ELANPRES NEEDS TIME/COURSE, ALDOMET COMPARISON DATA FOR APPROVAL -- FDA CMTE.

Executive Summary

Elan's once daily methyldopa (Elanpres) is not ready for approval due to questions about the drug's sustained action over 24 hours, FDA's Cardio-Renal Drug Advisory Committee recommended unanimously at its Sept. 29 meeting. Panel member Franz Messerli, MD, Oschner Medical Institutions, said that at 12 hours, Elanpres showed "clear antihypertensive activity," but he was "not so sure" about the drug's antihypertensive effect "after 24 hours." As a prelude to an approval decision, the panel suggested that the company do time/course of action studies to determine the drug effect on blood pressure over a full 24-hour period. Explaining the panel's rationale for requesting time/course of action data, committee Chairman Jeffrey Borer, MD, Cornell Medical Center, noted: "If there were a wide fluctuation between say 12 and 24 hours, one might be giving a certain dose to achieve a certain effect at 24 hours and achieve a great deal more than that in terms of blood pressure reduction earlier on, perhaps more blood pressure reduction than is clinically appropriate or necessary." In addition to time/course of action data, the committee recommended that Elan submit a study versus Aldomet in a comparative dosage regimen. The panel also suggested that the company might choose to submit data for a b.i.d. regimen. Elan's NDA for Elanpres was based primarily on a single, multi-center study in 102 patients comparing the drug in four different dosage regimens -- 350 mg, 700 mg, 1050 mg and 1400 mg -- with placebo. Efficacy data was presented in terms of mean systolic/diastolic blood pressure drop per treatment group at 12 hours and 24 hours over an eight-week period, which included a two week washout and crossover design. Elan filed for a 700 mg dosage form because the study showed an efficacy plateau after that dose.