title: U.S. Food and Drug Administration approval summary: omacetaxine mepesuccinate as treatment for chronic myeloid leukemia.
abstract: 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.
authors: 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.
authors: Firoozeh
authors: F
authors: Alvandi
authors: Virginia E
authors: VE
authors: Kwitkowski
authors: Chia-Wen
authors: CW
authors: Ko
authors: Mark D
authors: MD
authors: Rothmann
authors: Stacey
authors: S
authors: Ricci
authors: Haleh
authors: H
authors: Saber
authors: Debasis
authors: D
authors: Ghosh
authors: Janice
authors: J
authors: Brown
authors: Erika
authors: E
authors: Pfeiler
authors: Elsbeth
authors: E
authors: Chikhale
authors: Joseph
authors: J
authors: Grillo
authors: Julie
authors: J
authors: Bullock
authors: Robert
authors: R
authors: Kane
authors: Edvardas
authors: E
authors: Kaminskas
authors: Ann T
authors: AT
authors: Farrell
authors: Richard
authors: R
authors: Pazdur
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017277:Drug Approval; D005260:Female; D006248:Harringtonines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D020533:Angiogenesis Inhibitors; D006248:Harringtonines; D000077863:Homoharringtonine
keywords: CML; Chronic myeloid leukemia; FDA; Omacetaxine mepesuccinate