MERCK PRESS RELEASE
MEDIA CONTACT: Pamela Eisele (267) 305-7896
Merck’s International Study of Vorinostat (ZOLINZA®) in Patients with Mesothelioma Proceeds to Phase III Development
WHITEHOUSE STATION, N.J., May 27, 2008 – Merck & Co., Inc announced today its international, investigational trial of vorinostat (ZOLINZA ®), the Company's oral histone deacetylase (HDAC) inhibitor, in patients with advanced malignant pleural mesothelioma previously treated with systemic chemotherapy has progressed into Phase III investigation and is currently enrolling patients. The decision to move forward follows the review of currently available safety and efficacy data from the Phase II portion of the trial by the study's independent Data Safety and Monitoring Board (DSMB). The data remains blinded to investigators and Merck researchers.
This ongoing randomized, double-blind, placebo-controlled trial is designed to determine the safety, tolerability and anti-tumor activity of oral vorinostat with best supportive care as compared to best supportive care plus placebo in patients with advanced mesothelioma who have failed or are intolerant to prior chemotherapy, including pemetrexed in combination with either cisplatin or carboplatin. Patients not eligible for or not able to receive pemetrexed may also be considered for enrollment in the trial. The study is expected to enroll 660 patients; the location of current participating centers include the United States, Belgium, Germany, the Netherlands, New Zealand, Spain, Sweden and the United Kingdom.
"With no currently approved regimens for relapsed or refractory mesothelioma, continued research focused on identifying targeted therapies and differentiated approaches is critical," said Eric Rubin, M.D., vice president, oncology clinical research, Merck Research Laboratories. "We are pleased that the investigation of vorinostat for the treatment of advanced mesothelioma has advanced into Phase III development and look forward to the results of this now expanded trial."
Mesothelioma is a type of cancer that begins in the mesothelium, a thin layer of tissue that lines several different organs and spaces inside the body. The most common form is pleura mesothelioma, where tumors form in the tissue that lines the chest cavity. The incidence of malignant pleural mesothelioma is increasing worldwide with approximately 2,000-3,000 new cases of mesothelioma occurring each year in the United States. Although rare, this is a serious, aggressive cancer that often reaches an advanced stage before symptoms appear.
The primary endpoints of the Phase III trial include overall survival as well as characterization of the overall safety and toxicity of vorinostat in patients with advanced malignant mesothelioma. Secondary endpoints include overall objective response, response duration, progression-free survival, the dyspnea score of lung cancer symptom scale modified for mesothelioma (LCSS-Meso) and the percentage change from baseline in forced vital capacity (FVC).
To find out more information about how to become involved in the trial, call toll-free 1-866-890-6619 (in the U.S.) and 1-888-577-8839 (outside of the U.S.) or visit www.merckcancertrials.com for more complete information
Lung cancer clinical program
The clinical development program for vorinostat includes several other ongoing trials in lung cancer, including: a Phase II/III trial of vorinostat in combination with paclitaxel plus carboplatin or placebo in patients with stage IIIB (with pleural effusion) or stage IV non-small cell lung cancer (NSCLC); a Phase II study led by the National Cancer Institute of vorinostat or placebo in combination with carboplatin and paclitaxel for patients with advanced or metastatic NSCLC; and a Phase I trial of vorinostat in combination with gemcitabine plus platinum in patients with advanced NSCLC.
About ZOLINZA
ZOLINZA is a type of anticancer medicine called an HDAC inhibitor that works by inhibiting the enzymatic activity of HDAC1, HDAC2, HDAC3 (Class 1) and HDAC 6 (Class II) at nanomolar concentrations (IC50<86nM). In some cancer cells, excess amounts of the enzyme HDAC prevent the activation of genes that control normal cell activity. Based on in vitro studies, ZOLINZA is believed to decrease the activity of HDAC. Decreasing the activity of HDAC allows for the activation of genes that may help to slow or stop the growth of cancer cells. The exact mechanism of the anticancer effect of ZOLINZA has not been fully characterized.
ZOLINZA is approved in the United States for treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. As pulmonary embolism and deep vein thrombosis have been reported as adverse reactions, physicians should be alert to the signs and symptoms of these events, particularly in patients with a prior history of thromboembolic events. Treatment with ZOLINZA can cause dose-related thrombocytopenia and anemia. If platelet counts and/or hemoglobin are reduced during treatment with ZOLINZA, the dose should be modified or discontinued. Gastrointestinal disturbances, including nausea, vomiting and diarrhea, have been reported and may require the use of antiemetic and antidiarrheal medications. Fluid and electrolytes should be replaced to prevent dehydration. Pre-existing nausea, vomiting and diarrhea should be adequately controlled before beginning therapy with ZOLINZA.
Hyperglycemia has been observed in patients receiving ZOLINZA. Serum glucose should be monitored, especially in diabetic or potentially diabetic patients receiving ZOLINZA. Adjustment of diet and/or glucose therapy may be necessary. QTc prolongation has been observed. Monitor electrolytes and ECGs at baseline and periodically during treatment. Administer with caution in patients who have or may develop QTc prolongation. Hypokalemia or hypomagnesemia should be corrected prior to administration with ZOLINZA.
The most common adverse events observed in clinical trials with ZOLINZA for CTCL, regardless of causality, were fatigue (52 percent), diarrhea (52 percent), nausea (41 percent), dysgeusia (28 percent), thrombocytopenia (26 percent), anorexia (24 percent), decreased weight (21 percent) and muscle spasm (20 percent).
Commitment to oncology research
Merck is committed to all aspects of cancer care – prevention, treatment and supportive care. Through strong internal research capabilities, selective alliances and acquisitions, and enabling technologies such as the molecular profiling platform of Rosetta, Merck is looking to lead in the discovery, development and delivery of targeted anticancer therapies customized for patient subpopulations.
About Merck
Merck & Co., Inc., is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not onlydonate its medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events orotherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007 and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.
###
|
