Executive Summary

FISONS PNEUMOPENT PCP-FREE SURVIVAL evidenced during a 24-week period in one arm of a three-arm study presented by R. Murphy, MD, Northwestern University Medical School, at the Interscience Conference on Antimicrobial Agents and Chemotherapy Sept. 20 in Houston. Aerosolized pentamidine was administered every other week via Fisons' FISONeb nebulizer at doses of 5 mg, 60 mg, and 120 mg in 175 patients with a prior episode of Pneumocystis carinii pneumonia. "Estimates for 24-week PCP-free survival were 100% in the 60 mg group, 90% in the 120 mg group, and 79% in the 5 mg group," Murphy reported. There was a statistical difference between the 5 mg and 60 mg groups; however, there was no statistical difference between the 60 mg and 120 mg groups, Murphy said. Fisons filed an NDA for Pneumopent in April and requested Treatment IND status for the drug in late March. The company met with FDA in early June to discuss the results from the new U.S. multicenter study and the status of the drug vis-a-vis Lyphomed's version of aerosolized pentamidine, NebuPent. Based on its first approval, the Lyphomed product appears to have won seven years of exclusivity as an orphan drug approval. NebuPent has been available under a Treatment IND since February and was approved by FDA in June. Adverse reactions in the Pneumopent study included mild to moderate coughing, wheezing and bronchospasm. Lyphomed's approved labeling notes similar side effects for its version during clinical trials: cough (38%) and broncospasm (15%). Four deaths occurred during the Fisons' study, although none were related to PCP or the drug. However, in another Northwestern University study of Pneumopent in 16 patients who had at least two prior episodes of PCP, one fatality was attributed to the treatment. "We did have one death, probably related to the administration of pentamidine," Murphy noted. The patient, Murphy said, developed "acute pancreatitis and died within 48 hours of massive pancreatitis." Lyphomed's approved labeling mentions the possibility of pancreatitis. The labeling states: "Cases of acute pancreatitis have been reported in patients receiving aerosolized pentamidine," and recommends discontinuing the drug when symptoms develop. Thirty-eight patients from the first study are continuing with treatment, Murphy said. To date, six patients have had breakthrough PCP and three deaths have occurred unrelated to the drug. Among the patients on Pneumopent for a longer term, the intensity of side effects seemed to increase, Murphy noted. "There was a tendency -- but I can't say anything statistically -- that there may be a little more coughing associated ]with aerosolized pentamidine[ as patients were on the treatment for a longer period of time," he said.