BURROUGHS WELLCOME’s EXOSURF IS APPROVED

Executive Summary

BURROUGHS WELLCOME's EXOSURF IS APPROVED on Aug. 2 for the prophylaxis and treatment of infants at risk for respiratory distress syndrome. The synthetic lung surfactant has been available under a Treatment IND since July 1989. FDA approved the synthetic lung surfactant within a record 10 days of an approval recommendation by FDA's Pulmonary-Allergy Drugs Advisory Committee ("The Pink Sheet" July 30, p. 10) and six months after the Feb. 16 NDA submission. Exosurf has been classified a "1A" drug by FDA, designating a therapeutic advance over existing therapies, in this case, for a life-threatening disease. About 40,000 to 50,000 mostly premature infants suffer from respiratory distress syndrome (RDS). The drug is also one of a handful of new therapies approved under FDA's expedited review. Labeling for the drug states that Exosurf Neonatal for Intratracheal Suspension "is indicated for (1) prophylactic treatment of infants with birth weight less than 1350 grams who are at risk of developing RDS, (2) prophylactic treatment of infants with birth weight greater than 1350 grams who have evidence of pulmonary immaturity, and (3) rescue treatment of infants who have developed RDS." For prophylactic treatment, Exosurf is to be administered immediately after birth. In the case of rescue treatment, labeling states that "infants considered as candidates for rescue treatment with Exosurf Neonatal should be on mechanical ventilation and have a diagnosis of RDS." In its review of Exosurf, the FDA advisory committee expressed its concern that RDS be established prior to beginning treatment with Exosurf. Exosurf is supplied as a lyophilized powder in a 10 ml vial accompanied by one 10 ml vial of sterile water for injection and five endotracheal tube adapters of different diameters. Prophylactic treatment requires a single 5 ml/kg dose, while rescue treatment uses two 5 ml/kg doses administered through an endotracheal tube. Labeling informs the physician that "a videotape on dosing is available from your Burroughs Wellcome Co. representative" to demonstrate proper administration. Two adverse events associated with the administration of Exosurf are included in the warnings section. Labeling notes that "in a single study conducted in infants weighing [less than] 700 grams at birth, the incidence of pulmonary hemorrhage (10% vs 2%) was significantly increased in the Exosurf Neonatal group." Overall pulmonary hemorrhage in the clinical trials, however, was only 2% in the Exosurf group compared to 1% for placebo. In uncontrolled trials of 7,700 infants, the incidence of pulmonary hemorrhage increased to 4%. A second potential problem associated with the administration of Exosurf is mucous plugging of the endotrachael tube, which can be resolved by "suctioning of all infants prior to dosing," labeling notes. There are no contraindications to the use of Exosurf. Both Exosurf and Abbott's natural lung surfactant Survanta were recommended for approval at the July 23 meeting of the FDA advisory committee. However, Exosurf will be the first lung surfactant on the market, while Abbott awaits approval. Although both drugs have received orphan designation, differences in their chemical composition will allow both to gain orphan exclusivity for the indication. Burroughs Wellcome and Abbott are conducting clinical trials for the use of surfactant in adult respiratory distress syndrome. On July 30, Abbott announced its "Lifeline" program by which it will distribute Survanta free of cost to uninsured patients once the product is approved. The program will cover the cost of the drug, but not the cost of administration, for patients who have no private or public insurance and have family incomes of less than $40,000. The company estimates that it will donate approximately $10 mil. worth of Survanta during the first year following approval. Survanta has been available under a Treatment IND since September 1989.