CuraGen and TopoTarget announce NCI-sponsored Phase II clinical trial with PXD101 for AML

07-06-2006

CuraGen Corporation (CRGN) and TopoTarget A/S (TOPO) announced the initiation of patient dosing in a Phase II clinical trial evaluating the activity of PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of acute myelogenous leukemia (AML).

This trial is being sponsored by the National Cancer Institute (NCI) under a Clinical Trials Agreement with CuraGen for PXD101 and will be conducted at multiple sites in the United States.

The Phase II clinical trial is an open-label study being led by Kenneth A. Foon, MD, director of clinical investigations at the University of Pittsburgh Cancer Institute, in collaboration with Mark Kirschbaum, MD, director of new drug development at City of Hope in Duarte, California. Patients under the age of 60 with relapsed or refractory AML, or patients over 60 with newly diagnosed or with relapsed or refractory AML are eligible for enrollment.

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.

"In preclinical experiments, PXD101 shows potent growth inhibitory activity on leukemic cell lines. The research we have conducted on HDAC inhibitors at City of Hope suggests that agents like PXD101 affect many of the critical pathways cancer cells use for survival," stated Kirschbaum. "Based on these intriguing results we have initiated patient treatment with PXD101 and look forward to evaluating the role of this HDAC inhibitor for the treatment of AML."

"Approximately 80% of AML patients who respond to first line treatments ultimately relapse and then have limited treatment options. For patients over the age of 60, the available treatments have significant adverse effects that can limit their use in this patient population," stated Foon. "We are therefore very interested in learning more about the role that HDAC inhibitors, such as PXD101, can play in the treatment of AML and expect to treat patients at the University of Pittsburgh Cancer Institute in the coming months."

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

PXD101 is a promising small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents, including 5-fluorouracil (5-FU), carboplatin, paclitaxel and Velcade(R) (bortezomib) for Injection. HDAC inhibitors represent a new mechanistic class of anti-cancer therapeutics that target HDAC enzymes and have been shown to: arrest growth of cancer cells (including drug resistant subtypes); induce apoptosis, or programmed cell death; promote differentiation; inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance when used in combination with other anti-cancer agents.

PXD101 is currently being evaluated in multiple clinical trials as a potential treatment for multiple myeloma, T-cell lymphoma, and colorectal and ovarian cancers, either alone or in combination with anti-cancer therapies. In August 2004, CuraGen signed a Clinical Trials Agreement with the NCI under which the NCI will sponsor several clinical trials to investigate PXD101 for the treatment of various cancers, both as a single agent and in combination chemotherapy regimens. In May 2005, TopoTarget signed a Cooperative Research and Development Agreement (CRADA) with the NCI to conduct pre-clinical and non-clinical studies on PXD101 in order to better understand its anti-tumor activity and to provide supporting information for clinical trials.

CuraGen Corporation, headquartered in Branford, Connecticut, is a biopharmaceutical company developing diverse approaches, including novel protein, antibody, and small molecule therapeutics, that aim to offer hope for patients with cancer, inflammatory diseases, and diabetes.

TopoTarget is a fully integrated biopharmaceutical company, headquartered in Denmark and with subsidiaries in the U.K. and Germany, and dedicated to finding "Answers for Cancer" and developing improved cancer therapies. TopoTarget is founded and run by clinical cancer specialists and combines years of hands-on clinical experience with in-depth understanding of the molecular mechanisms of cancer. Focus lies on key cancer enzyme regulators (mainly HDAC, mTOR, and topoisomerase II inhibitors) and a strong development foundation of proprietary, highly predictive cancer models has been built.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2006, Biotech Business Week via NewsRx.com.