The US Food and Drug Administration (FDA) has approved omacetaxine mepesuccinate subcutaneous injection (Synribo, Teva Pharmaceutical Industries) for the treatment of adult patients with chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors (TKIs). Approval for omacetaxine mepesuccinate was granted on October 26, 2012.
The FDA approval was based on the combined results of 2 open-label, single-arm trials that enrolled patients with CML in chronic phase or accelerated phase. Patients in the trials had received 2 or more prior TKIs, including imatinib. The end points for the studies were major cytogenetic response for chronic-phase CML and major hematologic response for accelerated-phase CML. For those with chronic-phase CML, major cytogenetic response was achieved in 18.4% of patients (median response duration of 12.5 months). For patients with accelerated-phase CML, 14.3% achieved major hematologic response (median response duration of 4.7 months).
Thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection-site reaction, pyrexia, infection, and lymphopenia were the most common (≥20%) grades 1 to 4 adverse drug reactions. Thrombocytopenia, anemia, neutropenia, febrile neutropenia, asthenia/fatigue, pyrexia, and diarrhea were the most common (≥5%) grades 3 to 4 adverse drug reactions. Among the patients in the trials, 10 died within 30 days of the last omacetaxine mepesuccinate dose: 4 deaths were attributed to progressive disease, 4 to cerebral hemorrhage, 1 to multiorgan failure, and 1 to unknown causes.
Omacetaxine mepesuccinate was reviewed under the FDA’s accelerated approval review program that provides an expedited 6-month review for drugs that offer major
advances in treatment or that provide treatment when no adequate therapy exists. In addition, the FDA designated omacetaxine mepesuccinate as an orphan product because it is intended to treat a rare disease or condition.
Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, stated that the approval of omacetaxine mepesuccinate “provides a new treatment option for patients who are resistant to or cannot tolerate other FDA-approved drugs for chronic or accelerated phases of CML.” He also noted that it “is the second drug approved to treat CML in the past two months.”