Office of Hematology and Oncology Products, Office of New Drugs, Office of Biostatistics, Office of Pharmaceutical Science, and Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2014 Jan;19(1):94-9. doi: 10.1634/theoncologist.2013-0077. Epub 2013 Dec 5.
On October 26, 2012, the U.S. Food and Drug Administration (FDA) granted accelerated approval to omacetaxine mepesuccinate (Synribo; Teva Pharmaceuticals USA, Inc., North Wales, PA, http://www.tevausa.com) for the treatment of adult patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). The approval was based on the FDA review of data from 111 patients with CML in CP or in AP who had received two or more prior TKIs, including imatinib. Major cytogenetic response was achieved in 18% of patients with CP, with a median response duration of 12.5 months. Major hematologic response was achieved in 14% of patients with AP, with a median response duration of 4.7 months. The FDA safety evaluation was based on submitted data from 163 patients with CP or AP CML who had received at least one dose of omacetaxine mepesuccinate. The safety evaluation was limited by the single-arm design of the clinical trials as conducted in a small number of previously treated patients. The most common (≥20%) adverse reactions of any grade in enrolled patients included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, and infection. The FDA concluded that omacetaxine mepesuccinate has shown activity and a favorable benefit-to-risk profile for the studied population of adult patients with CML (CP or AP) with resistance and/or intolerance to two or more TKIs. Further evidence of response durability to verify clinical benefit is pending.
2012 年 10 月 26 日，美国食品药品监督管理局（FDA）批准奥马环素甲磺酸盐（Synribo；Teva 制药美国公司，北威尔士，宾夕法尼亚州，http://www.tevausa.com）用于治疗对两种或两种以上酪氨酸激酶抑制剂（TKI）耐药和/或不耐受的慢性期（CP）或加速期（AP）慢性髓性白血病（CML）的成年患者。该批准基于 FDA 对 111 例 CP 或 AP 中接受两种或两种以上 TKI（包括伊马替尼）的 CML 患者数据的审查。CP 中 18%的患者获得主要细胞遗传学缓解，中位缓解持续时间为 12.5 个月。AP 中 14%的患者获得主要血液学缓解，中位缓解持续时间为 4.7 个月。FDA 的安全性评估基于至少接受过一次奥马环素甲磺酸盐治疗的 163 例 CP 或 AP CML 患者的提交数据。安全性评估受到临床试验单臂设计的限制，这些临床试验在少数先前治疗的患者中进行。纳入患者中任何级别最常见（≥20%）的不良反应包括血小板减少症、贫血、中性粒细胞减少症、腹泻、恶心、疲劳、乏力、注射部位反应、发热和感染。FDA 得出结论，奥马环素甲磺酸盐在对两种或两种以上 TKI 耐药和/或不耐受的 CP 或 AP CML 成年患者研究人群中显示出活性和有利的获益-风险特征。尚需进一步证明对耐药性的持久性应答以验证临床获益。
