Acorda Therapeutics, Inc. (Nasdaq: ACOR) today announced top line results from a post-marketing commitment study evaluating a 5mg dose of dalfampridine-ER to improve walking in people with multiple sclerosis (MS). The study failed to confirm efficacy of the 5mg dose.
The study randomized 430 participants across three treatment arms: placebo, 5 mg or the currently marketed dose of 10 mg of dalfampridine-ER, twice daily. Baseline characteristics were measured at a single visit after randomization, following a qualifying screening visit. Study drug was then given for 4 weeks. Participants returned after 2 weeks on study drug for interim measurements (Visit 2), and again at 4 weeks (Visit 3).
The primary outcome was the change in walking speed (feet/second) on the Timed 25-Foot Walk (T25FW) test at Visit 3, measured at the time of peak plasma drug concentration, versus baseline.
Improvements in the primary outcome for the 5 mg dose (0.423 ft/sec, p=0.457) and the 10 mg dose (0.478 ft/sec, p=0.107) at Visit 3 were not statistically significant compared to placebo (0.363 ft/sec). The AMPYRA
(dalfampridine) Extended Release Tablets, 10 mg registration studies used a consistent response analysis to allow for the variability in MS-related symptoms, including walking ability. The design of the current study required a single endpoint analysis that had not been used previously in the AMPYRA development program. In a post-hoc analysis, T25FW data were analyzed with methods similar to those used in the pivotal studies, combining all measures prior to treatment as the baseline and all measures on treatment as the on-drug value. The average change from baseline in walking speed was significantly greater for the 10 mg group compared to placebo (0.443 vs. 0.303 ft/sec, p=0.014) but not for the 5 mg group (0.366 vs. 0.303 ft/sec, p=0.292).
In addition, using a responder definition of average improvement in walking speed of at least 20% from baseline, similar to an analysis presented in the AMPYRA prescribing information, the 10 mg group showed significantly more responders than the placebo group (44% vs. 27%, p=0.004). The 5 mg group did not show a significant increase in response over placebo (32% vs. 27%, p=0.366).