Preparing for Thalidomide's Comeback

Thalidomide is on the verge of being introduced-with great care-into the U.S. marketplace. The news provokes polarized reactions: disbelief that such a potent teratogen could be made available after the lessons of almost 40 years ago, and impatience for a drug that can lead to exceptional improvements in some rare debilitating immune diseases.

In early September, an advisory committee to the U.S. Food and Drug Administration (FDA) recommended that the FDA approve marketing of thalidomide for erythema nodosum leprosum, an inflammatory manifestation of leprosy that results in painful cutaneous lesions on the arms, legs, and face. The committee also strongly recommended limiting distribution of thalidomide, with stringent safety measures put in place to avoid birth defects and other side effects.

The renewed interest in thalidomide comes from studies showing a complete response in 90% of patients with erythema nodosum leprosum who used thalidomide, according to Janet Woodcock, MD, chief of the FDA's Center for Drug Evaluation and Research. The drug is also under investigation to determine its effectiveness against graft-versus-host disease, the AIDS wasting syndrome, some solid tumors, certain serious primary dermatologic conditions, tuberculosis, aphthous ulcers, and macular degeneration. Woodcock said that evidence is most compelling for the drug's effect on aphthous ulcers in patients with HIV infection (N Engl J Med. 1997; 335:1487-93) and with Behcet disease. She considers the data on the AIDS wasting syndrome “promising” but preliminary.

The committee's recommendation was preceded by a year of intensive debate and planning because of the drug's potentially severe side effects. Even one dose of thalidomide, when taken during the early stages of pregnancy, can cause fetal deformities. The …