More MS news articles for July 1999

Celgene Thalidomide Analogs Exert Potent
Highly Specific Immune System Responses
Reports Journal of Immunology Clinical Trial of Lead Compound
First of New Category of Anti-inflammatory Compounds
Expected to Begin Later this Year

Wednesday July 7, 7:30 am Eastern Time
Company Press Release
SOURCE: Celgene Corporation
WARREN, N.J., July 7 /PRNewswire/ -- Derivatives of thalidomide developed by Celgene Corporation exert distinct and highly specific immunotherapeutic responses that may benefit a broad range of inflammatory and immunological diseases, according to a study published in the July 1 issue of the Journal of Immunology. The study, coauthored by scientists at Celgene and The Rockefeller University, is the first to identify the immunotherapeutic activities of the new compounds, known as Immunomodulating Drugs(TM) (IMiDs).

Celgene also announced that the company had selected an IMiD(TM) compound for evaluation in initial (Phase I) clinical trials later this year. Certain IMiDs(TM), a novel class of small molecule pharmaceuticals, are being evaluated to determine if the compounds afford the same or improved immunotherapeutic effects as thalidomide but with a greatly reduced toxicity profile.

"The Journal of Immunology report identifies the distinctive and varied immunotherapeutic effects afforded by six IMiDs(TM), all of which had been proven to be potent inhibitors of tumor necrosis factor- alpha (TNF-alpha)," said David Stirling, Ph.D., coauthor and Chief Scientific Officer of Celgene. Excessive levels of TNF-alpha, a pro- inflammatory cytokine (protein), have been linked to the onset of several major inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, congestive heart failure and other conditions.

"The report greatly advances our understanding of the biological activity of these new drugs, and lays the groundwork for further preclinical and clinical evaluations," said Stirling. Previously published reports had documented the IMiDs'(TM) improved safety profile in animal models, as well as TNF-alpha inhibitory potency up to 10,000 times greater than the parent compound. The IMiDs(TM) studied were found to inhibit "proinflammatory" cytokines: interleukin-1beta, interleukin-6, and interleukin-12. They also enhanced production of an antiinflammatory cytokine, IL-10, as well as IL-2 and interferon-gamma.

"The IMiDs(TM) were also found to costimulate activity of T cells at a level 100 to 1000 times that of thalidomide," Stirling said. A second group of TNF-alpha inhibitors described in the study had previously been shown to inhibit phosphodiesterase-4 (PDE-4), an enzyme shown to influence overproduction of TNF-alpha.

"The IMiDs(TM) more closely resemble thalidomide than the PDE-4 compounds, the latter being essentially a new class of TNF-alpha inhibitors," said Dr. Stirling. "The IMiDs(TM) may have potential for treating conditions where there is a deficiency in T cell activity, such as viral diseases, including HIV-related diseases; or for enhancing potential IL-12 mediated antitumor activities "

"The findings of the Journal of Immunology study provide a strong foundation for aggressive development of selected IMiD(TM) compounds," said Sol Barer, Ph.D., President and COO of Celgene. "The varied targets of the two groups of compounds add substantial diversity to our immunotherapeutic pipeline, helping reduce investment risk and increasing our opportunities for medical and commercial success." The Journal of Immunology paper, entitled "Differential Cytokine Modulation and T Cell Activation by Two Distinct Classes of Thalidomide Analogues That are Potent Inhibitors of TNF-alpha," appeared in the July 1 issue, pages 380-386.

Celgene Corporation, headquartered in Warren, NJ, is engaged in the development of pharmaceuticals and agrochemicals. This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward- looking statements. These factors include actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as 10K, 10Q, and 8K reports.

SOURCE: Celgene Corporation