Omacetaxine mepesuccinate

Omacetaxine mepesuccinate (INN, or homoharringtonine, trade name Omapro) is an alkaloid from Cephalotaxus harringtonia that is investigated for potential use as a drug against hematological cancers. It is being developed by ChemGenex and is on fast track approval schedule in the United States. Omacetaxine has been granted orphan drug status in the U.S. and in Europe.

Mechanism of action
Omacetaxine induces apoptosis by inhibition of protein synthesis, particularly Mcl-1. It has a different point of action than tyrosine kinase inhibitors like imatinib, and has potential therapeutic advantages for patients who have developed resistance to tyrosine kinase inhibitor therapy.

Studies
In vitro and animal model trials showed that omacetaxine has potential to treat resistant leukemia mainly chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL).

In June 2009, results of a long-term open label Phase II study were published, which investigated the use of omacetaxine infusions in CML patients. After twelve months of treatment, about one third of patients showed a cytogenetic response. A study in patients who had failed imatinib and who had the drug resistant T315I mutation achieved cytogenetic response in 28% of patients and hematological response in 80% of patients, according to preliminary data.

Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome (MDS, 25 patients) and acute myelogenous leukemia (AML, 76 patients). Patients with solid tumors did not benefit from omacetaxine.