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.
“We are particularly encouraged by the 6-Minute Walk result, as this marks the first time that data on AMPYRA's effects have been assessed on this measure.”
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,>® (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.
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.
A planned secondary outcome measure of improvement in walking, the 6-Minute Walk Test, was applied at Visit 2 in a subset of the study participants (approximately 50 randomized per treatment arm). The 10 mg dose, but not the 5 mg dose, showed a significant improvement compared to placebo (10 mg +129 ft vs. placebo +42 ft).
Changes in perceived effect of MS on walking-related activities, as measured by the self-reported 12-Item MS Walking Scale (MSWS-12), showed improvements for the 10 mg and 5 mg groups that were not significant compared to placebo.
"We believe the current study, together with the AMPYRA registration studies, continue to show that 10 mg twice daily is the appropriate, safe and effective dose. The 5mg twice daily dose of dalfampridine-ER failed to show efficacy over placebo on the primary or secondary measures. The 10 mg twice daily dose, which has consistently shown efficacy in our well-controlled clinical trials, did not meet the previously untested primary outcome measure selected for this study. We believe that this was due to increased patient variability, related to the study design. However, the 10 mg dose showed significant improvements in the 6-Minute Walk and in responder analyses of the Timed 25-Foot Walk," said Enrique Carrazana, M.D., Acorda's Chief Medical Officer. "We are particularly encouraged by the 6-Minute Walk result, as this marks the first time that data on AMPYRA's effects have been assessed on this measure."
No new safety signals were observed in this study. No seizures were reported. Two participants experienced serious adverse events in each of the 5 mg and the 10 mg treatment groups, including loss of consciousness in one patient in the 10 mg group who had discontinued dalfampridine-ER four days prior to the event. Adverse events that occurred in the combined dalfampridine-ER group at a rate of at least 2% greater than the placebo group included: urinary tract infection (8.0% vs. 5.6% placebo), nausea (7.7% vs. 3.5% placebo), dizziness (7.7% vs. 2.1% placebo), insomnia (6.3% vs. 4.2% placebo) and upper respiratory tract infection (2.8% vs. 0.7% placebo). Overall, adverse events were consistent with the U.S. Food and Drug Administration (FDA)-approved product labeling.
The study results will be provided to FDA and presented in peer-reviewed scientific forums. The Company is continuing to analyze data from the study.
AMPYRA is currently approved by the FDA as a treatment to improve walking ability in people with MS. This was demonstrated by an increase in walking speed. The only approved dosage strength of AMPYRA is 10 mg, which is taken twice daily. As specified in the product labeling, AMPYRA tablets should not be split, crushed, chewed or otherwise compromised, as doing will compromise the extended release properties of the tablet.
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