ChemGenex Launches Multinational Phase 2/3 Study for CML Patients with the T315I Mutation Reports Preclinical activity in T315I CML
MELBOURNE, Australia, and MENLO PARK, California U.S.A. (June 13, 2006).
ChemGenex Pharmaceuticals (ASX: CXS, NASDAQ: CXSP) announced today that it has launched a new multi-national phase 2/3 study evaluating the use of Ceflatonin® (homoharringtonine, HHT) in patients with chronic, accelerated and blast-phase chronic myeloid leukemia (CML) who have the T315I bcr-abl point mutation, which is associated with resistance to Gleevec® and two known tyrosine kinase inhibitors (TKIs) currently under development.
The study will be conducted in both the United States and Europe and is projected to enroll up to 81 patients within 12 months. The primary endpoint will be hematologic response rate, and the secondary endpoint will be cytogenetic response rate.
"This new study offers hope to a growing number of CML patients who have developed the T315I bcr-abl point mutation, against which both Gleevec®, and two investigational TKI's, are ineffective," said Greg Collier, Ph.D., Chief Executive Officer and Managing Director of ChemGenex. "Ceflatonin® has recently shown preclinical activity in CML cell lines with the T315I mutation and has already demonstrated clinical activity in human clinical studies for patients failing Gleevec®. Demonstration of positive results in CML patients with the T315I mutation may serve as the basis for filing for an NDA with the FDA under an accelerated approval, based on a high level of unmet medical need."
In other developments, a recent preclinical study presented at the American Association of Cancer Research conference showed that Ceflatonin® is active as a single-agent and in-combination with other agents, including imatinib (Gleevec®), in CML cell lines with the T315I bcr-abl point mutation. The research was conducted by Professor William Plunkett, Ph.D., Department of Experimental Therapeutics at the University of Texas, M.D. Anderson Cancer Center.
Clinical Trial Details
The trial will be a multi-national open-label study which will open initially at the M.D. Anderson Cancer Center in Houston, Texas USA, the University of Heidelberg in Germany, and the Hospital Edouard Herriott in Lyon, France. The trial will expand to approximately 16 additional centers in both the United States and Europe.
In the remission induction phase, patients will receive 1.25 mg/m2 HHT by subcutaneous injection two times a day for 14 consecutive days, with cycles repeated every 28 days. In the remission maintenance phase, patients will receive 1.25 mg/m2 HHT by subcutaneous injection two times a day for 7 consecutive days, with cycles repeated every 28 days. Patients will be stratified upon whether they have chronic phase (CP), accelerated phase (AP), or blast phase (BP) CML. The study will be conducted in two stages, using a Simon two-stage study design for each patient subpopulation. During the first stage, 13 evaluable patients from each patient subpopulation (CP, AP, BP CML) will be enrolled. If one or more responses are seen during the first stage of a subpopulation, another 14 evaluable patients from that subpopulation will be enrolled in the second stage. It is anticipated that a maximum of 81 patients will be enrolled into the study, if all three subpopulations proceed to the second stage. The primary and secondary endpoints are hematologic and cytogenetic response rates, respectively.
About Ceflatonin®
Ceflatonin® (homoharringtonine or HHT) is a potent inducer of apoptosis (programmed cell death) in myeloid cells and inhibits angiogenesis (blood vessel formation). In phase 2 studies, Ceflatonin® demonstrated clinical activity in patients with CML, both as a single agent and in combination with other chemotherapeutic drugs. ChemGenex is developing Ceflatonin® for the treatment of CML, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
Ceflatonin has a different mechanism of action than tyrosine kinase inhibitors (TKIs), which are widely used in the treatment of CML. A registration-directed, international phase 2/3 clinical study is currently in progress, investigating the effectiveness of Ceflatonin® in the treatment of CML patients who have developed resistance to TKI therapy due to the T315I Bcr-Abl point mutation. Ceflatonin® was recently granted Fast Track status by the U.S. Food and Drug Administration (FDA) for this clinical indication. Additional studies will assess the activity of Ceflatonin® in CML patients who are refractory to, or intolerant of treatment with TKIs and investigate if combination therapy with Ceflatonin®, TKIs and other agents increases the cytogenetic and molecular response rates in CML patients.
Ceflatonin® is not approved by the FDA as a treatment in any indication and is being evaluated in clinical trials for efficacy and safety for future regulatory applications.
About Chronic Myeloid Leukemia
Chronic myeloid leukemia (CML) is a cancer of the blood cells caused in the majority of cases by an acquired genetic defect called the bcr-abl mutation. This defect occurs when genetic material from two chromosomes (9 and 22) swaps places, creating the so-called Philadelphia chromosome. The bcr-abl mutation interferes with normal cell replication processes, leading to an abnormal proliferation of white blood cells.
CML usually occurs in adults and typically progresses through three phases. Patients generally are diagnosed in ‘chronic phase', progress through ‘accelerated phase' and then may die if the disease progresses to ‘blast phase'. CML incidence is relatively consistent, occurring at about 1 to 2 per 100,000 people, and the global CML market for therapeutics is significant.
Patients with chronic phase CML have been effectively treated in recent years by the drug imatinib mesylate (Gleevec). However, over time, some patients may become resistant to the therapeutic effects of the drug, and the disease then progresses.
Gleevec® is a registered trade-mark of Novartis AG.
About ChemGenex Pharmaceuticals Limited
ChemGenex Pharmaceuticals is a pharmaceutical development company dedicated to improving the lives of patients by developing therapeutics in the areas of oncology, diabetes, obesity, and depression. ChemGenex harnesses the power of genomics for target discovery and validation, and in clinical trials to develop more individualized therapeutic outcomes. ChemGenex's lead compound, Ceflatonin®, is currently in phase 2/3 clinical trials for chronic myeloid leukemia and Quinamed® is in phase 2 clinical development for prostate, breast and ovarian cancers. The company has a significant portfolio of anti-cancer, diabetes, obesity and depression programs, several of which have been partnered with international pharmaceutical companies. ChemGenex currently trades on the Australian Stock Exchange under the symbol "CXS" and on NASDAQ under the symbol "CXSP".
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