Dalfampridine sustained-release for symptomatic improvement of walking speed in patients with multiple sclerosis.

Abstract

Dalfampridine sustained-release (SR) is a time-release formulation of 4-aminopyridine, recently approved by the Food and Drug Administration to improve walking in patients with multiple sclerosis (MS). In Phase II trials, walking speed and lower extremity muscle strength was increased in patients with MS, but the increase in walking speed did not reach statistical significance. A responder analysis revealed that approximately 35% of treated patients had a statistically significant and clinically meaningful increase in walking speed. When treated responders were compared with treated nonresponders, walking speed significantly increased in the responder group, but not in the nonresponder or placebo groups. This result was duplicated in two larger Phase III trials. The optimal dose to maximize the risk-benefit ratio was 10 mg twice daily. Higher doses were associated with a greater risk of seizure, but no further improvement in walking speed or in the proportion of responders. Dalfampridine SR is eliminated by renal clearance and undergoes only limited metabolism (<10%). It is contraindicated in patients with moderate or severe renal insufficiency and in those with a history of seizures or epileptiform activity on electroencephalography. The development of time-released 4-aminopyridine represents a major advance in symptomatic therapy for MS.