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
Goodman, A.D.; Bethoux, F.; Brown, T.R.; Schapiro, R.T.; Cohen, R.; Marinucci, L.N.; Henney, H.R.; Blight, A.R.; Agius, M.; Arnason, B.G.W.; Bethoux, F.A.; Bever, C.T.; Bowen, J.D.; Brown, T.R.; Dietrich, D.W.; Edwards, K.; Freedman, M.S.; Freedman, M.; Kachuck, N.J.; Kaufman, M.D.; Keilson, M.; Khan, O.; Krupp, L.B.; Leist, T.P.; Lindsey, J.W.; Lublin, F.D.; Mass, M.K.; Mattson, D.; McGowan, D.; Naismith, R.; O'Connell, C.; Oger, J.J.; Panitch, H.; Picone, M.A.; Rammohan, K.W.; Schapiro, R
Multiple Sclerosis 21(10): 1322-1331
ISSN/ISBN: 1477-0970 PMID: 25583832 DOI: 10.1177/1352458514563591
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). Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). 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. 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. 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.