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Pharmacyclics, Inc. today announced results from a preclinical study evaluating PCI-32765, an orally available, selective inhibitor of Bruton's tyrosine kinase, or Btk, in collagen induced arthritis, an established animal model for rheumatoid arthritis (RA)
SUNNYVALE, CA, USA |.June 9, 2008 | Pharmacyclics, Inc. (Nasdaq: PCYC) today announced results from a preclinical study evaluating PCI-32765, an orally available, selective inhibitor of Bruton's tyrosine kinase, or Btk, in collagen induced arthritis, an established animal model for rheumatoid arthritis (RA). The data were presented during the Federation of Clinical Immunology Societies (FOCIS) meeting being held this week in Boston, MA.
Researchers examined the impact of treatment with PCI-32765 on mouse models of rheumatoid arthritis at disease onset, and with established active disease. Treatment prevented further joint swelling when animals were dosed at early stages of disease. In animals with advanced disease, treatment with PCI-32765 reduced inflammation and induced regression of disease with approximately 50% reduction in histopathologic score after only five days of dosing. Treatment with PCI-32765 was found to inhibit mast cell function and to prevent allergic reaction, with passive cutaneous analphylaxis inhibited by more than 95%. In other studies, human B-cell activation was shown to be selectively inhibited by drug treatment in vitro. PCI-32765 also inhibited the proliferation of, and induced apoptosis in, multiple B-cell lymphoma cell lines in vitro, suggesting that Btk inhibition could be a novel drug target in lymphoma.
"This study suggests that treatment with PCI-32765 causes a potent combined blockade of both B-cell and mast cell activation," said Joseph J. Buggy, Ph.D., vice president of research for Pharmacyclics. "This dual blockade may account for the preclinical efficacy seen in established arthritis models and holds promise for potential use in humans with advanced RA and other immune mediated diseases. The inhibition of B-cell function and proliferation in the various models, including lymphomas, forms the basis for our phase 1 clinical trial, which is anticipated to begin in the fourth quarter of calendar 2008."
Btk is a critical enzyme involved in B-cell activation and mast cell function, and inhibition of its function may be useful in the treatment of immune mediated diseases. Mast cells play a key role in the inflammatory process and are implicated in the pathology associated with the autoimmune disorders, such as RA and in allergy. Recently, mast cells have been found to play an important role in tumor growth and angiogenesis. B-cells are a type of white blood cell that normally play an important role in the body's immune response. However, when B-cells are overactive, the immune system produces inflammatory cells and antibodies that begin to attack the body's own tissue, leading to autoimmune disorders. Most lymphomas are caused by uncontrolled growth of B-cells where activation of the B-cell receptor and Btk signaling are thought to play important roles.
About Pharmacyclics
Pharmacyclics is a pharmaceutical company developing innovative products to treat cancer and other serious diseases. The company is leveraging its small-molecule drug development expertise to build a pipeline in oncology and other diseases based on a wide range of targets, pathways and mechanisms. More information about the company, its technology, and products can be found at http://www.pharmacyclics.com. Pharmacyclics(R) and the "pentadentate" logo(R) are registered trademarks of Pharmacyclics, Inc.
SOURCE: Pharmacyclics, Inc. |
