Feb 26, 2009
Positive Results Published of First of Two Phase 3 Clinical Trials of Fampridine-SR
Walking speed improved significantly in a phase 3 clinical trial of 301 people with all types of MS taking oral Fampridine-SR (Acorda Therapeutics, Inc.), a drug designed to provide symptomatic relief by compensating for lost nerve conduction. Fampridine-SR is a sustained-release formula of 4-aminopyridine, which temporarily enhances nerve signaling by blocking tiny pores, or potassium channels, on the surface of nerve fibers. A paper describing the study, by Dr. Andrew Goodman (University of Rochester) and colleagues, is published in the February 28, 2009 issue of The Lancet (2009 373;732-738).
Results from a later, second Phase 3 study, announced in 2008, confirmed Fampridine’s benefits reported here. In early February 2009, Acorda announced that it had applied to the FDA for marketing approval of Fampridine for multiple sclerosis.
Background: Problems with gait (difficulty in walking) are among the most common mobility limitations experienced by people with MS. Fampridine-SR is a sustained-release formula of 4-aminopyridine, which blocks tiny pores, or potassium channels, on the surface of nerve fibers. This blocking ability may improve the conduction of nerve signals in nerve fibers whose insulating myelin coating has been damaged by MS. The first studies of this potassium-blocking approach in people with MS were supported by the National MS Society.
The Study: A total of 301 people with all types of MS participated at 33 sites in the U.S. and Canada. Participants were randomly divided such that 224 were on active treatment and 72 were on inactive placebo over 14 weeks. Participants were permitted to remain on other medications during the trial, establishing the potential of the drug as a symptomatic management strategy that could be used along with their regular medications and disease-modifying therapies.
Results: Thirty-five percent of those on active therapy, versus only 8 percent of the placebo group, experienced significant improvements in walking speed. The walking speed for those who responded to therapy improved an average of 25.2% (in the timed 25-foot walk), compared to only 4.7 percent in the placebo group, and the improvement was maintained over the 14 weeks of therapy. Improvement was also noted in the “MS Walking Scale 12,” a measure designed to assess how meaningful the improvement was for individuals; in this study, those who responded to the drug reported feeling less disabled in daily activities requiring mobility.
Other positive outcomes included increased leg strength in those on active treatment, even in some individuals whose walking speed did not improve.
Common adverse events (side effects) experienced more often by those on active treatment included back pain, dizziness, insomnia, fatigue, nausea and balance disorder. Serious adverse events that led to discontinuation of the drug included one case of anxiety and one seizure in a person who developed sepsis from a urinary tract infection. There were no deaths during the treatment phase of the study, but one person died five weeks after the last treatment visit of heart disease, which was deemed by investigators to be unrelated to the therapy.
Results from a later, second phase 3 study, announced in 2008, confirmed the benefits seen in this trial. The company announced that it had applied to the FDA for marketing approval of Fampridine in early February 2009.
Comment: “The phase 3 results on Fampridine suggest that this drug has the potential to temporarily restore function and make a real difference to some people’s quality of life,” said John Richert, MD, Executive Vice President of Research & Clinical Programs for the National MS Society. “If the FDA agrees that Fampridine is safe and effective, it would bring a welcome symptomatic therapy that has potential utility for a large number of people with different types of MS.”
As the authors noted in the paper, “We could not identify any factor that predisposes patients with multiple sclerosis to respond to fampridine on a particular measure.” Further study and clinical practice may help determine the extent to which the drug may impact other functions not measured in the clinical trials, and provide hints as to which patients are most likely to respond.