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Clinical Trial
. 2015 Sep;21(10):1322-31.
doi: 10.1177/1352458514563591. Epub 2015 Jan 12.

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

Andrew D Goodman  1 , Francois Bethoux  2 , Theodore R Brown  3 , Randall T Schapiro  4 , Ron Cohen  5 , Lawrence N Marinucci  5 , Herbert R Henney 3rd  5 , Andrew R Blight  6 ; MS-F203, MS-F204, and Extension Study Investigators
Collaborators, Affiliations
Clinical Trial

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

Andrew D Goodman et al. Mult Scler. 2015 Sep.

Abstract

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS).

Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT).

Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW.

Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders.

Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders.

Keywords: Clinical trial; Timed 25-Foot Walk; dalfampridine; efficacy; long-term effects; multiple sclerosis; safety; sustained release; tolerability; walking speed.

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Conflict of interest statement

Conflict of interest: Goodman has received consultancy fees from Acorda Therapeutics, Biogen Idec, EMD Serono, Genzyme, GW Pharma, Mylan, Novartis, Teva and Vaccinex; and has received research support from Acorda Therapeutics, Avanir, Biogen Idec, EMD Serono, Genzyme, Novartis, Ono, Roche, Sun Pharma and Teva. Bethoux has received research support from the National MS Society, the Consortium of MS Centers, Innovative Neurotronics, Merz Pharmaceuticals, Medtronic, and Acorda Therapeutics; has served on the speakers’ bureaus of Allergan and Acorda Therapeutics; and has received consultancy fees from or served on the advisory board for Acorda Therapeutics, Merz Pharmaceuticals, GW Pharmaceuticals and Concert Pharmaceuticals. Brown has received consultancy fees from Acorda Therapeutics, Bayer, Biogen, Genzyme, Pfizer and Teva; has received honoraria from Acorda Therapeutics, Biogen, Genzyme, Pfizer and Teva; and has received research funding/grants from Acorda Therapeutics, Biogen, Galen Pharmaceuticals, Lilly and Teva. Schapiro has received consultancy fees from Acorda Therapeutics and EMD Serono; and has received research funding from EMD Serono, Bayer, Acorda Therapeutics and Teva Neuroscience. Authors Cohen, Marinucci, and Blight are employees and stockholders of Acorda Therapeutics. Henney was an employee and stockholder of Acorda Therapeutics at the time these studies were conducted.

Figures

Figure 1.
Figure 1.
Patient disposition in long-term extension studies of MS-F203 (MS-F203EXT) and MS-F204 (MS-F204EXT) participants. MS: multiple sclerosis; T25FW: Timed 25-Foot Walk.
Figure 2.
Figure 2.
Percent change from baseline in walking speed at each scheduled visit in the double-blind phase and open-label extension, by treatment allocation and dalfampridine-ER responder status in the parent study. (a) Study MS-F203EXT; (b) study MS-F204EXT. Time 0 represents the ‘Screening visit’ of the parent study; after which the double-blind phases lasted 21 weeks and 14 weeks in the two parent studies, respectively. The off-treatment periods after 14 and 21 weeks in (a) and (b), respectively, reflect the safety follow-up to the parent trials, prior to initiation of the long-term extensions. DNR: dalfampridine-ER non-responder; DR: dalfampridine-ER responder; ER: extended release; EXT: extension study; MS: multiple sclerosis; PBO: placebo.
Figure 3.
Figure 3.
Percent change from baseline in walking speed at each scheduled visit, among patients with continuous participation at approximately 2 years, by treatment allocation and dalfampridine-ER responder status in the parent study. (a) Study MS-F203EXT and (b) study MS-F204EXT. Time 0 is the ‘Screening visit’ of the parent study; the double-blind phases lasted 21 weeks and 14 weeks in these two parent studies, respectively. DNR: dalfampridine-ER non-responder; DR: dalfampridine-ER responder; ER: extended release; EXT: extension study; MS: multiple sclerosis; PBO: placebo
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