Impact of extended-release dalfampridine on walking ability in patients with multiple sclerosis

Abstract

Dalfampridine extended release (ER) 10 mg is an oral tablet form of the potassium (K+) channel-blocking compounded dalfampridine, also known as fampridine, and chemically 4-aminopyridine or 4-AP, which received regulatory approval in the United States for the treatment of walking in patients with multiple sclerosis (MS) in January 2010. Two pivotal Phase 3 clinical trials demonstrated significant improvements in walking in patients with the four primary forms of MS following administration of dalfampridine ER tablets 10 mg twice daily. The drug is thought to act by restoring conduction in focally demyelinated axons and by enhancing neurotransmission, thereby leading to improved neurological function. This review describes how dalfampridine represents a new pharmacotherapeutic approach to the clinical management of mobility impairment. It describes the mechanism of action and chemistry of dalfampridine ER, its pharmacokinetics, tolerability, and side effects, and the outcomes of multicenter trials showing its efficacy in improving walking speed. Clinician and patient global assessments, as well as patient self-assessment of the impact of MS on their gait disability, confirm clinically relevant benefit from the therapy. Patients tolerate the drug well and their improvement in terms of household and community ambulation, inferred from analysis of pooled data from several studies, is likely to translate into benefits in the performance of instrumental activities of daily living and a reduction in the neuropsychiatric burden of disease.

Critical Appraisal of Evidence for Improving Gait Speed in People with Multiple Sclerosis

“…Cost-effectiveness should also be considered in future research trials of dalfampridine and rehabilitation to enable comparison of the costs and benefits of each treatment approach. As Hayes 7 argues, another important priority for future research is to examine whether dalfampridine-ER can produce clinically meaningful improvements in instrumental activities of daily living and employment. Indeed, walking in the real world is far more complex than walking in the clinic or laboratory setting, and real-world ambulation typically involves the concurrent performance of cognitive tasks, such as talking (ie, dual tasking).…”

“…The pharmacokinetics of dalfampridine-ER have been examined in several clinical studies [12][13][14][15][16] and summarized in recent review articles 7,17 and will not be detailed herein. To briefly summarize the mechanism of action, dalfampridine (chemical name: 4-aminopyridine) is a potassium-channel blocker that is believed to improve maximum speed in any of the off-drug assessments).…”

“…Thus, it is not surprising that people with MS report walking as one of their priorities. 6 Dalfampridine extended-release (dalfampridine-ER), although a relatively new treatment option, is rapidly growing as a pharmacologic approach for the management of gait-related impairment in MS. 7 The efficacy of treatment with dalfampridine-ER (10-mg tablets taken twice daily) for improving gait speed in people with MS has been established in two phase 3 clinical trials. 8,9 The pooled analysis of these two trials 10 showed that individuals treated with dalfampridine-ER motor function in people with MS by increasing nerve conduction through demyelinated axons.…”

The role of exercise in modifying outcomes for people with multiple sclerosis: a randomized trial

“…Since funding was secured for this trial, there has been increasing interest in prescribing Fampyra to increase gait speed and thus an additional strata was created to avoid having an imbalance of people on Fampyra (dalfampridine;prolonged-release fampridine tablets) in one of the groups [83,84]. …”

Comparative Randomized, Single‐Dose, Two‐Way Crossover Open‐Label Study to Determine the Bioequivalence of Two Formulations of Dalfampridine Tablets

“…3,4 Nonetheless, walking disabilities are predominant in patients with MS. 5 MS affects more than 400 000 individuals in the United States and more than 2.5 million individuals worldwide, with an estimated prevalence of 90 per 100 000 population. 12 In 2008, Phase 3 of dalfampridine clinical trials was initiated, 13 and in January 2010, the molecule was granted US Food and Drug Administration approval in the Unites States as a treatment to improve walking impairments in patients with MS. 8 However, such treatment strategies do not cover the broad spectrum of MS clinical manifestations; therefore, other pharmacologic agents may be used to specifically control the complications and symptoms of MS. 9 Walking impairment is a complication of MS that leads to a varied extent of disabilities that dramati-cally affect the quality of life in patients with MS. 10 Treatments of such mobility impairments are typically limited.…”