Blood
VX-680 : An Aurora Kinase Inhibitor Enters an Additional Phase I Study for its Use in Hematologic Cancers
By Merck & Co, Inc and Vertex Pharmaceuticals Incorporated
Jun 20, 2005, 10:52

Merck & Co, Inc and Vertex Pharmaceuticals Incorporated announced the initiation of an additional Phase I clinical study with VX-680, a small molecule inhibitor of Aurora kinases. The two-part, open-label, dose escalation study is designed to evaluate the safety and tolerability of VX-680 when administered over a five-day treatment cycle in patients with hematologic cancers.

The study will evaluate VX-680 in patients with relapsed or refractory acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) in blast crisis. With the start of this clinical study, Merck and Vertex now have three clinical studies underway with VX-680 in cancer.

The initiation of this clinical study is supported by VX-680's activity against hematologic cancers in both in vitro and in vivo studies. VX-680 is a potent inhibitor of Aurora kinases and of Flt-3 kinase, which have been implicated in the onset and progression of human leukemias.

VX-680 has demonstrated prolonged survival and induced sustained remission in a model of human AML, and has also shown profound effects in a number of other preclinical cancer models.

"The biologic profile and preclinical studies of VX-680 indicate that this compound has the potential for treating a broad range of human leukemias by inducing apoptosis in the cells that drive disease," said Stephen H. Friend, M.D., Ph.D., executive vice president, Advanced Technology and Oncology, Merck Research Laboratories. "The clinical study announced today is designed to promote rapid clinical assessment of VX-680 in patients with a variety of leukemic and pre-leukemic disease states. In addition, access to the leukemic cells in the blood provides a unique opportunity for understanding the biologic effects and anti-cancer activity of Aurora kinase inhibition on a molecular level."

VX-680 Clinical Studies

In addition to this Phase I study in hematologic cancers announced today, Merck is presently conducting two clinical studies of VX-680 in patients with recurrent or non-responsive solid tumors, or cancers for which standard therapy does not currently exist.

Background: Aurora Kinases and the VX-680 Collaboration

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 (also known as BTAK and STK15) 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, including colon cancer, breast cancer and leukemia. Amplification of Aurora genes is associated with progression of colorectal cancer and poor prognosis in certain types of breast cancer.

In June 2004, Vertex and Merck entered into a global collaboration to develop and commercialize VX-680. Along with clinical development, Vertex and Merck are conducting a joint research program to characterize VX-680's activity across a broad range of cancer types and will seek to identify additional drug candidates targeting the Aurora kinases.

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