The National Institute of Allergy and Infectious Diseases andCelgene Corp. are co-sponsoring clinical trials of thalidomide fortreatment of HIV, Celgene announced on Monday.

Celgene of Warren, N.J., has exclusive rights to the use ofthalidomide for HIV and other uses under a 1992 agreementwith Rockefeller University.

Rockefeller has patents pending in the U.S. for thalidomide andother new compounds that work on tumor necrosis factor alpha(TNFa). Celgene has an exclusive license to drugs that evolvefrom Rockefeller's TNF program.

Celgene (NASDAQ:CELG) reported that preclinical workconducted in Gilla Kaplan's lab at Rockefeller has shown thatSynovir selectively inhibits the synthesis of TNFa, a cytokinebelieved to be a potent activator in HIV replication. Thecompound inhibited HIV activation in the peripheral bloodmononuclear cells of 16 of 17 patients with advanced HIV-1infection or AIDS. "It is hypothesized that by regulating theproduction of TNFa, Synovir may significantly slow theprogression of the disease," Celgene said.

The randomized, placebo-controlled, dose-escalation studieswill be conducted through NIAID's AIDS Clinical Trials Group.They will assess safety, patient tolerance to daily oral doses ofthalidomide, pharmacokinetic data, and initial data on anti-viral markers and viral burden. Men and infertile women willbe eligible for the trials.

Thalidomide made history in the late 1950s and early '60s andled to an overhaul of FDA drug regulation. The drug wasmarketed as a sedative in the late 1950s and was commonlyprescribed to pregnant women for treatment of morningsickness. While a new drug application for thalidomide waspending at FDA, the drug was found to be a teratogen; aftermany children were born with severe birth defects it waspulled from the market overseas. In response to thethalidomide disaster, Congress revised the Food, Drug &Cosmetic Act in 1962 to require that drugs be found effectiveas well as safe before gaining FDA approval. (Until that time,drugs were only required to be proven safe.)

For the past 30 years, thalidomide has been available for thetreatment of ENL, a disease condition of leprosy that Celgene'spresident, Sol Barer, said is associated with high TNF levels.Barer said FDA has obtained the drug from a Brazilian companyand provided it to the Gillis W. Long Hansen's Disease Center inCarville, La. Established in 1894 as a leper home, the centernow conducts research and provides treatment for Hansen'sdisease.

Thalidomide is Celgene's first drug to enter clinicals. Barer saidthat in the second quarter the company plans to begin Phase IItesting of Synovir for treatment of cachexia (wasting) in peoplewith AIDS, based on data Rockefeller has obtained under itsinvestigational new drug (IND) application. Last year Synovirwas designated an orphan drug for the treatment ofmycobacterial infections and Celgene has applications pendingfor orphan designation for treatment of other AIDS associateddiseases, including recurrent aphthous stomatitis.

Celgene is focused on developing drugs that modulatecytokines, particularly TNF. In addition to Synovir, it has othercompounds in preclinical development for treatment of suchautoimmune diseases as lupus, multiple sclerosis andinflammatory bowel disease. The company also supplies chiralintermediates to several pharmaceutical companies.

-- Brenda Sandburg News Editor

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