The US Food and Drug Administration (FDA) announced today approval for dalfampridine (Ampyra, Elan/Acorda Therapeutics) extended-release tablets to improve walking in patients with multiple sclerosis (MS).
The drug, a potassium channel blocker, was shown in clinical trials to improve walking speeds vs placebo. It is the first drug approved for this use, an FDA statement notes; currently approved MS drugs are indicated to decrease relapse rates or in some cases to prevent accumulation of disability.
“Trouble with walking is one of the most debilitating problems people with MS face,” Russell Katz, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, said in a statement.
The drug was previously known as fampridine sustained release with the proposed brand name Amaya, but is now called dalfampridine (Ampyra). The change was made to avoid potential confusion with other marketed products, a spokesperson for the FDA confirmed. It will be manufactured under licenses from Elan of Dublin, Ireland, and distributed by Acorda Therapeutics Inc of Hawthorne, New York.
Given at doses greater than the recommended 10 mg twice a day, dalfampridine can cause seizures, the statement adds. The most common adverse events reported in clinical trials were urinary tract infection, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhea, indigestion, throat pain, and burning, tingling, or itching of skin.
Dalfampridine, the statement adds, "should not be used in patients with moderate or severe kidney disease. In these patients, blood levels with the drug approach those associated with the occurrence of seizures."
A press release from Acorda notes that dalfampridine demonstrated efficacy in all 4 major types of MS, including relapsing-remitting, secondary progressive, progressive relapsing, and primary progressive, and can be used alone or in combination with immunomodulatory drugs.
Substantial Evidence of Effectiveness
In October 2009, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee voted to support approval of the New Drug Application for the drug, as reported by Medscape Neurology at that time.
The committee voted 12 to 1 that clinical data on the 10-mg twice-daily dose demonstrated substantial evidence of effectiveness as a treatment to improve walking in MS patients and 10 to 2, with 1 abstention, that the improvement is clinically meaningful and the drug can be safe for use.
Because of concerns about adverse effects, particularly seizures, and what they viewed as a narrow therapeutic window, the committee also recommended by a vote of 12 to 1 that the company be required to study doses lower than 10 mg but also voted not to require these studies before approval.
A risk evaluation and mitigation strategy program providing healthcare professional and patient education for the appropriate use of dalfampridine was proposed by Acorda, the company noted in a statement at the time of the FDA meeting. The FDA approved the drug with a REMS, a press release from Acorda notes, comprising a medication guide and a communication plan aimed at informing patients about the serious risks, including seizures, associated with higher than recommended doses and informing them of the name change.
The FDA granted dalfampridine orphan drug status, providing them 7 years of market exclusivity for the drug. Acorda expects dalfampridine to be available in the United States in March 2010, the company statement adds, "distributed exclusively through a network of specialty pharmacies and coordinated by Ampyra Patient Support Services."
"Walking impairment affects a large majority of people with MS, and we are very pleased that the FDA has approved a new treatment that addresses this aspect of the disease," John Richert, MD, executive vice president for Research & Clinical Programs at the National Multiple Sclerosis Society, is quoted as saying in the Acorda release. "Continuing to advance clinical research and expand the range of therapeutic options for people with MS, including treatments for the most debilitating symptoms and challenges associated with the disease, is critical to helping people with MS."
