To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Thalomid (Thalidomide), TNF-alpha Modulators Show Promise in Inflammatory Bowel Disease URL: http://www.pslgroup.com/dg/1D3686.htm Doctor's Guide May 25, 2000
WARREN, NJ -- May 25, 2000 -- Celgene Corporation announced that researchers presented both preclinical and clinical data on the use of Thalomid® (thalidomide) and Celgene's proprietary class of Tumor Necrosis Factor Alpha (TNF-alpha) modulators, the SelCIDs™, or Selective Cytokine Inhibitory Drugs, respectively, in inflammatory bowel diseases at the annual meeting of the American Gastroenterological Association (AGA), also known as Digestive Disease Week (DDW). Both studies were conducted in cooperation between the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center in Los Angeles and Celgene Corporation. Researchers reported that three members of Celgene's proprietary class of compounds, the SelCIDs, were more potent inhibitors of TNF-alpha and interferon gamma in lamina propria mononuclear cells than thalidomide. Chronic inflammation of lamina propria mononuclear cells, which reside in the intestinal lining, is linked to chronic inflammatory diseases. Inhibition of TNF-? has been shown to be of clinical benefit in the treatment of Crohn's disease. In this study, the second generation SelCID compounds were even more active than the lead SelCID that is currently being tested in a pilot phase II Crohn's disease trial. "This study reinforces the potential utility of these compounds in the treatment of inflammatory diseases such as Crohn's disease," said George Muller, Ph.D., a co-author of the study and Director of Medicinal Chemistry at Celgene. "The specificity of these SelCIDs for inhibiting production of these cytokines supports clinical research initiatives in conditions like inflammatory bowel disease and rheumatoid arthritis." Celgene has previously reported that the SelCID most advanced in clinical trials had been well tolerated in initial human safety trials. Drs. John L. Prehn and Stephan Targan of Cedars-Sinai Medical Center and George W. Muller, Hon-Wah Man and David I. Stirling of Celgene authored the study. Researchers also reported interim results of an open-label pilot study of the use of thalidomide in seven adult men with moderate to severe ulcerative colitis (UC) who were resistant or intolerant to high-dose 5-aminosalicylate (5-ASA), steroids or immunomodulatory therapy. Five patients received 100 mg of thalidomide at night and two patients received 50 mg. Within four weeks, three patients responded to treatment with a median decrease in the modified Truelove and Witts disease activity scale by seven points. The median score of non-responders was unchanged. On a quality of life scale, inflammatory bowel disease quotient (IBDQ), responders reported a median improvement of thirty seven points. One initial responder discontinued treatment at the eighth week due to decreased libido. By the twelfth week of the study, the responders achieved remission and discontinued steroids. At this time their IBDQ scores had risen to 73 and 85 points. Adverse events included sedation, decreased libido, and dry skin. Drs. Lori Y. Kam, Eric A. Vasiliauskas, Maria T. Abreu, Philip V. Hassard, and Stefan R. Targan of Cedars-Sinai Medical Center and Jerome Zeldis of Celgene authored the study. "As a result of this and previous studies, Celgene will investigate whether patients with ulcerative colitis can have their disease controlled by thalidomide and the SelCIDs and IMiDs while being weaned off of corticosteroids." said Jerome Zeldis, M.D., Ph.D., Vice President for Medical Affairs at Celgene. As many as one million Americans may suffer from inflammatory bowel disease with prevalence evenly split between Crohn's disease and ulcerative colitis. Researchers have reported that Crohn's disease tends to run in families, and that the disease is most common in North America, Europe and Scandinavia, with a greater incidence of the disease in urban and northern environments. 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). The major adverse reactions known to be associated with thalidomide include peripheral neuropathy, a common potentially severe side effect that may be irreversible; drowsiness/somnolence; dizziness/orthostatic hypertension; neutropenia; and increased HIV-viral load. Physicians should consult full prescribing information about these and other adverse reactions prior to initiating treatment with Thalomid (thalidomide). Celgene has filed more than 20 patents worldwide related to SelCIDs, of which eight U.S. patents have already been issued. The Company has been granted patents covering different structural classes of SelCID compounds. It is the Company's plan to broaden studies in various disease models, initiate clinical trials of the SelCIDs in inflammatory diseases and continue to strengthen the intellectual property for this class of drugs. IMiDs, or Immunomodulatory Drugs, the Company's other new class of compounds, are a group of novel, patented, structural analogues developed and synthesized based on the biological activity and structure of thalidomide. IMiDs, which are described as the next generation of thalidomide, have been designed to enhance the ability of the drug to inhibit chronic overproduction of the inflammatory protein, (TNF-alpha), with fewer side effects. These new compounds are also being tested for their effectiveness as anti-angiogenic agents. The two lead clinical candidates were recently reported to be safe and well tolerated in a phase I, single escalating dose study in healthy male volunteers. Celgene plans to initiate phase I/II IMiD studies in oncology patients this year. Celgene Corporation, headquartered in Warren, New Jersey, is an independent biopharmaceutical company engaged in the discovery, development and commercialization of small molecule drugs for cancer and immunological diseases. Related Links: Thalomid (thalidomide) and Celgene Corporation. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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