Dalfampridine Extended Release

Abstract

Dalfampridine extended release (ER) is an orally administered formulation of dalfampridine (fampridine, 4-aminopyridine), a potassium channel antagonist indicated for the improvement in walking ability in patients with multiple sclerosis (MS). Oral dalfampridine ER improved walking ability in patients with MS in three randomized, double-blind trials of up to 15 weeks' duration. In a phase II trial, percentage improvements in walking speed on the Timed 25-Foot Walk (T25FW) test (primary endpoint) were not significant versus baseline or placebo during treatment with dalfampridine ER 10, 15 or 20 mg twice daily. However, according to a post hoc analysis, response rates were significantly higher with dalfampridine ER than placebo, with a consistent mean improvement in walking speed of 25-29% seen in the pooled results from dalfampridine ER responders during the double-blind treatment period. In two phase III trials, the proportion of timed walk responders (primary endpoint) was significantly greater with dalfampridine ER 10 mg twice daily than with placebo, with improvements in walking speed of approximately 25% seen during dalfampridine ER treatment amongst timed walk responders. Interim results of noncomparative extensions of the two phase III trials showed that consistent improvements in walking speed were sustained above baseline for up to 2.5 years of dalfampridine ER treatment. Oral dalfampridine ER 10 mg twice daily was generally well tolerated in patients with MS, according to the results of the three randomized, double-blind, placebo-controlled trials.