Blood
Histone Deacetylase (HDAC) Inhibitors For Advanced Multiple Myeloma,reaches Phase II
By Akanksha, Pharmacology Correspondent
Feb 2, 2005, 10:58

CuraGen Corporation and TopoTarget A/S today announced the initiation of patient dosing in a Phase II clinical trial evaluating PXD101,a small molecule histone deacetylase (HDAC) inhibitor, as a potential treatment for advanced multiple myeloma, a deadly type of blood cancer.

CuraGen also announced that they have successfully filed an investigational new drug application (IND) for PXD101 to the Food and Drug Administration, allowing initiation of this trial at clinical sites in the United States.

Based on results obtained in Phase I, we are very pleased to advance PXD101 into Phase II and evaluate it as a potential treatment for multiple myeloma," stated William Hahne, M.D., Vice President of Clinical Development at CuraGen. "Throughout 2005, we expect to initiate additional Phase II trials that will investigate PXD101 as a potential treatment for other types of solid and hematologic cancers, and Phase Ib/II studies to explore the safety and activity of PXD101 in combination with other chemotherapy regimens and newer targeted therapies."

This Phase II clinical trial is an open label, multicenter study evaluating the efficacy and safety of PXD101 administered as a single-agent and in combination with dexamethasone, for the treatment of advanced multiple myeloma in patients who have previously failed at least two treatment regimens.

The trial is expected to enroll approximately 50 patients at multiple sites in Europe and the United States. Following enrollment, patients will receive 900 mg/m2/day PXD101 administered intravenously once daily for five consecutive days every three weeks for two cycles. Patients will then be evaluated for tumor response by standard criteria and will either continue receiving up to eight cycles of PXD101 if they demonstrate response or stable disease, or begin combination therapy consisting of PXD101 and dexamethasone. The study is expected to be complete by mid 2006.

Multiple myeloma (MM) is a progressive cancer arising from a particular type of blood cell, called plasma cells. It is the second most prevalent blood cancer in the U.S. with nearly 50,000 individuals suffering from MM, and more than 15,000 new cases expected to be diagnosed this year.

MM is characterized by excessive numbers of abnormal plasma cells in the bone marrow and the overproduction of abnormal immunoglobulins. As a result of MM, patients may develop bone lesions, anemia, elevated blood calcium levels, kidney damage, and a decreased ability to fight off infections. Despite the availability of treatments for MM, there is currently no cure for this disease.

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, and is currently being evaluated in a Phase II clinical trial for the treatment of multiple myeloma.

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.

In August 2004, CuraGen signed a Clinical Trials Agreement with the National Cancer Institute (NCI) under which the NCI will sponsor several additional clinical trials to investigate PXD101 for the treatment of various cancers, both as a single-agent and in combination chemotherapy regimens.
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TopoTarget is a British/Danish biopharmaceutical company dedicated to the discovery, development and clinical progression of new and improved therapeutics for the cancer patient. The Company was created by the merger of TopoTarget A/S, the Danish oncology company and Prolifix Ltd, the UK based cell cycle company. TopoTarget develops novel pharmaceuticals and aims to identify and market new indications for existing compounds. It applies its precise and in-depth understanding of the molecular mechanisms of cancer with its wide experience in clinical oncology practice to develop new and effective medicines to combat the disease. TopoTarget is based in Copenhagen, Denmark and Oxford, UK. For more information refer to the company's website.

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