PXD101: A Small Molecule HDAC Inhibitor for Advanced Solid Tumors
May 17, 2005, 08:43, Reviewed by: Dr.
|"We are very pleased with the preliminary data from this Phase I trial for solid tumors, as well as the data indicating that both IV and oral dosing are potential routes of administration for PXD101. We are also encouraged by the fact that we see evidence of prolonged activity with this drug, observing histone hyperacetylation, a measure of drug target activity, for up to 24 hours after administration."
CuraGen Corporation (Nasdaq: CRGN - News) and TopoTarget A/S announced that preliminary Phase I data on PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of advanced solid tumors were presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida.
This Phase I open-label study was designed to determine the safety, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of intravenously administered PXD101, as well as initial assessment of the pharmacokinetics of orally administered PXD101.
PXD101 was administered as a single agent to patients with advanced solid tumors whose disease was refractory to standard therapy or for whom no standard therapy existed.
Preliminary data reported on 28 patients receiving PXD101 suggests that this compound is well-tolerated following intravenous and oral administration.
The most common adverse events were fatigue, nausea, vomiting and phlebitis. No hematological toxicities were noted. Clinical investigators described toxicities as mild with no grade 4 toxicity observed.
Histone hyperacteylation, a biomarker of the activity of PXD101 on its target, was noted to increase proportionally with dose escalation and lasted from 6-24 hours after administration. To date, disease stabilization lasting four cycles or longer (range 4 to 8 cycles) was noted in 5 of 28 patients.
"We are very pleased with the preliminary data from this Phase I trial for solid tumors, as well as the data indicating that both IV and oral dosing are potential routes of administration for PXD101," stated Timothy M. Shannon, M.D., Executive Vice President Research and Development and Chief Medical Officer at CuraGen. "We are also encouraged by the fact that we see evidence of prolonged activity with this drug, observing histone hyperacetylation, a measure of drug target activity, for up to 24 hours after administration."
Based upon these Phase I results and recently reported preclinical data, a Phase Ib study evaluating PXD101 plus 5-fluorouracil (5-FU) for the treatment of solid tumors, including colorectal cancer, will begin enrolling patients by the third quarter of 2005. Furthermore, additional proof-of-concept studies for other types of solid tumors will be initiated throughout 2005 evaluating PXD101 either alone or in combination with other active anti-cancer treatments.
The companies also reported than an abstract discussing a second Phase I clinical trial of PXD101 for patients with advanced hematologic cancers, such as multiple myeloma, was published in the ASCO 2005 Proceedings. Preliminary results from this Phase I study suggest safety and tolerability similar to those reported for patients with advanced solid tumors. CuraGen and TopoTarget anticipate that additional results from this ongoing trial will be presented at a medical conference during 2005. The findings of this study are being further explored in the ongoing Phase II clinical trial for patients with advanced multiple myeloma, a deadly form of blood cancer. This Phase II clinical trial is expected to be complete by mid-2006. Additional proof-of- concept studies in other hematologic cancers will also be initiated in 2005.
About HDAC inhibitors
A growing body of research highlights the role of histone deacetylases (HDAC) in regulating gene expression, particularly the expression of cancer- related genes. 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 phenotype when used in combination with other anti-cancer agents. HDAC inhibitors are believed to play a role in a wide range of solid malignancies such as breast, colon, lung and ovarian cancers, and hematological malignancies, such as lymphomas, leukemias and myeloma.
- The data were presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida.
Reprints of the poster presentation and published abstracts, as well as information about ongoing clinical trials are available on the Company's website, www.curagen.com, or by emailing [email protected]
CuraGen Corporation (Nasdaq: CRGN - News) is a genomics-based pharmaceutical company dedicated to improving the lives of patients by developing a pipeline of novel protein, antibody, and small molecule therapeutics in the areas of oncology, inflammatory diseases, and diabetes. CuraGen has established broad development alliances with Abgenix, TopoTarget, and Bayer, and its experienced preclinical and clinical teams are advancing the Company's pipeline of products for unmet medical needs. The Company is headquartered in New Haven and Branford, CT. For additional information please visit http://www.curagen.com.
TopoTarget is a biopharmaceutical company dedicated to delivering new and improved therapeutics for the treatment of cancer. The Company is headquartered in Copenhagen, Denmark and has significant subsidiaries in the UK and Germany. TopoTarget plans to launch its lead product Savene(TM) in Europe and USA in 2006 subject to securing regulatory approval and has a strong pipeline, with a further seven product candidates in clinical development.
TopoTarget's broad pipeline comprises both novel pharmaceuticals and new indications for existing compounds and has been developed based on the Company's precise and in-depth understanding of the molecular mechanisms of cancer combined with its wide experience in clinical oncology practice. TopoTarget is among the leaders in the field of HDAC inhibition, a new and exciting area of anti-cancer research where the Company has developed the new chemical entity PXD101. PXD101, which is in Phase II clinical trials, is being developed in conjunction with the US company, CuraGen Corporation (CRGN). The US National Cancer Institute is sponsoring selected clinical trials of this compound.
TopoTarget was formed in 2000 and has grown both organically and through acquisitions. In 2002, the Company acquired Prolifix Ltd. in the UK and this was followed in 2005 with the purchase of G2M Cancer Drugs AG in Germany. These acquisitions have extended TopoTarget's product portfolio as well as its oncology drug discovery and development capabilities. TopoTarget currently employs 65 people. For more information refer to http://www.topotarget.com.
This press release contains forward-looking statements including statements about data indicating that both IV and oral dosing are potential routes of administration for PXD101; CuraGen's expectation that its Phase Ib clinical trial of PXD101 and 5-FU will begin enrolling patients by the third quarter of 2005; CuraGen's expectation that it will initiate additional proof- of-concept studies for other types of solid tumors throughout 2005 evaluating PXD101 either alone or in combination with other active anti-cancer treatments; CuraGen and TopoTarget's anticipation that additional results from a second Phase I clinical trial of PXD101 will be presented at a medical conference during 2005; CuraGen's expectation that a Phase II clinical study for patients with advanced multiple myeloma will be complete by mid-2006; CuraGen's expectation that additional proof-of-concept studies in other hematologic cancers will be initiated in 2005; NCI's sponsorship of several additional clinical trials to investigate PXD101 for the treatment of various cancers, both as a single-agent and in combination chemotherapy regimens; and TopoTarget's aim to identify and market new indications for existing compounds. We caution investors that there can be no assurance that actual results or business conditions will not differ materially from those projected or suggested in such forward-looking statements as a result of various factors, including, but not limited to, the following: the risk that any one or more of the drug development programs of CuraGen and/or TopoTarget will not proceed as planned for technical, scientific or commercial reasons or due to patient enrollment issues or based on new information from nonclinical or clinical studies or from other sources; the success of competing products and technologies; technological uncertainty and product development risks; uncertainty of additional funding; CuraGen's history of incurring losses and the uncertainty of achieving profitability; CuraGen's stage of development as a genomics-based pharmaceutical company; government regulation; patent infringement claims against CuraGen's products, processes and technologies; the ability to protect CuraGen's patents and proprietary rights; uncertainties relating to commercialization rights; and product liability exposure. Please refer to CuraGen's Annual Report on Form 10-K for the period ended December 31, 2004 for a complete description of these risks. CuraGen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, unless required by law.
Glenn Schulman, PharmD, MPH
Dr. Peter Buhl Jensen, MD, PhD, CEO
+ 45 21 60 89 22
Tim Corcoran, COO
+ 44 787 656 1027
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