Abstract Details

Title Safety and Efficacy of 5mg and 10mg Dalfampridine Extended Release Tablets in Patients with Multiple Sclerosis: First Results from a Double-Blind, Placebo-Controlled Trial

Topic MS and Related Diseases

Presentation(s) P04 - (-)

Poster/Presentation
Number 096

Objective

Background BACKGROUND: Dalfampridine-ER 10mg tablets, twice daily, are approved to improve walking in patients with MS.

Design/Methods DESIGN/METHODS: Subjects were randomized to double-blind treatment with twice daily dalfampridine-ER 5mg (n=144), 10mg (n=143), or placebo (n=143) for 4 weeks. Primary efficacy was a previously untested endpoint: change from baseline in walking speed (WS) using the Timed 25-Foot Walk test 3-4 hours after the last dose of dalfampridine-ER at Week 4. Drug effects were compared using ANOVA.

Results RESULTS: Characteristics were balanced among treatment groups; subjects were primarily women (70%), mean age 52.6 years, with baseline WS 2.75 ft/sec. WS changes from baseline were 0.36, 0.42, and 0.48 ft/sec for placebo, dalfampridine-ER 5mg, and 10mg, respectively. Changes with dalfampridine-ER were not significant relative to placebo. Post-hoc analysis of WS change between pre-treatment and on-treatment periods showed that relative to placebo, only dalfampridine-ER 10mg resulted in a significantly greater increase in WS (mean±SE) with treatment (0.443±0.042ft/sec versus 0.303±0.039ft/sec; P=0.014) and percent change in WS (19.9±2.2% versus 12.8±1.8%; P=0.010). Six serious AEs occurred: breast abscess/cellulitis and urosepsis in the dalfampridine-ER 5mg group; ovarian adenoma, vertigo, and a loss of consciousness (4 days after drug discontinuation) in the dalfampridine-ER 10mg group. No seizures were observed. The most common AEs were consistent with previous studies.

Conclusions CONCLUSIONS: Dalfampridine-ER 5mg twice daily failed to demonstrate efficacy. While the 10mg dose also failed to show efficacy using a previously untested endpoint, significant effects were observed in a post hoc analysis that was more consistent with clinical studies and prescribing information.

Authors/Disclosures
Ben W. Thrower, MD (Shepherd Center) PRESENTER	Dr. Thrower has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Thrower has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Thrower has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon. Dr. Thrower has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS.
Robert A. Yapundich, MD, FAAN (Frye Care Neurology)	No disclosure on file
E M. Bebin, MD, FAAN (UAB Epilepsy Center)	Dr. Bebin has received personal compensation for serving as an employee of Springworks Therapeutics. Dr. Bebin has received personal compensation for serving as an employee of Apertura Gene Therapy. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springworks Therapeutics. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Apertura. The institution of Dr. Bebin has received research support from NINDS. The institution of Dr. Bebin has received research support from FDA Orphan Drug Program.
Angela Applebee, MD (St Peter'S MS Center)	Dr. Applebee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Applebee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Applebee has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Applebee has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Applebee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Horizon. Dr. Applebee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb.
George J. Hutton, MD, FAAN (Baylor College of Medicine)	Dr. Hutton has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Autoimmunity Biologic Solutions, Inc.. The institution of Dr. Hutton has received research support from Biogen. The institution of Dr. Hutton has received research support from Genentech. The institution of Dr. Hutton has received research support from Genzyme.
	No disclosure on file
Herbert Henney, PharmD (Acorda Therapeutics, Inc.)	No disclosure on file
Andrew Blight, PhD (Acorda Therapeutics, Inc)	No disclosure on file
Enrique J. Carrazana, MD	No disclosure on file

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