying that tocilizumab is available for immediate administration.The REMS program specifies that patients be informed of the signs and symptomsof CRS and neurological toxicities following infusion – and of the importanceof promptly returning to the treatment site if they develop fever or otheradverse reacti** after receiving treatment with Kymriah.

由于CRS和神经系统疾病的风险，Kymriah正在接受风险评估和缓解策略（REMS）的批准，其中包括确认安全使用（ETASU）的要素。FDA证要求医院及其相关诊所豁免Kymriah特别认证。作为认证的一部分，需要对Kymriah的处方、分发和管理工作人员进行培训以识别和管理CRS和神经系统疾病。此外，经认证的卫生保健机构必须有适当的协议，以确保Kymriah仅供患者使用，以确保其可立即进行治疗。REMS项目规定，患者需要被告知接受注射后的CRS症状和表现以及神经系统毒性，以及如果他们在接受治疗后出现发烧或其他不良反应，迅速返回治疗地点的重要性。

To furtherevaluate the long-term safety, Novartis is also required to conduct apost-marketing observational study involving patients treated with Kymriah.

为了进一步评估长期安全性，诺华还需要进行一项涉及Kymriah治疗患者的上市后观察性研究。

The FDAgranted Kymriah Priority Review and Breakthrough Therapy designati**. TheKymriah application was reviewed using a coordinated, cross-agency approach.The clinical review was coordinated by the FDA's Oncology Center of Excellence,while CBER conducted all other aspects of review and made the final productapproval determination.

FDA允许Kymriah优先审评并突破治疗命名法。Kymriah申请采用一个协调交叉的方法进行审评。临床试验审评是由FDA的肿瘤学卓越中心协调，CBER实施所有其他方面的审评并作出最后的制剂批准决策。

The FDAgranted approval of Kymriah to Novartis Pharmaceuticals Corp. The FDA grantedthe expanded approval of Actemra to Genentech Inc.

FDA批准了诺华制药公司的Kymriah。FDA扩大批准了的泰克公司的托珠单抗。

The FDA, anagency within the U.S. Department of Health and Human Services, protects thepublic health by assuring the safety, effectiveness, and security of human andveterinary drugs, vaccines, and other biological products for human use, andmedical devices. The agency also is resp**ible for the safety and security ofour nation’s food supply, cosmetics, dietary supplements, products that giveoff electronic radiation, and for regulating tobacco products.

FDA是美国卫生和公众服务部的一个机构，它通过确保人类和兽药、疫苗和其他生物制品的安全性、有效性和安全性来保护公众健康，并确保人类使用和医疗设备的安全。该机构还负责我们国家食品供应、化妆品、膳食补充剂、电子辐射产品以及烟草产品的安全与安全。

RelatedInformation

相关信息

• FDA:     Cellular and Gene Therapy Products
  
• FDA:     Oncology Center of Excellence
  
• NIH: Childhood Acute Lymphoblastic     Leukemia
  
• FDA:     What is Gene Therapy?
  
• FDA:     Kymriah (tisagenlecleucel) product page
  
• FDA:     Approved Cellular and Gene Therapy Products