On October 26, 2012, the U. S. Food and Drug Administration granted accelerated approval to omacetaxine mepesuccinate, (SYNRIBO for Injection, for subcutaneous use, Teva Pharmaceutical Industries Ltd.), for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs).
The accelerated approval was based on combined data from two open label single-arm trials enrolling patients with CML in chronic phase (CML-CP) or in accelerated phase (CML-AP). The efficacy population included 76 patients with CML-CP and 35 patients with CML-AP who had received two or more prior TKIs, including imatinib. Major cytogenetic response (MCyR) and Major Hematologic Response (MaHR) were the primary endpoints for CML-CP and CML-AP, respectively. MCyR was achieved in 18.4% of patients with CML-CP (median response duration 12.5 months). MaHR was achieved in 14.3% of patients with CML-AP (median response duration 4.7 months).
Safety data were evaluated in 163 patients comprised of 108 patients with CML-CP and 55 patients with CML-AP who received at least one dose of omacetaxine mepesuccinate and an additional 4 patients with CML-CP from another open label, single arm trial. The most common (≥20%) grade 1-4 adverse reactions in the combined safety population of patients with CML-CP and AP included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection and lymphopenia. The most common (≥5%) grade 3-4 adverse reactions were thrombocytopenia, anemia, neutropenia, febrile neutropenia, asthenia/fatigue, pyrexia and diarrhea.
The most common serious adverse events (reported in ≥ 3 patients) were thrombocytopenia, anemia, neutropenia, febrile neutropenia, pyrexia, diarrhea, pneumonia, cerebral hemorrhage, gastrointestinal hemorrhage and sepsis. Ten deaths were reported within 30 days of the last omacetaxine mepesuccinate dose. Four of these were attributed to progressive disease, four to cerebral hemorrhage, one to multi-organ failure and one to unknown causes.
The recommended dose and schedule for omacetaxine mepesuccinate is1.25 mg/m2 subcutaneous injection twice daily for 14 days of a 28 day cycle for the induction phase and 1.25mg/m2 subcutaneous injection twice daily for 7 days of a 28 day cycle for maintenance.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm
, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).