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

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.

• Authors: Aziz Nazha, Hagop Kantarjian, Jorge Cortes, Alfonso Quintás-Cardama
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 14 Issue 14 Pg. 1977-86 (Oct 2013) ISSN: 1744-7666 [Electronic] England
• PMID: 23875628 (Publication Type: Journal Article, Review)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents, Phytogenic
• Harringtonines
• Homoharringtonine

Topics

• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Harringtonines (pharmacology, therapeutic use)
• Homoharringtonine
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)