OR WAIT null SECS
New molecular entity: Dalfampridine (Ampyra) was approved in January 2010, as a treatment to improve walking in patients with multiple sclerosis.
Dalfampridine 10-mg extended release tablets were approved by FDA in January 2010, as a treatment to improve walking in patients with multiple sclerosis. Dalfampridine (previously referred to as fampridine sustained-release), through its broad-spectrum potassium channel blockade, has been shown to increase nerve conduction and improve walking speed in patients with multiple sclerosis. Multiple sclerosis is a chronic and progressive disease that attacks the immune system resulting in degradation of nervous system function in the spinal cord and brain. Currently, more than 400,000 Americans are thought to suffer from multiple sclerosis. Of these, it is estimated that anywhere from 64% to 85% of patients will report having difficulty walking; and within 15 years of diagnosis, 50% of patients will require assistance walking. Dalfampridine is the first and only FDA-approved oral drug addressing walking impairment in patients with multiple sclerosis.
Efficacy. Dalfampridine's efficacy was evaluated in two phase 3 clinical trials enrolling multiple sclerosis patients. In these clinical trials, walking speed (in feet per second), the trial's primary end point, was measured as a timed 25-foot walk (T25FW). A significantly greater proportion of patients taking dalfampridine 10 mg twice daily were deemed responders (showed faster walking speeds for at least 3 visits out of a possible 4 during the double-blind period) compared with patients taking placebo (T25FW responder rate in Trial 1: 34.8% vs 8.3%; Trial 2: 42.9% vs 9.3%) in these clinical trials. The increased T25FW response rate in the dalfampridine group was seen regardless of the type of multiples sclerosis suffered. Moreover, in both trials, consistent improvements in T25FW were shown to be associated with improvements on the 12-item Multiple Sclerosis Walking Scale (MSWS; a validated patient self-assessment of ambulatory disability).
Safety. The most worrisome adverse effect of dalfampridine is seizure. The risk of seizures has been found to increase with increasing dalfampridine doses. Because of concern for this adverse event, dalfampridine is contraindicated in patients with a prior history of seizure and should be discontinued in patients in which seizure occurs. In three placebo-controlled clinical trials of dalfampridine lasting up to 14 weeks duration, 4% (15/400) of patients treated with dalfampridine had treatment emergent adverse events leading to discontinuations compared with 2% (5/238) of placebo-treated patients. The treatment emergent adverse events leading to discontinuation of at least 2 patients treated with dalfampridine and that led to discontinuation more frequently compared with placebo were headache (dalfampridine 0.5% vs placebo 0%), balance disorder (dalfampridine 0.5% vs placebo 0%), dizziness (dalfampridine 0.5% vs placebo 0%), and confusional state (dalfampridine 0.3% vs placebo 0%).