Publication in Clinical Cancer Research Reports Thalidomide and IMiDs Inhibit COX-2
Warren, NJ (November 20, 2001) — Celgene Corporation (NASDAQ: CELG) and the Joan and Sanford I. Weill Medical College of Cornell University announced today that data from an in vitro study determined that thalidomide and IMiDs (Immunomodulatory Drugs) inhibited COX-2 (Cyclooxygenase-2). Based on these data, which were published in the November 2001 issue of Clinical Cancer Research, Celgene and Weill Cornell have expanded their research partnership to an extensive three-year collaboration to evaluate the molecular mechanism by which thalidomide and IMiDs regulate COX-2 expression.
"The knowledge of how thalidomide and IMiDs modulate COX-2 will help us select the appropriate clinical indications for our current drug candidates," said David I. Stirling, Ph.D., Chief Scientific Officer of Celgene Corporation. "In addition, understanding the mechanism of action will allow us to design novel drugs targeted at cancer and inflammation."
COX-2 is an enzyme that is induced by numerous cytokines, growth factors, and tumor promoters, including lipopolysaccharide (LPS). It is known to play an important role in promoting inflammation and angiogenesis while inhibiting immune response and apoptosis. In addition to its role in inflammation, recent studies suggest that COX-2 may be pivotal in the maintenance of tumor viability, growth and metastasis. An editorial titled "Thalidomide, COX-2, and Angiogenesis: Potential for Therapy," also published in November issue of Clinical Cancer Research, reviewed evidence of the link between COX-2 and development of cancer.
In the study, conducted at Weill Cornell by Andrew J. Dannenberg, M.D. and colleagues, a macrophage cell line was treated with either LPS or LPS and thalidomide. Treatment with LPS caused an increase in the amount of COX-2; however, treatment with thalidomide caused a dose-dependent suppression of this effect. IMiDs also inhibited LPS-mediated induction of COX-2.
"These data provide new insights into the antiangiogenic and anti-inflammatory properties of thalidomide and the IMiDs," said Dr. Dannenberg, Director of Cancer Prevention, New York Presbyterian Hospital — Weill Cornell Campus. "Based on these findings and their implications, over the next three years we will further elucidate the mechanism of action by which thalidomide and the IMiDs inhibit COX-2."
The three-year research collaboration between Celgene and Cornell University will evaluate how thalidomide and IMiDs decrease the stability of COX-2 mRNA and determine if the compounds decrease TNF-alpha mRNA by a similar mechanism. An additional goal of the partnership is to identify the molecular targets that cause the reduction of COX-2 levels.
Celgene Corporation, located in Warren, New Jersey, is an independent biopharmaceutical company engaged primarily in the discovery, development and commercialization of orally administered, small molecule drugs for the treatment of cancer and inflammatory diseases through gene regulation. Please visit the Company's website at www.celgene.com for more information.
Weill Medical College of Cornell University (www.med.cornell.edu), founded in 1898, has long ranked among the leading medical schools in the U.S. From the beginning, the Medical College has followed an educational philosophy that combines a strong basic foundation in the medical sciences with extensive and early clinical training in patient care. Under Weill Cornell's innovative Strategic Plan for Research, its physicians and scientists are engaged in both basic and clinical research in the cutting-edge areas of genetics and gene therapy, neuroscience, structural biology, vascular biology, AIDS, cancer and psychiatry, among other fields. Together with Memorial Sloan-Kettering Cancer Center and The Rockefeller University, its close neighbors and affiliates on York Avenue, Weill Cornell forms one of the great biomedical complexes in both the nation and the world.
Safety Notice
Thalidomide is contraindicated in pregnant women and women capable of becoming pregnant. Even a single capsule taken by a pregnant woman can cause severe birth defects or death to an unborn baby. To minimize this risk, only prescribers and pharmacies registered with the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.®) distribution program may prescribe or dispense THALOMID® (thalidomide). Other adverse drug reactions known to be associated with thalidomide therapy include: peripheral neuropathy, a common, potentially severe side effect that may be irreversible; drowsiness/somnolence; dizziness/orthostatic hypotension; neutropenia; hypersensitivity reactions; and increased HIV-viral load. Physicians should consult full prescribing information about these and other adverse reactions prior to initiating treatment with THALOMID®.
THALOMID® (thalidomide), manufactured by Celgene Corporation, received U.S. Food and Drug Administration (FDA) clearance on July 16, 1998 for the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and as maintenance therapy for prevention and suppression of cutaneous manifestation recurrences. THALOMID® is not indicated as monotherapy for ENL treatment in the presence of moderate to severe neuritis.
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