Dalfampridine is used to improve walking in patients with multiple sclerosis (MS). Dalfampridine has been designated an orphan drug by the US Food and Drug Administration (FDA) for relief of symptoms of multiple sclerosis. In clinical studies in MS patients who received the recommended dalfampridine dosage, walking improvement was demonstrated by increased walking speed in a timed 25-foot walk (T25FW). In those who responded to dalfampridine (approximately 35-43%), walking speed increased 25-29% and was maintained until the drug was discontinued.
Although only a portion of MS patients appear to respond to dalfampridine treatment with increased walking speed, improved walking during such treatment has been demonstrated in all MS disease types (relapsing remitting, primary progressive, secondary progressive, progressive relapsing). It is not clear what magnitude of improvement in walking speed results in improved walking ability or quality of life. Although consistent improvements in walking speed were shown to be associated with improvements on a patient self-assessment of ambulatory disability (12-item Multiple Sclerosis Walking Scale; MSWS-12), the average MSWS-12 score during dalfampridine treatment was not different than that reported with placebo. Improvement in walking speed reported with dalfampridine is independent of concomitant therapy with biologic response modifiers used for the management of MS (interferon, glatiramer acetate, natalizumab).
Data are insufficient regarding the safety and efficacy of dalfampridine for the management of other MS symptoms (e.g., motor function assessed using manual muscle testing, visual function, cognitive function, fatigue).
FDA labeling for use of dalfampridine for improved walking in MS patients is based on results of 2 randomized, double-blind, placebo-controlled phase 3 studies involving 540 adults with MS who had a mean disease duration of approximately 13 years, a mean Kurtzke Expanded Disability Status Scale (EDSS) score of 6, and had the ability to walk 25 feet in 8-45 seconds at baseline. The primary measure of efficacy in both studies was walking speed (feet per second) as measured by the T25FW, using a responder analysis that assessed consistency of improvement during treatment. Treatment responders were defined as those who had walking speeds for at least 3 visits (out of a possible 4 visits) during the double-blind treatment period that were faster than the maximum speed achieved during any of the 5 visits outside the treatment period.
One study (study 1, MS-F203) involved 301 adults with MS who were randomized to receive 14 weeks of dalfampridine extended-release tablets (10 mg twice daily) or placebo. Most patients (67%) were receiving stable therapy with a biologic response modifier used for the management of MS (interferon, glatiramer acetate). Patients with a history of seizures or evidence of epileptiform activity on EEG screening, those with onset of an MS exacerbation within the past 60 days, and pregnant and breast-feeding women were excluded. Approximately 35% of patients receiving dalfampridine were responders compared with 8% of those receiving placebo. In responders, the increase in walking speed was maintained throughout the treatment period and the increase from baseline averaged 25.2% (0.5 feet per second) in those who received dalfampridine compared with 4.7% (0.1 feet per second) in those who received placebo.
The other study (study 2, MS-F204) involved 239 adults with MS who were randomized to receive 9 weeks of dalfampridine extended-release tablets (10 mg twice daily) or placebo. In addition to the same inclusion and exclusion criteria used in study 1, study 2 excluded patients with severe renal impairment. Most patients (59%) were receiving stable therapy with a biologic response modifier used for the management of MS (interferon, glatiramer acetate). Approximately 43% of patients receiving dalfampridine were responders compared with 9% of those receiving placebo. The mean increase in walking speed ranged from 21-27% in those who responded to dalfampridine and 7-9% in those who responded to placebo.