【奥译言】一种急性骨髓性白血病新疗法获得FDA批准

2018-11-26 09:19 阅读数：3558 标签：

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美国食品药品监督管理局（FDA）于2018年11月21日批准了Daurismo （glasdegib）药片与低剂量阿糖胞苷（LDAC）化疗联用，用于治疗75岁以上或患有其他可能导致无法进行强化化疗的慢性健康问题或疾病的成人急性骨髓性白血病（AML）初诊患者。

“强化化疗通常用于控制急性骨髓性白血病，但是许多急性骨髓性白血病成年患者往往无法进行强化化疗，因其具有毒性。获批的Daurismo药品为医护人员提供了另外一种急性骨髓性白血病治疗方案，可以满足这些患者的不同需要。临床试验表明，Daurismo与LDAC组合疗法延长了患者的总生存期，而LDAC只适用于那些不能接受强化化疗的患者。”FDA肿瘤卓越中心主任兼FDA药品评估与研究中心（CDER）的血液学和肿瘤学产品办公室代理主任Richard Pazdur博士如是说。

急性骨髓性白血病是一种进展迅速的癌症，发生于骨髓中，会造成血液和骨髓中的白细胞异常增多。根据美国国立卫生研究院（NIH）所属的国家癌症研究所（NCI）估计，2018年将会有约19520人被诊断为急性骨髓性白血病患者，其中约10670名该病患者会因此去世。由于存在合并症和化疗相关毒性，几乎一半确诊患有急性骨髓性白血病的成年患者未接受强化化疗。

一项随机临床试验对Daurismo的疗效进行了研究，在该试验中，111名初诊急性骨髓性白血病成年患者接受了Daurismo与LDAC联合治疗或LDAC单药治疗。该试验对患者的总生存期（自随机接受治疗开始至因任何原因引起死亡的时间）进行了研究。结果显示，使用Daurismo治疗的患者的总生存期明显改善。接受Daurismo和LDAC组合疗法的患者的中位总生存期为8.3个月，而采用LDAC单药治疗的患者的中位总生存期为4.3个月。

临床试验中接受Daurismo治疗的患者出现的常见副作用包括：红细胞计数低（贫血）、疲劳（倦）、出血、伴随低白细胞计数的发热（发热性中性粒细胞减少症）、肌肉疼痛、恶心、手臂或腿部肿胀（水肿）、血小板计数低（血小板减少症）、呼吸短促（呼吸困难）、食欲下降、味觉不良（味觉障碍）、口腔或咽喉疼痛或溃疡（粘膜炎）、便秘和皮疹。

Daurismo的处方信息包含黑框警告，告知专业医护人员和患者该药品存在导致胎儿死亡或严重出生缺陷的风险。怀孕或哺乳期间不应进行Daurismo治疗。在开始Daurismo治疗前，育龄女性应进行妊娠检测，治疗期间和最后一次治疗后至少30天内应注意采取有效避孕措施。黑框警告内容还表明，男性患者通过精液接触药物存在潜在风险，并建议他们在治疗期间和最后一次治疗后至少30天内与怀孕伴侣或可能怀孕的女性伴侣一起使用避孕套。Daurismo必须随附一份患者用药指南，描述有关该药物使用和风险的重要信息。此外，建议患者在治疗期间不要献血或捐献血液制品。医护人员还应监测患者的心电活动变化，即QT间期延长。

美国FDA已授予Daurismo优先审查资格。同时，该药还获得FDA“孤儿药”资格认定，这是为帮助和鼓励罕见疾病药物研发所提供的奖励机制。

该机构已经批准辉瑞（Pfizer）公司开发的Daurismo（glasdegib）上市。

作为美国健康与人类服务部（DHHS）的一个下属分支机构，FDA致力于通过保证人用药和兽药、疫苗和其它人用生物制品、以及医疗器械的安全性和有效性来保护公共卫生。此外，FDA还负责美国食品供应、化妆品、保健品和放射性产品的安全，并对烟草制品进行监管。

英语原文

FDA approves new treatment forpatients with acute myeloid leukemia

The U.S. Food and Drug Administration today approved Daurismo(glasdegib) tablets to be used in combination with low-dose cytarabine (LDAC),a type of chemotherapy, for the treatment of newly-diagnosed acute myeloidleukemia (AML) in adults who are 75 years of age or older or who have otherchronic health conditions or diseases (comorbidities) that may preclude the useof intensive chemotherapy.

