【重磅】FDA批准諾華的CD19-CART細胞藥物上市，商品名為Kymriah丨醫麥猛爆料

今天是2017年8月31日

農曆七月初十

醫麥客：細胞治療的歷史時刻【8-30】

2017年8月31日/醫麥客 eMedClub/--美國FDA剛剛發布了歷史性的重磅消息，第一個基因治療方法CAR-T細胞藥物批准上市。這樣的治療藥物獲批，讓癌症和其他嚴重和危及生命的疾病有了新的合法的治療選擇。

FDA批准的第一個CAR-T藥物

適應症：兒童和年輕成年患者急性淋巴細胞性白血病（ALL）

藥品商品名：Kymriah（tisagenlecleucel）

Scott Gottlieb博士

FDA專員Scott Gottlieb博士說：「我們正在進入一個新的醫療創新新時代，通過重編病人自己的細胞來攻擊致命的癌細胞，基因和細胞療法等新技術有可能推動轉化醫學的發展，並在我們治療和治癒許多難治性疾病的能力方面創造了一個新拐點。而偉大的FDA一直致力於幫助加快開發和審查有潛力挽救生命的突破性治療藥物。」

Kymriah，是一種基於細胞改造的基因治療，在美國被批准用於治療高達25歲的患有難治性或複發的急性淋巴細胞性白血病（ALL）的患者。

Kymriah是一種基因修飾的自體T細胞免疫治療。每個劑量的Kymriah是使用個體患者自己的T細胞（稱為淋巴細胞的一種白細胞）產生的定製化治療。患者的T細胞被收集並送到製備中心，在那裡進行遺傳修飾（嵌合抗原受體或CAR的新基因表達），其指導T細胞靶向並殺死具有表面上的特異性抗原（CD19）。一旦細胞被修飾，在它們被注入到患者體內時可以殺死癌細胞。

ALL是骨髓和血液中的一種癌症，身體內的淋巴細胞異常。疾病進展很快，是美國最常見的兒童癌症。國家癌症研究所估計，每年約有3,100名年齡在20歲以下的患者被診斷為ALL。 ALL可以是T-細胞或B細胞來源，B細胞是最常見的。 Kymriah被批准用於患有B細胞ALL的兒科和年輕成人患者，適用於複發難治性ALL患者，這類患者所佔比例有15-20％。

FDA的生物製劑評估中心總監Peter Marks博士說：「Kymriah是首例以細胞為載體的基因治療方法，可滿足兒童和年輕人對這種嚴重疾病的重要需求。這類患者存在非常有限的選擇，而Kymriah的出現不僅為這些患者提供了一種新的治療方案，更重要的是在臨床試驗中可以顯示出有希望的緩解率和提高存活率的治療方案。

Kymriah的安全性和有效性在一項針對複發性或難治性B細胞ALL的兒科和年輕成人患者的多中心臨床試驗中得到證實。治療三個月內的總體緩解率為83％。

用Kymriah治療有潛在的嚴重副作用。可能會產生例如細胞因子釋放綜合征（CRS）的風險警告，因為CRS的存在，會引起高熱和流感樣癥狀，因為CAR T細胞的快速增殖，也產生神經系統損傷的重度損傷反應。 CRS和神經系統事件都可能危及生命。

Kymriah的其他嚴重副作用還包括嚴重感染，低血壓（低血壓），急性腎損傷，發熱和氧氣減少（缺氧）。大多數癥狀出現在輸入Kymriah后1至22天。由於CD19抗原也存在於正常的B細胞上，而Kymriah也會破壞產生抗體的正常B細胞，因此存在長時間感染的增加風險。

同時，FDA今天還擴大了Actemra（托西珠單抗）的批准，以治療2歲以上患者因CAR-T細胞誘導的嚴重或危及生命的CRS副反應。在用CAR-T細胞治療的患者的臨床試驗中，69％的患者CRS在一個或兩個劑量的Actemra后兩周內完全消除。

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.

參考出處：

為生物醫藥發聲的專業媒體人

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