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| |  Sustained Release Fampridine Provides Improvement in Walking Speed for Subset of Patients With MS Over Long Term: Presented at ECTRIMS By Chris Berrie DÜSSELDORF, Germany -- September 14, 2009 -- Extended use of fampridine sustained release (SR) to over 2 years appears to provide significant sustained improvements in the walking speed of known responders with multiple sclerosis (MS), without causing any new safety issues, researchers reported here at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Lead investigator Andrew Goodman, MD, Department of Neurology, University of Rochester, Rochester, New York, presented an interim analysis of this open-label extension study here on September 10 on behalf of the MS-F203/203EXT Study Group. In the initial randomised, double-blind, controlled, phase 3 trial, patients were randomised to placebo (n = 72) or fampridine-SR 10 mg (n = 224) twice daily. The primary endpoint for the original study was satisfied by a significant increase in timed-walk responder rate over placebo for fampridine-SR treatment (8.3% vs 34.8%, P < .001). The eligibility criteria for the open-label extension with fampridine-SR 10 mg twice daily were as follows: definite MS; aged 18 to 70 years; and a timed 25-foot walk (T25FW) of 8 to 45 seconds duration at initial study screening. Of the 283 patients eligible to continue on to the open-label extension, 269 patients enrolled. Open-label subjects had the following baseline demographics: mean age of 52.1 years; 77.7% female; and a mean Expanded Disability Status Scale (EDSS) score of 5.76. The range of MS disease types included: secondary progressive (52.8%), relapsing-remitting (23.6%), primary-progressive (14.9%), and progressive-relapsing (3.7%). An efficacy analysis was based on the proportion of extension timed walk (ETW) responders, whereby walking speed at the majority of the first 4 open-label visits had to be faster than the fastest speed during any of the preceding 7 off-drug visits. “This is a fairly rigourous and tough criterion to meet,” stressed Dr. Goodman, “because not only does it have to beat, as a threshold, the fastest time from 7 off-drug visits, but it also has to be sustained over the course of 1 year.” For this interim analysis, fampridine-SR treatment is currently at 2.6 years, with a mean treatment time of 1.9 years. Of 195 patients who remain active in the study at this point, 55 are ETW responders, and 140 are ETW nonresponders. Responders demonstrate just under a 30% mean improvement in walking speed over baseline, while nonresponders demonstrate a decline in T25FW of 8%. The mean Subject and Clinical Global Impression (SGI/CGI) scores of the ETW responders were significantly improved over those of the nonresponders (SGI: 5.3 vs 4.7; P < .001; CGI: 3.2 vs 3.7; P < .001), as was their change in EDSS score (-0.06 vs 0.35; P = .018). Overall, adverse events (AEs) were experienced by 97.4% of patients, with 23.4% experiencing serious AEs; there were 4 deaths (1.5%). The most frequent treatment-emergent serious AE was MS relapse (4.1%), although there were incidences of cellulitis (1.9%) and convulsion (1.1%). Dr. Goodman briefly focused on these 3 patients with convulsion, because, as he said, “Historically, seizure/convulsion has been a concern with 4-amino pyridine because of the known pharmacology and prior studies that showed a dose-related increased risk of seizure.” He noted, however, that the seizure-related events over all extension studies with fampridine-SR 10 mg twice daily to date show an incidence of 0.41 per 100 patient-years, which is comparable to a previously reported expected incidence of first seizure in an MS population of 0.35 per 100 patient-years. Dr. Goodman felt, therefore, that this extension study demonstrates no new safety signals, and suggests that there is a subset of these MS patients who have experienced sustained improvements in walking speeds for over 2 years. He noted, however, that without a placebo control, it is impossible to make any definitive assessment. Funding for this study was provided by Acorda Therapeutics Inc. [Presentation title: Interim Analysis of an Open-Label Extension Study of Sustained Release Fampridine in Patients With Multiple Sclerosis. Abstract O43]
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