A sustained-release formulation of the potassium channel blocker dalfampridine has been approved by the Food and Drug Administration as a treatment to improve walking in people with multiple sclerosis.
In a statement, the FDA announced that dalfampridine extended-release tablets had been approved for this indication, based on studies that found patients treated with the drug had faster walking speeds than did those treated with placebo. This is the first drug approved for this indication, according to the FDA.
Dalfampridine will be marketed as Ampyra by Acorda Therapeutics Inc. of Hawthorne, N.Y.
At a meeting in October 2009, the majority of an FDA advisory panel voted that Acorda had provided “substantial evidence” of effectiveness for this indication, although only one-third of the patients in the two pivotal trials were considered responders. Most of the panel also agreed that the drug could be considered safe for use in people with MS, but not in patients who have a history of seizures and those with severe renal insufficiency.
The recommended dose of dalfampridine is 10 mg twice a day. However, higher doses have been associated with seizures, and the drug should not be taken by patients with moderate to severe kidney disease, whose blood levels with dalfampridine approach the levels that have been associated with seizures, according to the FDA statement.
The drug has a long history of use in the United States despite never having been approved, according to background documents filed by the FDA for the advisory panel meeting. For more than 20 years, dalfampridine has been compounded in pharmacies and used off-label to improve walking in people with various neurologic conditions. However, fampridine's narrow therapeutic range makes plasma levels difficult to regulate with the immediate-release formulation, which is associated with an increased risk of seizures. The sustained formulation was developed to overcome these limitations.
In clinical trials, the most common adverse reactions in patients taking dalfampridine included urinary tract infections, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhea, indigestion, throat pain, and skin sensations including burning, tingling, and itching.
At the meeting, representatives of Acorda said that dalfampridine improves conduction in demyelinated axons.