10月19日，美国FDA宣布批准了Kite Pharma的CAR-T疗法Yescarta（axicabtagene ciloleucel）上市，治疗罹患特定类型的大B细胞淋巴瘤成人患者。这些患者曾接受了至少两次其他治疗，但没有出现缓解，或是疾病出现复发。值得一提的是，这是美国FDA批准的首款针对特定非霍奇金淋巴瘤的CAR-T疗法，也是第二款获批的CAR-T疗法。

弥漫性大B细胞淋巴瘤（DLBCL）是成人中最为常见的非霍奇金淋巴瘤。据估计，每年美国约有72000例新发霍奇金淋巴瘤，其中三分之一是DLBCL。Kite带来的这款CAR-T疗法有望对包括DLBCL在内的多款大B细胞淋巴瘤进行治疗，改善患者预后。

在一项多中心的临床试验中，超过100名成人患者接受了Yescarta的治疗，并展现了令人振奋的疗效——研究人员发现，Yescarta带来的完全缓解率（CR）可达到51%！基于它的出色疗效，美国FDA曾授予它孤儿药资格，突破性疗法认定，以及优先审评资格。今日，Yescarta为患者带来的治疗潜力也使美国FDA对其上市亮了绿灯。

▲现任美国FDA局长Scott Gottlieb博士（图片来源：NBC News）

“今日标志着这一全新疗法开发道路上的又一座里程碑。在短短的几十年里，基因疗法从充满潜力的概念，变成了可实际操作的方案，治疗难治而致命的癌症，”美国FDA局长Scott Gottlieb博士说道：“这一批准彰显了这一新药领域的持续动力。我们承诺将支持和加速这类产品的开发。不久后，我们将公布详细的政策，介绍我们将如何支持基于细胞的医药开发。这个政策也将解释我们会如何在突破性的CAR-T细胞疗法和其他基因疗法中应用我们的加速项目。我们将继续支持基于这些新科学平台的安全有效疗法的高效开发。”

“Yescarta的获批让CAR-T这一全新细胞疗法能用于额外的癌症患者，这些淋巴瘤患者对先前的治疗没有响应，几乎没有其他治疗方案。”美国FDA生物制品评估和研究（CBER）主任Peter Marks博士说道。

我们祝贺又一款CAR-T疗法能够上市，造福患者。也祝愿Juno、bluebird bio/Celgene的CAR-T疗法研发顺利，早日上市，拯救病患！

FDA原文大赏

The U.S. Food and Drug Administration today approved Yescarta (axicabtagene ciloleucel), a cell-based gene therapy, to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment. Yescarta, a chimeric antigen receptor (CAR) T cell therapy, is the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL).

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer,” said FDA Commissioner Scott Gottlieb, M.D. “This approval demonstrates the continued momentum of this promising new area of medicine and we’re committed to supporting and helping expedite the development of these products. We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine. That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies. We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms.”

Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in adults. NHLs are cancers that begin in certain cells of the immune system and can be either fast-growing (aggressive) or slow-growing. Approximately 72,000 new cases of NHL are diagnosed in the U.S. each year, and DLBCL represents approximately one in three newly diagnosed cases. Yescarta is approved for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including DLBCL, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma.

Each dose of Yescarta is a customized treatment created using a patient’s own immune system to help fight the lymphoma. The patient’s T-cells, a type of white blood cell, are collected and genetically modified to include a new gene that targets and kills the lymphoma cells. Once the cells are modified, they are infused back into the patient.

“The approval of Yescarta brings this innovative class of CAR-T cell therapies to an additional group of cancer patients with few other options – those adults with certain types of lymphoma that have not responded to previous treatments,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER).

The safety and efficacy of Yescarta were established in a multicenter clinical trial of more than 100 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Yescarta was 51 percent.

Treatment with Yescarta 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 neurologic toxicities. Both CRS and neurologic toxicities can be fatal or life-threatening. Other side effects include serious infections, low blood cell counts and a weakened immune system. Side effects from treatment with Yescarta usually appear within the first one to two weeks, but some side effects may occur later.

Because of the risk of CRS and neurologic toxicities, Yescarta 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 Yescarta be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Yescarta are required to be trained to recognize and manage CRS and nervous system toxicities. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop.

To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Yescarta.

The FDA granted Yescarta Priority Review and Breakthrough Therapydesignations. Yescarta also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The Yescarta application was reviewed using a coordinated, cross-agency approach. The clinical review was conducted 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 Yescarta to Kite Pharma, 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.

文章来源：药明康德/FDA