“Intensive chemotherapyis usually used to control AML, but many adults with AML are unable to haveintensive chemotherapy because of its toxicities. Today’s approval gives healthcare providers another tool to use in the treatment of AML patients withvarious, unique needs. Clinical trials showed that overall survival wasimproved using Daurismo in combination with LDAC compared to LDAC alone forpatients who would not tolerate intensive chemotherapy,” said Richard Pazdur,M.D., director of the FDA’s Oncology Center of Excellence and acting directorof the Office of Hematology and Oncology Products in the FDA’s Center for DrugEvaluation and Research.

AML is a rapidlyprogressing cancer that forms in the bone marrow and results in an increasednumber of abnormal white blood cells in the bloodstream and bone marrow. TheNational Cancer Institute at the National Institutes of Health estimates thatin 2018, approximately 19,520 people will be diagnosed with AML andapproximately 10,670 patients with AML will die of the disease. Almost half ofthe adults diagnosed with AML are not treated with intensive chemotherapybecause of comorbidities and chemotherapy related toxicities.

The efficacy of Daurismowas studied in a randomized clinical trial in which 111 adult patients withnewly diagnosed AML were treated with either Daurismo in combination with LDACor LDAC alone. The trial measured overall survival (OS) from the date ofrandomization to death from any cause. Results demonstrated a significantimprovement in OS in patients treated with Daurismo. The median OS was 8.3months for patients treated with Daurismo plus LDAC compared with 4.3 monthsfor patients treated with LDAC only.

Common side effectsreported by patients receiving Daurismo in clinical trials include low redblood cell count (anemia), tiredness (fatigue), bleeding (hemorrhage), feverwith low white blood cell count (febrile neutropenia), muscle pain, nausea,swelling of the arms or legs (edema), low platelet counts (thrombocytopenia),shortness of breath (dyspnea), decreased appetite, distorted taste (dysgeusia),pain or sores in the mouth or throat (mucositis), constipation and rash.

The prescribinginformation for Daurismo includes a Boxed Warning to advise health careprofessionals and patients about the risk of embryo-fetal death or severe birthdefects. Daurismo should not be used during pregnancy or while breastfeeding.Pregnancy testing should be conducted in females of reproductive age prior toinitiation of Daurismo treatment and effective contraception should be usedduring treatment and for at least 30 days after the last dose. The BoxedWarning also advises male patients of the potential risk of drug exposurethrough semen and to use condoms with a pregnant partner or a female partnerthat could become pregnant both during treatment and for at least 30 days afterthe last dose. Daurismo must be dispensed with a patient Medication Guide thatdescribes important information about the drug’s uses and risks. Patientsshould also be advised not to donate blood or blood products during treatment.Health care providers should also monitor patients for changes in theelectrical activity of the heart, called QT prolongation.

The FDA granted thisapplication Priority Review designation. Daurismo also received OrphanDrug designation, which provides incentives toassist and encourage the development of drugs for rare diseases.

The FDA granted theapproval of Daurismo to Pfizer.

The FDA, an agency withinthe U.S. Department of Health and Human Services, protects the public health byassuring the safety, effectiveness, and security of human and veterinary drugs,vaccines and other biological products for human use, and medical devices. Theagency also is responsible for the safety and security of our nation’s foodsupply, cosmetics, dietary supplements, products that give off electronicradiation, and for regulating tobacco products.

内容来自：FDA

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