CuraGen and TopoTarget Initiate Phase I/II Clinical Trial of Belinostat (PXD101) Combination Therapy for Acute Myeloid Leukemia
BRANFORD, Conn., Aug. 28 -- CuraGen Corporation and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) announced today the initiation of patient dosing in a Phase I/II clinical trial evaluating belinostat (PXD101), a histone deacetylase (HDAC) inhibitor, in combination with the anthracycline idarubicin for the treatment of Acute Myeloid Leukemia (AML). The trial is being conducted at multiple sites in the European Union.
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 trial. Initially, 24 to 40 patients will be enrolled into one of two treatment arms and receive intravenous treatment with a combination of belinostat and idarubicin. Patients will receive standard doses of idarubicin in combination with either belinostat administered intravenously once daily for five days, or a continuous infusion of belinostat over 24 to 48 hours. Enrollment into the arms will occur in parallel in order to assess safety and define the maximum tolerated dose (MTD) for each treatment regimen. Upon establishing the MTD for each treatment arm, the trial will be advanced into Phase II to further define the safety and efficacy of belinostat in combination with standard doses of idarubicin.
Patients demonstrating complete or partial response, as defined by the Revised Recommendations of the International Working Group, will continue to receive treatment with belinostat until disease progression. The primary objectives for the study include safety, tolerability, and efficacy for each treatment regimen. Secondary objectives include time to response, duration of response, and survival.
The trial will also include pharmacokinetic and pharmacodynamic studies to evaluate the inhibition of HDAC enzymes in AML cells from patients treated with belinostat. 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 belinostat will also be performed.
The trial is being led by Dr. Richard Schlenk, University Hospital of Ulm, Germany, in collaboration with clinical investigators in Germany, France and the UK.
"In preclinical studies, belinostat has shown potent growth-inhibitory activity on leukemic cell lines, and there is evidence that belinostat has an additive effect when combined with anthracyclines. 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 side effects 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 belinostat, can play in the treatment of AML," commented Dr. Frank Armstrong, President and Chief Executive Officer of CuraGen.
About Acute Myeloid Leukemia (AML)
Approximately 14,000 cases of AML, the most common type of acute leukemia, are expected to be diagnosed in the United States during 2007 with more than 9,000 deaths attributed to this disease. The average age of a person diagnosed with AML is 65 years, with men more likely than women to develop AML. Several chemotherapeutic agents are currently used to treat AML and can lead to initial response rates above 50%. However, the five-year survival for AML patients under the age of 65 is approximately 33%, while patients over 65 years have a five-year survival rate of less than 5%. While some patients may remain in remission for extended periods of time, the majority of AML patients relapse, highlighting the need for improved therapies for the treatment of this disease.
About Belinostat (PXD101)
Belinostat is a promising small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid tumors and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents, including carboplatin, paclitaxel, cis-retinoic acid, azacitidine 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.
Intravenous belinostat is currently being evaluated in multiple clinical trials as a potential treatment for cutaneous and peripheral T-cell lymphomas, B-cell lymphomas, AML, mesothelioma, soft tissue sarcoma, MDS, and liver, colorectal, and ovarian cancers, either alone or in combination with anti- cancer therapies. An oral formulation of belinostat is also being evaluated in a Phase I clinical trial for patients with advanced solid tumors. In August 2004, CuraGen signed a Clinical Trials Agreement with the NCI under which the NCI will sponsor several clinical trials to investigate belinostat for the treatment of various cancers, both as a single-agent and in combination chemotherapy regimens. In May 2005, TopoTarget announced the signing of a Cooperative Research and Development Agreement (CRADA) with the NCI to conduct preclinical and nonclinical studies on belinostat in order to better understand its anti-tumor activity and to provide supporting information for clinical trials.
About CuraGen
CuraGen Corporation is a dedicated clinical-stage biopharmaceutical company developing diverse approaches, including novel protein, antibody, antibody-drug conjugate and small molecule therapeutics for the treatment of cancer and for cancer supportive care. CuraGen is currently conducting clinical trials to investigate the potential of velafermin, belinostat and CR011-vcMMAE. By leveraging the drug development strengths cultivated over the years, CuraGen expects to make a difference by advancing its promising therapeutics to address the unmet medical needs of cancer patients. CuraGen Corporation is headquartered in Branford, Connecticut. For additional information please visit http://www.curagen.com .
About TopoTarget
TopoTarget (OMX - The Nordic Exchange: TOPO) is a biopharmaceutical company, headquartered in Denmark and with subsidiaries in the UK, Germany and the USA, 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 highly predictive cancer models and key cancer enzyme regulators (mainly HDAC, mTOR, and topoisomerase II inhibitors) and a strong development foundation has been built. TopoTarget has a broad portfolio of small molecule preclinical drug candidates and seven drugs are in clinical development, including both novel anti-cancer therapeutics and new cancer indications for existing drugs. Savene(TM) is TopoTarget's first product on the market. In addition to organic growth, TopoTarget consistently looks for opportunities to strengthen and expand its
activities through acquisitions and in-licensing. For more information, please refer to http://www.topotarget.com .
Safe Harbor
Statements in this press release regarding management's future expectations, beliefs, intentions, goals, strategies, plans or prospects, including statements relating to the expected benefits of belinostat, the use of belinostat in the treatment of AML and other diseases, and the conduct, enrollment, and data relating to CuraGen's Phase I/II clinical trial for belinostat may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Such forward-looking statements involve known and unknown risks, uncertainties and other factors including the risk that any one or more of CuraGen's drug development programs 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, CuraGen's stage of development as a biopharmaceutical company, government regulation and healthcare reform, technological uncertainty and product development risks, product liability exposure, uncertainty of additional funding, CuraGen's history of incurring losses and the uncertainty of achieving profitability, reliance on research collaborations and strategic alliances, competition, patent infringement claims against CuraGen's products, processes and technologies, CuraGen's ability to protect its patents and proprietary rights and uncertainties relating to commercialization rights, as well as those risks, uncertainties and factors more fully disclosed in the 'Risk Factors' section of CuraGen's Quarterly Report on Form 10-Q for the quarter ended June 30, 2007, filed with the Securities and Exchange Commission, as well as other documents that may be filed by CuraGen from time to time with the Securities and Exchange Commission. As a result of such risks, uncertainties and factors, CuraGen's actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. CuraGen is providing the information in this press release as of this date and assumes no obligations to update the information included in this press release or revise any forward-looking statements, whether as a result of new information, future events or otherwise.