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.”
Expanded Labeling for Pemetrexed The FDA expanded the labeling of pemetrexed (Alimta, Eli Lilly and Company) to include the results of an additional trial evaluating its safety and efficacy for the initial treatment of patients with locally advanced or metastatic, nonsquamous, non‒small cell lung cancer followed by pemetrexed maintenance in patients with disease that has not progressed after 4 cycles of platinum and pemetrexed as first-line chemotherapy. The approval for expanded labeling was granted on October 17, 2012.
The expanded labeling describes the results of a multicenter, randomized (2:1), double-blind, placebo-controlled trial that evaluated pemetrexed maintenance in patients with stage IIIB/IV nonsquamous, non‒small cell lung cancer whose initial treatment was 4 cycles of pemetrexed plus cisplatin. There were 539 patients randomized to receive 500 mg/m2 pemetrexed intravenously on day 1 of each 21-day cycle (359 patients) or matching placebo (180 patients). All patients had an ECOG performance status of 0 or 1 and had completed 4 cycles of pemetrexed plus cisplatin with a best response of stable disease, partial response, or complete response.
Investigator-assessed progression-free survival (PFS) was significantly improved in patients randomized to receive pemetrexed maintenance, compared with those who received placebo. Median PFS was 4.1 months for patients in the pemetrexed arm and 2.8 months for patients receiving placebo. Overall survival, a secondary end point, also was significantly improved for patients receiving pemetrexed maintenance, with median survival time of 13.9 months, compared with 11.0 months for patients receiving placebo.
Neutropenia, anemia, fatigue, nausea, vomiting, stomatitis, and edema were the most common (>5%) adverse events for patients in the pemetrexed arm. Anemia and neutropenia were the most common severe adverse reactions. Approximately 25% of patients receiving pemetrexed maintenance had treatment reduced or delayed because of toxicity.
Sources http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm325990.htm http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm325895.htm http://www.fda.gov/Drugs/InformationOnDrugs/Approved Drugs/ucm324239.htm
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