Pharmacyclics Demonstrates Potential Inhibition In Multiple Types Of Cancer
Pharmacyclics presented preclinical results demonstrating the anti-tumor activity of PCI-27483, the company's small-molecule Factor VIIa inhibitor. The data were presented during the Annual Meeting of the American Association for Cancer Research (AACR) being held this week in San Diego, CA.
Researchers reported that in animal models of human pancreatic tumors, treatment with PCI-27483 led to inhibition of tumor growth. PCI-27483 was administered twice daily at either 60 mg/kg or 90 mg/kg, resulting in 42 percent and 85 percent inhibition of tumor growth, respectively, after 15 days of treatment. Additional mechanistic studies showed that PCI-27483 blocked key tumor growth signals. Previous work has shown significant growth inhibition in lung and colorectal cancer models. Pharmacyclics anticipates filing an IND for PCI-27483 in the second half of 2008.
"These results support our IND-enabling studies for use of PCI-27483 in treatment of cancer and to protect against associated thromboembolic diseases," said David J. Loury, Ph.D., vice president of preclinical studies for Pharmacyclics. "These findings indicate that Factor VIIa inhibition is potentially a novel treatment approach for patients whose tumors depend on Factor VIIa activity for progression."
Factor VII is a blood protein involved in clotting. Many types of cancer, such as lung, breast, pancreatic, colorectal, gastric and others, express high levels of a cell surface protein known as tissue factor. After binding to tissue factor, Factor VII becomes activated and triggers a host of physiologic processes that facilitate the growth, invasion and spread of many tumors, as well as angiogenesis, or the growth of new blood vessels that supply the tumors with nutrients and oxygen. Activation of Factor VII (Factor VIIa) by tissue factor also leads to the high incidence of thrombotic complications seen in cancer patients. PCI-27483 selectively inhibits Factor VIIa when it is complexed with tissue factor.
"We're encouraged by the promising preclinical results with PCI-27483 as we broaden our portfolio of product opportunities," said Richard A. Miller, M.D., president and chief executive officer of Pharmacyclics. "We are working to move additional drug candidates forward from our diverse pipeline, including an HDAC inhibitor, now in a Phase 1 clinical trial for solid tumors, and motexafin gadolinium, which is currently in two Phase 2 trials sponsored by the National Cancer Institute."