First Data For Roche's Nepicastat In CHF

Roche's dopamine beta-hydroxylase inhibitor nepicastat (formerlyRS-25560-197) has shown early activity in the treatment of patients with heart failure, according to data from the first clinical trial in this setting reported at the American Heart Association meeting.

Nepicastat is designed to interfere with the neurohormonal activation seen in patients with CHF, and blocks the enzyme responsible for converting dopamine into noradrenaline. Noradrenaline levels are elevated in patients with CHF, and the raised level correlates closely with increased mortality, and the rationale is that the decrease in alpha and beta adrenergic stimulation afforded with nepicastat may improve outcomes in these patients.

Claude Benedict of the University of Texas in Houston presented data from 31 patients who were randomized to receive either placebo or 40mg, 80mg or 120mg nepicastat for 10 days. All the patients were on ACE inhibitors, and many were also taking digoxin, diuretics, warfarin and/or aspirin. As expected, there was a dose-dependent decrease in plasma noradrenaline levels with nepicastat, as well as a dose-dependent increase in dopamine levels. The drug appeared to have no effect on blood pressure or heart rate. There were also early indications that the drug increased urinary volume and sodium excretion.