Evaluating dalfampridine for the treatment of relapsing-remitting multiple sclerosis: does it add to the treatment armamentarium?

ABSTRACT

Introduction: Multiple sclerosis (MS) is a demyelinating disease, causing axonal damage and disability. Dalfampridine (DAL) is an extended-release formulation of 4-aminopyridine (4AP) and broad-spectrum voltage-dependent potassium channel blocker that is reported to improve motor, visual and cognitive functions. Furthermore, it is presently the only approved drug for walking impairment in MS.

Areas covered: Herein, the authors evaluate DAL as a relapsing-remitting MS treatment, reporting and commenting on all aspects of the drug including its chemistry, safety, pharmacokinetics, and cost-effectiveness. A bibliographic search was performed on PubMed using the terms ‘dalfampridine OR fampridine OR 4-aminopyridine’.

Expert opinion: Evidence from post-marketing studies suggests that DAL, consistent with the effects of 4AP, may not only improve walking speed, but also arm function, fatigue, mood and cognition through restored nerve conduction in central nervous system demyelinated areas. Long-term safety data confirm that the approved dose of 10 mg twice daily is generally well tolerated. However, despite the reported efficacy, the extent of the benefits is limited in real life activities, although significant improvements have been demonstrated in the clinical setting. Patients often complain of side effects (such as cramps and painful paraesthesia) or lack of efficacy. Also, its considerably higher pricing in comparison to 4AP represents an important limitation.

KEYWORDS:

• ambulation
• 4-aminopyridine
• cognition
• cost-effectiveness
• dalfampridine
• fatigue
• multiple sclerosis

Article highlights

• In multiple sclerosis (MS) demyelination causes impairment of central conduction.

• Dalfampridine (DAL), a voltage-dependent potassium channel blocker, in a extended release formulation, improves action potential conduction across demyelinated CNS axons.

• Efficacy of DAL on motor tasks has been demonstrated in pivotal trials.

• The less explored efficacy on fatigue, fatigability, vision, mood and cognition has an impact on quality of life of responders and renders the molecule of interest also in less impaired persons with relapsing-remitting MS.

• Less than 50% pf patients show an adequate response to DAL.

• The use of DAL is hindered by the inability to identify responders before treatment and a pricing not proportioned to efficacy.

Declaration of interest

A Lugaresi has served on the advisory boards of Bayer Healthcare, Biogen, Merck Serono, Novartis, Roche, Sanofi-Genzyme and Teva Pharmaceuticals. She has also received congress, travel, and accommodation expense support and fees for speaking from Bayer Healthcare, Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Teva Pharmaceuticals and the Fondazione Italiana Sclerosi Multipla (FISM). Her institutions also research grant support from Bayer Healthcare, Biogen, Novartis, Merck & Com Sanofi-Genzyme, Teva Pharmaceuticals and from FISM. M Foschi, furthermore, has received travel grants from Roche, Biogen, and Sanofi-Genzyme. He is also involved in clinical trials sponsored by Biogen, Roche, and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This manuscript was not funded.