Omacetaxine mepesuccinate (synribo)-newly launched in chronic myeloid leukemia

Aziz Nazha, Hagop Kantarjian, Jorge Cortes, Alfonso Quintás-Cardama

Research output: Contribution to journalArticle

Abstract

Introduction: Omacetaxine mepesuccinate (formerly known as homoharringtonine [HHT]) is a natural alkaloid with significant anticancer activity partly through inhibition of protein synthesis and induction of apoptosis. Prior to the development of tyrosine kinase inhibitors (TKIs), HHT was the most active therapy in chronic myeloid leukemia (CML) after interferon failure. Subsequent trials showed that HHT and omacetaxine are active in patients failing several TKIs or carrying the T315I mutation. Areas covered: This review will discuss the preclinical development of HHT and omacetaxine mepesuccinate in CML and the clinical studies leading to its approval by the Food and Drug Administration (FDA). Expert opinion: A sizable number of patients with CML will develop TKI resistance, frequently through the acquisition of BCR-ABL1 kinase domain mutations. Omacetaxine is active in patients with CML after failure to multiple TKIs and in those carrying the T315I mutation, which is highly resistant to all FDA-approved TKIs except for ponatinib. Both ponatinib and omacetaxine have been recently approved by the FDA and represent useful treatment options for patients with CML who failed several TKIs and/or acquired the T315I mutation. The development of an oral formulation of omacetaxine would greatly facilitate its use and provide an attractive option for TKI-based combinatorial strategies.

Original languageEnglish (US)
Pages (from-to)1977-1986
Number of pages10
JournalExpert Opinion on Pharmacotherapy
Volume14
Issue number14
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
United States Food and Drug Administration
Mutation
Expert Testimony
homoharringtonine
Alkaloids
Interferons
Phosphotransferases
Apoptosis
Therapeutics
Proteins

Keywords

  • BCR-ABL1 mutations
  • Chronic myeloid leukemia
  • Homoharringtonine
  • Omacetaxine mepesuccinate
  • T315I

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Omacetaxine mepesuccinate (synribo)-newly launched in chronic myeloid leukemia. / Nazha, Aziz; Kantarjian, Hagop; Cortes, Jorge; Quintás-Cardama, Alfonso.

In: Expert Opinion on Pharmacotherapy, Vol. 14, No. 14, 01.10.2013, p. 1977-1986.

Research output: Contribution to journalArticle

Nazha, Aziz ; Kantarjian, Hagop ; Cortes, Jorge ; Quintás-Cardama, Alfonso. / Omacetaxine mepesuccinate (synribo)-newly launched in chronic myeloid leukemia. In: Expert Opinion on Pharmacotherapy. 2013 ; Vol. 14, No. 14. pp. 1977-1986.
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