The FDA has cleared the way for Celgene Corporation(NASDAQ:CELG) to begin Phase II trials of its drug Synovir(thalidomide) in the treatment of cachexia in AIDS patients. Cachexia,or wasting, is weight loss and emaciation that often accompanies AIDSand cancer.Although thalidomide is best known as the drug that causedabnormalities in babies _ pregnant women took it for morningsickness during the 1960s _ Celgene is developing it as a treatment forAIDS and associated conditions.Celgene plans to begin the cachexia trials within the next three monthsat The Rockefeller University and Thomas Jefferson University inPhiladelphia, Pa. The trials will be randomized, double-blinded,placebo-controlled studies with weight gain as the clinical endpoint. Arange of viral and immunological markers will be evaluated in order toassess Synovir's impact on viral replication and immune-systemfunction.According to Celgene, thalidomide has been shown to lower theproduction of tumor necrosis factor alpha (TNFa) to basal levelswithout causing general immunosuppression.TNFa is believed topromote weight loss.Warren, N.J.-based Celgene is sponsoring the cachexia trials on itsown. However, in February this year the company signed an agreementwith the National Institute of Allergy and Infectious Diseases (NIAID)to cosponsor clinical trials of thalidomide for the treatment of HIV.NIAID will sponsor these trials through the AIDS clinical trial group.According to Sol Barer, Celgene's president and chief executiveofficer, the protocols for these trials are being finalized and Phase Itrials are slated to begin in the third quarter of 1994. Preclinicalresearch is currently being conducted at Rockefeller by associateprofessor Gilla Kaplan. According to Celgene, studies demonstrate thatthalidomide selectively inhibits the synthesis of TNFa, which isbelieved to be a potent activator of HIV replication.Waksal said Celgene is also looking at new chemical entities that havekey structural features of thalidomide. He said these compounds, forwhich Celgene has filed composition of matter patents, are still in thein vitro stages of testing. However, they might have application todiseases in which TNFa has been implicated, such as rheumatoidarthritis, inflammatory bowel disease, and multiple sclerosis.Waksal said Celegene may seek to supplement its IND for the cachexiatrials with additional clinical protocols related to other disease statesassociated with AIDS. The company already has been granted orphandrug status for the use of thalidomide to treat mycobacterial infections.n

-- Philippa Maister

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