TopoTarget and CuraGen Initiate NCI-sponsored Phase II Clinical Trial of PXD101 for Acute Myelogenous Leukemia

TopoTarget A/S (CSE: TOPO) and CuraGen Corp. (Nasdaq: CRGN) announce the initiation of patient dosing in a National Cancer Institute (NCI) sponsored Phase II clinical trial evaluating the activity of PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in the treatment of Acute Myelogenous Leukaemia (AML). The trial will be conducted at multiple sites in the United States.

Patients under the age of 60 with relapsed or refractory AML, or patients over 60 with newly diagnosed or previously treated AML are eligible for enrollment in the open-label trial. Up to 55 patients will be enrolled and receive three week cycles of PXD101 administered by intravenous infusion. Patients demonstrating complete or partial response, as defined by the Revised Recommendations of the International Working Group, will continue to receive treatment with PXD101 until disease progression. The primary endpoint for the study is response rate, with secondary endpoints measuring overall survival and time to treatment failure.

Kenneth A. Foon, M.D., Director of Clinical Investigations at the University of Pittsburgh Cancer Institute and Principal Investigator of the trial stated “Approximately 80% of AML patients who respond to first line treatments ultimately relapse and have limited treatment options. For patients over the age of 60, the available treatments have significant adverse events that can limit their use in this patient population. We are therefore very interested in learning more about the role that HDAC inhibitors, such as PXD101, can play in the treatment of relapsed AML and as a first-line therapy for AML patients over the age of 60.”

Dr Foon will be working in collaboration with Mark Kirschbaum, M.D., Director of New Drug Development at City of Hope in Duarte, California, who commented “In preclinical experiments, PXD101 shows potent growth inhibitory activity on leukaemic cell lines. The research we have conducted on HDAC inhibitors at the City of Hope suggests that agents like PXD101 affect many of the critical pathways cancer cells use for survival. Based on these intriguing results we look forward to evaluating the role of PXD101 in the treatment of AML.”

Correlative pharmacodynamic studies will also be conducted to evaluate the inhibition of HDACs in AML cells from patients treated with PXD101. Evaluation of the genes regulating proliferation and apoptosis (programmed cell death) and the differential gene expression in AML cells obtained both prior to and following treatment with PXD101 will also be performed.

Peter Buhl Jensen, CEO of TopoTarget, commented:

“I am delighted to announce this study soon after we initiated the first NCI-sponsored PXD101 programme, which is a Phase I study to determine its safety and tolerability in combination with bortezomib (Velcade®). We anticipate the start of further NCI-sponsored trials during the year and these will run in tandem with the multiple Phase II and Phase Ib/II clinical trials that we are progressing with CuraGen. The latter studies are evaluating the therapy’s potential in the treatment of multiple myeloma, T-cell lymphomas, ovarian cancer and colorectal cancer and we aim to report the first preliminary results from mid-2006.”

The trial is being sponsored by the NCI under a Clinical Trials Agreement with CuraGen for PXD101.