【重磅】FDA批准诺华的CD19-CART细胞药物上市，商品名为Kymriah丨医麦猛爆料

今天是2017年8月31日

农历七月初十

医麦客：细胞治疗的历史时刻【8-30】

2017年8月31日/医麦客 eMedClub/--美国FDA刚刚发布了历史性的重磅消息，第一个基因治疗方法CAR-T细胞药物批准上市。这样的治疗药物获批，让癌症和其他严重和危及生命的疾病有了新的合法的治疗选择。

FDA批准的第一个CAR-T药物

适应症：儿童和年轻成年患者急性淋巴细胞性白血病（ALL）

药品商品名：Kymriah（tisagenlecleucel）

Scott Gottlieb博士

FDA专员Scott Gottlieb博士说：“我们正在进入一个新的医疗创新新时代，通过重编病人自己的细胞来攻击致命的癌细胞，基因和细胞疗法等新技术有可能推动转化医学的发展，并在我们治疗和治愈许多难治性疾病的能力方面创造了一个新拐点。而伟大的FDA一直致力于帮助加快开发和审查有潜力挽救生命的突破性治疗药物。”

Kymriah，是一种基于细胞改造的基因治疗，在美国被批准用于治疗高达25岁的患有难治性或复发的急性淋巴细胞性白血病（ALL）的患者。

Kymriah是一种基因修饰的自体T细胞免疫治疗。每个剂量的Kymriah是使用个体患者自己的T细胞（称为淋巴细胞的一种白细胞）产生的定制化治疗。患者的T细胞被收集并送到制备中心，在那里进行遗传修饰（嵌合抗原受体或CAR的新基因表达），其指导T细胞靶向并杀死具有表面上的特异性抗原（CD19）。一旦细胞被修饰，在它们被注入到患者体内时可以杀死癌细胞。

ALL是骨髓和血液中的一种癌症，身体内的淋巴细胞异常。疾病进展很快，是美国最常见的儿童癌症。国家癌症研究所估计，每年约有3,100名年龄在20岁以下的患者被诊断为ALL。 ALL可以是T-细胞或B细胞来源，B细胞是最常见的。 Kymriah被批准用于患有B细胞ALL的儿科和年轻成人患者，适用于复发难治性ALL患者，这类患者所占比例有15-20％。

FDA的生物制剂评估中心总监Peter Marks博士说：“Kymriah是首例以细胞为载体的基因治疗方法，可满足儿童和年轻人对这种严重疾病的重要需求。这类患者存在非常有限的选择，而Kymriah的出现不仅为这些患者提供了一种新的治疗方案，更重要的是在临床试验中可以显示出有希望的缓解率和提高存活率的治疗方案。

Kymriah的安全性和有效性在一项针对复发性或难治性B细胞ALL的儿科和年轻成人患者的多中心临床试验中得到证实。治疗三个月内的总体缓解率为83％。

用Kymriah治疗有潜在的严重副作用。可能会产生例如细胞因子释放综合征（CRS）的风险警告，因为CRS的存在，会引起高热和流感样症状，因为CAR T细胞的快速增殖，也产生神经系统损伤的重度损伤反应。 CRS和神经系统事件都可能危及生命。

Kymriah的其他严重副作用还包括严重感染，低血压（低血压），急性肾损伤，发热和氧气减少（缺氧）。大多数症状出现在输入Kymriah后1至22天。由于CD19抗原也存在于正常的B细胞上，而Kymriah也会破坏产生抗体的正常B细胞，因此存在长时间感染的增加风险。

同时，FDA今天还扩大了Actemra（托西珠单抗）的批准，以治疗2岁以上患者因CAR-T细胞诱导的严重或危及生命的CRS副反应。在用CAR-T细胞治疗的患者的临床试验中，69％的患者CRS在一个或两个剂量的Actemra后两周内完全消除。

FDA官方原文：

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

The FDA approved Kymriah (tisagenlecleucel) for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).

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

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

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

ALL is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes. The disease progresses quickly and is the most common childhood cancer in the U.S. The National Cancer Institute estimates that approximately 3,100 patients aged 20 and younger are diagnosed with ALL each year. ALL can be of either T- or B-cell origin, with B-cell the most common. Kymriah is approved for use in pediatric and young adult patients with B-cell ALL and is intended for patients whose cancer has not responded to or has returned after initial treatment, which occurs in an estimated 15-20 percent of patients.

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for 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 treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”

The safety and efficacy of Kymriah were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within three months of treatment was 83 percent.

Treatment with Kymriah has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. Both CRS and neurological events can be life-threatening. Other severe side effects of Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia). Most symptoms appear within one to 22 days following infusion of Kymriah. Since the CD19 antigen is also present on normal B-cells, and Kymriah will also destroy those normal B cells that produce antibodies, there may be an increased risk of infections for a prolonged period of time.

The FDA today also expanded the approval of Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older. In clinical trials in patients treated with CAR-T cells, 69 percent of patients had complete resolution of CRS within two weeks following one or two doses of Actemra.

Because of the risk of CRS and neurological events, Kymriah is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring that hospitals and their associated clinics that dispense Kymriah be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of Kymriah are required to be trained to recognize and manage CRS and neurological events. Additionally, the certified health care settings are required to have protocols in place to ensure that Kymriah is only given to patients after verifying that tocilizumab is available for immediate administration. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Kymriah.

To further evaluate the long-term safety, Novartis is also required to conduct a post-marketing observational study involving patients treated with Kymriah.

The FDA granted Kymriah Fast Track, Priority Review and Breakthrough Therapydesignations. The Kymriah 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 product approval determination.

The FDA granted approval of Kymriah to Novartis Pharmaceuticals Corp. The FDA granted the expanded approval of Actemra to Genentech Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

参考出处：

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm

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