U.S. Food and Drug Administration approval summary: omacetaxine mepesuccinate as treatment for chronic myeloid leukemia.

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 approvalwas basedontheFDAreviewofdata from111 patients withCML inCPor inAPwhohadreceivedtwoormorepriorTKIs, including imatinib. Major cytogenetic responsewas achieved in 18% ofpatientswithCP, withamedianresponsedurationof12.5 months. Major hematologic response was achieved in 14% of patients with AP, with a median response duration of 4.7 months. TheFDAsafetyevaluationwasbasedonsubmitteddata from 163 patients with CP or AP CML who had received at least one dose of omacetaxine mepesuccinate. The safety evaluationwas limited by the single-arm design of the clinical trials as conducted in a small number of previously treated patients. The mostcommon ($ 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.