FDA Approval for Omacetaxine Mepesuccinate
Brand name(s): Synribo®
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.
On October 26, 2012, the Food and Drug Administration (FDA) granted accelerated approval to omacetaxine mepesuccinate (Synribo® for Injection for subcutaneous use, made by 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 that enrolled patients with CML in chronic phase (CML-CP) or 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) was the primary endpoint for CML-CP, and major Hematologic Response (MaHR) was the primary endpoint for CML-AP. MCyR was achieved in 18.4 percent of patients with CML-CP (median response duration, 12.5 months), and MaHR was achieved in 14.3 percent of patients with CML-AP (median response duration, 4.7 months).
Safety data were evaluated in 163 patients (108 patients with CML-CP and 55 patients with CML-AP) who received at least one dose of omacetaxine mepesuccinate. Four additional patients with CML-CP from another open-label single-arm trial of omacetaxine mepesuccinate were included in the safety analysis. The most common (at least 20 percent) grade 1-4 adverse reactions in the combined safety population were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia. The most common (at least 5 percent) grade 3-4 adverse reactions were thrombocytopenia, anemia, neutropenia, febrile neutropenia, asthenia/fatigue, pyrexia, and diarrhea.
Ten deaths were reported within 30 days of the last omacetaxine mepesuccinate dose. Four of the deaths were attributed to progressive disease, four to cerebral hemorrhage, one to multi-organ failure, and one to unknown causes.
The recommended starting dose and schedule for induction with omacetaxine mepesuccinate is 1.25 mg/m2 subcutaneous injection twice daily for 14 days of a 28-day cycle. The recommended maintenance dose and schedule is 1.25mg/m2 subcutaneous injection twice daily for 7 days of a 28-day cycle.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.