MERCK, VERTEX START STUDY OF AURORA KINASE INHIBITOR

Merck and Vertex Pharmaceuticals have 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 study 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.

Merck will conduct the international Phase II 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 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 Ph+ 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 study 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.

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.

In 2004 Vertex entered into a global collaboration with Merck to develop and commercialize MK-0457 (VX-680) and other follow-on Aurora kinase inhibitors.