Emerging Drug Therapies

These are exciting days in the CML Community as more and more options are making their way into the patient's tool chest.  Many of the drugs and therapies listed below are either currently in clinical trials or soon to be.  This page will be updated regularly as information becomes available.

Stemline Therapeutics - SL-401  SL-401, a novel therapeutic argeting the interleukin-3 receptor (IL-3R) that is overexpressed on the CSCs and tumor bulk of a wide range of hematologic cancers, is entering pivotal clinical trial programs for BPDCN and AML, as well as clinical evaluations in several other hematologic malignancies (including CML). SL-401 has been shown to be well-tolerated and non-toxic to the bone marrow.

At the 2013 meeting of the European Society of Hematology/International CML Foundation, MD Anderson Cancer Center presented studies detailing SL-401's notable activitiy against CML primary blasts and cancer stem cells (CSCs) in animal models and in vitro. SL-401 significantly reduced the growth of CML blasts, as well as CSCs from patients with tyrosine kinase inhibitor (TKI)-resistant CML. Additionally, the combination of SL-401 and the TKI, imatinib, had a significant synergistic effect on inhibiting the growth of primary CML cells from patients. SL-401 also prolonged the survival of mice inoculated with primary cells from a CML patient in blast crisis who was resistant to several TKIs.

ARIAD Pharmaceuticals - Ponatinib/Iclusig  FDA APPROVED!   ARIAD’s second oncology product candidate, ponatinib, is an internally discovered oral multi-targeted kinase inhibitor that we believe has broad potential applications in cancer. Ponatinib has been evaluated in a pivotal Phase 2 registration trial in patients with resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL). The PACE (Ponatinb Ph+ ALL and CML Evaluation) trial was designed to provide definitive clinical data for regulatory approval in this setting. [NOTE: the PACE trial is currently closed. Ponatinib is available via compassionate use for those that qualify. Please contact us for additional information on availability.]

TEVA - Omacetaxine Mepessuccinate/Synribo  FDA APPROVED!   Omacetaxine mepessuccinate is a first-in-class small molecule which, as a single agent, is being evaluated in clinical trials in a range of hematological malignancies. Omacetaxine has a novel mode of action, and induces apoptosis (cell death) by inhibition of protein synthesis, particularly Mcl-1.  As Omacetaxine acts independently of tyrosine kinase inhibitors, it may have therapeutic advantages for patients who have developed resistance to tyrosine kinase inhibitor therapy.  Omacetaxine is administered subcutaneously.

Pfizer - Bosutinib/Bosulif® FDA APPROVED!  Bosutinib is a third generation tyrosine kinase inhibitor. Having recently being approved, the drug continues to look very promising. It has been useful in patients whose leukemia is resistant to both first and second generation tyrosine kinase inhibitors. It is a dual kinase inhibitor. Unlike imatinib, bosutinib inhibits the autophosphorylation of both Abl and Src kinases, resulting in inhibition of cell growth and apoptosis (cell death).

CytRx - Bafetinib (formerly INNO-406)
Bafetinib is a potent, orally available, rationally designed, dual Bcr-Abl and Lyn kinase inhibitor, which was developed as a third-line treatment for patients with CML and certain forms of acute myeloid leukemia (AML) that are refractory or intolerant of other approved treatments.  In a Phase 1, dose-ranging clinical trial, Bafetinib demonstrated clinical responses in patients with CML and other leukemias that have the Philadelphia Chromosome that have proven intolerant of, or resistant to Gleevec® and, in some cases, second-line therapies.

Deciphera - DCC-2036
DCC-2036 is a novel small molecule inhibitor which was designed to bind within an unique region of BCR-ABL kinase known as the ‘switch pocket’. This unique mode of action enables DCC-2036 to retain high potency against major clinically resistant mutations (including the gatekeeper T315I mutation) which can lead to drug resistance and disease recurrence.   Preclinical data summarizing these properties of DCC-2036 have been accepted for publication in the journal Cancer Cell and published online on April 12, 2011.  DCC-2036 is orally bio-available and has a narrow spectrum of kinase inhibition.  A current Phase 1 study in patients with Philadelphia positive (Ph+) chronic myelogenous leukemia (CML) is nearing completion. For more information on trials for this drug, visit http://clinicaltrials.gov/ct2/show/NCT00827138

Nerviano Medical Sciences - Danusertib
Danusertib is an Aurora Kinase Inhibitor which also shows inhibitory activity against the Bcr-Abl tyrosine kinase, including its multidrug-resistant T315I mutant.  This mutation is responsible for up to 25% of all clinically observed resistances in CML patients undergoing Imatinib therapy.  The combined kinase inhibition of Danusertib represents a promising new strategy for Bcr-Abl positive leukemias Aurora are a family of serine/threonine kinases acting as key mitotic regulators required for genome stability.  Aurora are involved in regulating multiple steps in mitosis, including centrosome duplication, formation of a bipolar mitotic spindle, and chromosome alignment on the mitotic spindle.