SUMMIT, N.J. - The FDA has approved Thalomid (thalidomide) in combination with Decadron (dexamethasone) for the treatment of newly diagnosed multiple myeloma.
SUMMIT, N.J., May 30 - The FDA has approved Thalomid (thalidomide) in combination with Decadron (dexamethasone) for the treatment of newly diagnosed multiple myeloma.
Celgene, which markets Thalomid, said the FDA granted accelerated approval on the basis of response rates. There are no controlled trials that demonstrated a clinical benefit, such as improvement in survival.
One recent trial found that the drug did not increase survival, while a second study reported a survival benefit for older patients, but noted that a number of serious side effects.
The use of Thalomid in multiple myeloma results in an increased risk of venous thromboembolic events, such as deep venous thrombosis and pulmonary embolus. This risk increases significantly when Thalomid is used in combination with standard chemotherapeutic agents including Decadron. In one controlled trial, the rate of venous thromboembolic events was 22.5% in patients receiving Thalomid/Decadron compared with 4.9% in patients receiving Decadron alone (P = 0.002).
The most frequently reported adverse events were constipation (55%), sensory neuropathy (54%), confusion (28%), hypocalcemia (72%), edema (57%), dyspnea (42%), thrombosis/embolism (23%), and rash/desquamation (30%), the company said.
Thalomid should never be used by women who are pregnant or who could become pregnant because even a single dose is associated with severe birth defects. Because Thalomid is present in the semen of male patients, men receiving thalidomide must always use a latex condom during sexual contact with women of childbearing potential even if he has undergone a successful vasectomy.
Thalomid, which is approved for treatment of erythema nodosum leprosum, a severe and debilitating condition associated with leprosy, can only be marketed under a special restricted distribution program. The program is called the "System for Thalidomide Education and Prescribing Safety (S.T.E.P.S)." Under this program, only registered prescribers and pharmacists may dispense the drug. In addition, patients must be advised of, agree to, and comply with the requirements of S.T.E.P.S.
The accelerated approval granted by the FDA is historically interesting since thalidomide, which was initially marketed as a tranquilizer, is the drug that is largely responsible for the FDA approval process as we know it. In 1962, thalidomide, which had been licensed in Europe, was linked to serious birth defects and the drug was banned worldwide.
The drug was never licensed in the United States because Francis Kelsey, M.D., the FDA official who was charged with reviewing the new drug application for thalidomide had reservations about the pharmacologic tests done on the drug. In the wake of the "thalidomide baby" headlines, Dr. Kelsey was hailed as a hero and President Kennedy awarded her the Distinguished Federal Civil Service Award.
Congress, meanwhile, interpreted the thalidomide story as a warning about the need to get tougher on pharmaceuticals. Senator Estes Kefauver (D-Tenn.) led the charge to pass a new Food, Drug and Cosmetic Law that expanded the FDA authority to include not only drug safety but also drug efficacy, a change that sowed the seeds of the current drug-approval process.