Omacetaxine has an interesting history. It is a synthetic form...

Omacetaxine has an interesting history.

It is a synthetic form of a chemotherapy drug that has been around for 30+ years, HHT - but it had to be given intravenously and was more toxic. Omacetaxine is less toxic and has the advantage of being given subcutanously - by the patient if needed.

When a patient has CML - they get treated with the first couple of therapies, usually Imatinib (Gleevac) and then if they fail that they try one of the second line drugs such as Dasatinib (in some cases especially if young, they have a bone marrow transplant). If they are using the drugs then they kill as many tumour cells as they can - but will select out the mutating tumour cells who have the T13151 mutation (as those cells are not killed by the Gleevac and other drugs) - and the cells that have the T13151 mutation become the dominant CML cell population.

So the argument seems to be - you have to show the mutation before using the Omacetaxine ... but do you...- you could also argue that they should be trialing it for any failed therapy as it has a different mechanism of action to the other drugs.

If we look at the studies by Cortes: - this is the landmark study we are following:

http://imagesignal.comsec.com.au/asxdata/20091209/pdf/01020877.pdf

but in this paper - the implication is that more is happening.

IDrugs. 2008 May;11(5):356-72.

Omacetaxine mepesuccinate--a semisynthetic formulation of the natural antitumoral alkaloid homoharringtonine, for chronic myelocytic leukemia and other myeloid malignancies.
Quints-Cardama A, Cortes J.

Alfonso Quints-Cardama, MD Anderson Cancer Center, Department of Leukemia, Unit 428, 1515 Holcombe Boulevard, Houston, TX 77030, USA. [email protected]

Abstract
Homoharringtonine (HHT), a natural alkaloid extracted from various Cephalotaxus species, exerts its antitumoral and anti-angiogenic activity through an inhibition of protein synthesis and the promotion of apoptosis. ChemGenex Pharmaceuticals Ltd, in collaboration with Stragen Group, is developing omacetaxine mepesuccinate, a semisynthetic formulation of HHT, as a potential treatment for chronic myelocytic leukemia (CML), myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). In preclinical studies, omacetaxine mepesuccinate induced apoptosis in leukemia cell lines. Results from phase II clinical trials revealed omacetaxine mepesuccinate to be active in patients with CML that was resistant to tyrosine kinase inhibitor (TKI) therapy, including those patients who carry the BCR-ABL1T315I mutation, which is highly insensitive to the TKIs imatinib, nilotinib and dasatinib; the therapeutic was also generally well tolerated. Phase II and III clinical trials are underway to assess the activity of omacetaxine mepesuccinate, either alone or in combination with TKIs or other cytotoxic drugs, in patients with CML that is resistant to TKI therapy. Phase I and II clinical trials for omacetaxine mepesuccinate in the treatment of AML and MDS are also ongoing; intravenous, subcutaneous and oral formulations of the drug are being developed. Omacetaxine mepesuccinate appears to hold potential for the treatment of CML and, in particular, imatinib-resistant CML; the development of alternative formulations of the therapeutic further expands the potential for success in drug development.


I havent worked out how to use bold on HC yet... but the key sentence is:

"Results from phase II clinical trials revealed omacetaxine mepesuccinate to be active in patients with CML that was resistant to tyrosine kinase inhibitor (TKI) therapy, including those patients who carry the BCR-ABL1T315I mutation,"

so there is broader activity in patients with CML without the mutation but resistant to other drugs.

I suspect the problem is that their priority FDA pathway is for the mutation - but there is a lot more to this drug in the short - medium term than just the mutation. They just have to get the FDA approval... somehow.