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Merck and Vertex Announce Start of Pivotal Phase 2 Clinical Trial for Investigational Aurora Kinase Inhibitor MK-0457 (VX-680) in Patients with Treatment-Resistant Forms of Advanced Leukemias
Whitehouse Station, NJ and Cambridge, MA, December 21, 2006 -- Merck & Co., Inc. (NYSE: MRK) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the start of an international clinical trial of MK-0457 (also known as VX-680), an investigational small molecule inhibitor of Aurora, FLT-3, JAK-2 and BCR-ABL kinases. The trial will be conducted in patients with treatment resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL) containing the T315I BCR-ABL mutation. In connection with the start of dosing in the trial, which is designed to support registration of MK-0457 in the United States and other countries, Vertex earned a $25 million milestone payment from Merck.
"This pivotal trial based on a population prospectively defined by a genetic marker will hopefully represent a new paradigm for development of drugs targeting specific cancer patient populations," said Stephen H. Friend, M.D., Ph.D., Executive Vice President and Franchise Head, Oncology and Neuroscience, Merck Research Laboratories. "MK-0457 is the first compound to show clinical activity in patients with certain treatment-resistant forms of blood cancers. Based on encouraging Phase 1 results reported recently at the American Society of Hematology meeting, we are moving forward with this international Phase 2 clinical trial in these patients."
Clinical Trial Design
Merck will conduct the international Phase 2 clinical trial of MK-0457 at various sites in the United States, the European Union, and several other countries, including Israel. The trial is expected to enroll approximately 270 adult patients with advanced CML and ALL leukemias harboring the T315I BCR-ABL mutation. Patients in the study will be enrolled in one of four cohorts: patients with accelerated phase CML, patients with blast phase CML, patients with chronic phase CML and patients with Philadelphia chromosome-positive ALL with the T315I mutation. In the trial, MK-0457 will be given as a five-day intravenous infusion every two to three weeks to evaluate both safety and efficacy. Merck may seek marketing approval for MK-0457 based on the data generated in this trial. The trial has been designed to support registration of MK-0457 in one or more cancer indications for which there is currently little or no effective treatment.
The trial is now open for patient recruitment. If interested in more information about the trial, please visit www.clinicaltrials.gov or call 1-888-577-8839. The ClinicalTrials.gov identifier for this trial is NCT00405054.
Aurora Kinases and Cancer
Cancer cells typically contain mutations in a number of genes, which ultimately result in uncontrolled cell growth and tumor metastasis. As enzymes specific for and essential to cell growth and division, Aurora kinases hold the potential to be important control points for slowing the growth and spread of tumors. Aurora kinases are a family of serine-threonine kinases that are believed to play multiple roles in the development and progression of cancer, by acting as regulators of cell proliferation, by transforming normal cells into cancer cells and by down-regulating p53, one of the body's natural tumor suppressors. Aurora kinases are known to be over-expressed in many tumor types.
Discovery of MK-0457 (VX-680)
MK-0457 was discovered by scientists at Vertex's Oxford, U.K. research site as part of a broad research effort targeting the kinase gene family. Vertex researchers published the three-dimensional atomic crystal structure of Aurora-A kinase in 2002, a key scientific advance that enabled the design and optimization of multiple classes of small molecule Aurora kinase inhibitors. MK-0457 advanced to preclinical development in 2002, following evaluation of the compound's activity in tumor cell lines and in animal models of tumor growth. In studies published in early 2004, Vertex demonstrated that MK-0457 induced tumor regression in xenograft models of human pancreatic and colon cancer. In addition, studies conducted by Vertex showed that MK-0457 prolonged survival and induced sustained remission in an oncogene-driven model of human acute myelocytic leukemia (AML).
In June 2004, Vertex entered into a global collaboration with Merck to develop and commercialize MK-0457 (VX-680) and other follow-on Aurora kinase inhibitors. As part of the collaboration, Vertex and Merck conducted a joint research program to characterize MK-0457's (VX-680) activity across a broad range of cancer types and identified additional drug candidates targeting the Aurora kinases.
About Merck Oncology
Merck Oncology focuses on 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 Oncology is looking to lead in the discovery, development and delivery of targeted anticancer therapies customized for patient subpopulations. Merck Oncology conducts research at sites in Boston, Seattle, West Point, Japan and Italy.
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 only donate Merck 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.
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, inflammation, autoimmune diseases, cancer, pain and bacterial infection. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline. Vertex's press releases are available at www.vrtx.com.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
Merck 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, or otherwise. 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 cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.
Vertex forward-looking statement
This press release may contain forward-looking statements, including statements that (i) Merck will conduct an international clinical trial of MK-0457; (ii) this clinical trial may provide a new paradigm for development of drugs targeting specific cancer patient populations; (iii) the trial will enroll 270 patients; (iv) data obtained in this trial may support an application by Merck for marketing approval for MK-0457; and (v) Aurora kinases hold the potential to be important control points for slowing the spread and growth of tumors. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause the actual results of studies to vary materially. Those risks and uncertainties include, among other things, the risk that observed outcomes in earlier clinical investigations of small numbers of patients will not be reflected in this clinical trial involving larger numbers of patients, that expectations for regulatory authority support based on possible clinical trial outcomes will not be realized, either because the outcomes are not as expected or because the regulatory authority support does not materialize, that unexpected and adverse outcomes occur in other ongoing clinical and nonclinical studies, that the expected potential benefits in modulating Aurora kinase activity are not realized or are accompanied by unacceptable toxicities, and other risks listed under Risk Factors in Vertex's Form 10-K filed with the Securities and Exchange Commission on March 16, 2006. Vertex disclaims any obligation to update the information contained in this press release as new data become available.
Lynne H. Brum, VP, Strategic Communications (617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Lora Pike, Manager, Investor Relations, (617) 444-6755
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