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Medical Areas: Hematology | Oncology
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Synribo (omacetaxine mepesuccinate)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Teva Pharmaceutical
Approval Status: Approved October 2012
Treatment Area: chronic or accelerated phase chronic myeloid leukemia
Synribo (omacetaxine mepesuccinate) is a cephalotaxine ester. It is a protein synthesis inhibitor and is independent of direct Bcr-Abl binding.
Synribo is specifically approved for the treatment of adults with chronic or accelerated phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors.
Synribo is supplied as a solution for subcutaneous administration. The recommended initial dose of the drug is as follows: Induction Schedule: 1.25 mg/m2 administered subcutaneously twice daily for 14 consecutive days every 28 days, over a 28-day cycle. Cycles should be repeated every 28 days until patients achieve a hematologic response. Maintenance Dosing: 1.25 mg/m2 administered subcutaneously twice daily for 7 consecutive days every 28 days, over a 28-day cycle. Treatment should continue as long as patients are clinically benefiting from therapy.
The FDA approval of Synribo was based on a combined cohort of adults with CML from two trials. The combined cohort consisted of subjects who had received two or more approved TKIs and had, at a minimum, documented evidence of resistance or intolerance to dasatinib and/or nilotinib. The subjects were treated with omacetaxine mepesuccinate at a dose of 1.25 mg/m2 administered subcutaneously twice daily for 14 consecutive days every 28 days (induction cycle). Responders were then treated with the same dose and twice daily schedule for 7 consecutive days every 28 days (maintenance cycle) for up to 24 months.
Chronic Phase CML
A total of 76 subjects were included in the efficacy analysis. The efficacy endpoint was based on major cytogenetic response (MCyR). Fourteen subjects (18.4%) achieved MCyR; 7.9% achieved confirmed complete cytogenic response and 3.9% achieved confirmed partial cytogenic response. The mean time to MCyR onset was 3.5 months and the median duration of MCyR was 12.5 months.
Accelerated Phase CML
A total of 35 subjects were included in the efficacy analysis. The efficacy endpoint was based on major cytogenetic response (MCyR) and MaHR (complete hematologic response [CHR] or no evidence of leukemia [NEL]. Five subjects (14.3%) achieved MaHR; 4 subjects (11.4%) CHR and one (2.9%) NEL. Zero subjects achieved MCyR. The mean time to response onset in the 5 subjects was 2.3 months and the median duration of MaHR was 4.7 months.
Adverse events associated with the use of Synribo may include, but are not limited to, the following:
- injection site reaction
Mechanism of Action
Synribo (omacetaxine mepesuccinate) is a cephalotaxine ester. It is a protein synthesis inhibitor and is independent of direct Bcr-Abl binding. Omacetaxine mepesuccinate binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaeabacteria. In vitro, omacetaxine mepesuccinate reduced protein levels of the Bcr-Abl oncoprotein and Mcl-1, an anti-apoptotic Bcl-2 family member.
Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, Benichou AC, Craig AR, Michallet M, Nicolini FE, Kantarjian H; on behalf of the Omacetaxine 202 Study Group Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood 2012 Sep 27;120(13):2573-2580
For additional information regarding Synribo or chronic or accelerated phase chronic myeloid leukemia, please visit the Synribo web page.