FDA PREPARING TO END LONG BAN ON THALIDOMIDE.

Byline: Sheryl Gay Stolberg The New York Times

Thalidomide, the drug whose use in the 1960s produced thousands of babies with flipperlike arms and other gross deformities, is on the verge of receiving approval from the Food and Drug Administration, nearly four decades after the agency's legendary decision to reject it for use in the United States.

Officials at the agency announced Monday that they intended to approve thalidomide for use in leprosy patients, as long as the New Jersey-based company seeking to market it could adhere to several conditions, including elaborate restrictions designed to keep the drug away from women who are or might become pregnant.

But the potential benefits of thalidomide are vast, and experts expect doctors to quickly begin prescribing it for ``off-label'' uses. In recent years, thalidomide has been experiencing a revival of sorts, and scientists are experimenting with it for maladies as diverse as AIDS, brain cancer, lupus and other autoimmune diseases. Advocates for people with these conditions have been urging the agency to make it available.

``The company has met its scientific obligation in showing that the benefits outweigh the risks'' in treating leprosy, said Dr. Murray Lumpkin, deputy director of the FDA's Center for Drug Evaluation and Research. ``The issue now is how can you manage the downsides of this drug? That is the challenge.''

Lumpkin could not say how soon the drug might be approved for use. But an official with Celgene Corp., the company seeking the approval, said he expected that Celgene would be able to satisfy the FDA's conditions, which were outlined in a letter sent to the company Friday, in a matter of weeks. The official, Bruce Williams, said the company already had produced enough of the drug to market it immediately after approval. ``When we agree on the final labeling, then we'll be ready to roll,'' he said.

News of the letter to Celgene left surviving thalidomide victims saddened, but not surprised. ``This is not a happy day,'' said Randy Warren, who was born without hips after his mother took the drug and who now leads the Thalidomide Victims Association of Canada. ``But it is certainly not a day we didn't expect. It's another stop on the journey of tears.''

Health experts said approval of the drug, especially if it was used for a variety of conditions, almost certainly would lead to the births of babies with defects seen in countries where thalidomide was marketed as a sedative in the 1960s.

``Thalidomide is now becoming a wonder drug,'' said Dr. Norman Fost, an ethicist and pediatrician at the University of Wisconsin. ``Once it is approved by the FDA there is nothing to stop doctors from prescribing it for other things. It will be crucial that there be safeguards to prevent off-label prescribing, and there is no good mechanism for doing that.''

It will now be up to the FDA and Celgene, whose stock rose 62 cents Monday on the Nasdaq, to agree on a system for distributing the drug. They will not have to start from scratch; Celgene already has proposed tight controls, based on a system used for acutane, an acne drug that has severe side effects in pregnant women. Williams, Celgene's vice president for marketing, said the restrictions would apply to all patients who take thalidomide.

Under Celgene's proposal, drugstores would be required to register to buy thalidomide, and pharmacists would not be permitted to dispense more than a month's worth of the drug. There would be no automatic refills, and all patients would be required to register in a national database before receiving the drug.

Doctors and their patients would be required to undergo extensive education, and women of childbearing age would be required to show proof that they were using contraception. Female patients also would be required to take pregnancy tests at least once a month.

If such restrictions were to be imposed, Lumpkin said in an interview earlier this month, thalidomide would become the most heavily regulated drug in the nation.

In enacting the controls, said Fost, the pediatrician, the FDA must strike a delicate balance, weighing the interests of women who need the drug against the knowledge that deformed babies will undoubtedly be born.

``The goal here is not to produce zero risk,'' he said. ``The only way to do that is not to have the drug on the market. But you can get it close to zero without limiting access to women in a way that is unreasonable.''

Warren, meanwhile, said he was bracing himself for the birth of more ``thalidomiders'' as he calls himself and the 5,000 other survivors. ``I think one baby is going to be one baby too many,'' he said. ``I dread that day more than this day.''

The FDA's announcement Monday came just two weeks after a panel of outside scientific advisers voted 8-2 to recommend that the agency approve the drug for patients with erythema nodosum leprosum, or ENL, a complication of leprosy that causes skin lesions, fever and other symptoms. At that hearing, some of the FDA's own medical experts recommended that the ban remain in effect, saying they feared that the drug would become too widely available through off-label use.

Leprosy affects about 7,000 people in the United States, 250 of whom receive thalidomide through a government ``compassionate use'' program. But tens of thousands more people with cancers and certain AIDS-related illnesses, including the severe weight-loss condition known as wasting, also might benefit from the drug.