FDA approves Tecfidera for multiple sclerosis

The Food and Drug Administration has approved a new, twice-daily oral medication, dimethyl fumarate, for relapsing-remitting multiple sclerosis.

The drug, to be marketed as Tecfidera, is thought to defend the brain against oxidative stress, and experimental evidence has suggested that it may also act both as an anti-inflammatory and as a neuroprotective agent.

Tecfidera joins a host of already approved medications for MS. Two forms of interferon beta-1a (Avonex and Rebif) and two forms of interferon beta-1b (Betaseron and Extavia) have been approved for the relapsing-remitting form, as has glatiramer acetate (Copaxone), fingolimod (Gilenya), and teriflunomide (Aubagio). Natalizumab (Tysabri) is approved for relapsing-remitting MS, but with restrictions. Mitoxantrone (Novantrone) is approved for secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS, according to the National MS Society. Dalfampridine (Ampyra) is approved to improve walking in individuals with MS.

"No drug provides a cure for multiple sclerosis, so it is important to have a variety of treatment options available for patients," said Dr. Russell Katz, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

According to the FDA, MS is among the most common causes of neurologic disability in young adults and occurs more frequently in women than men. Some 400,000 Americans are living with the condition, and the relapsing-remitting form is the most common. That is characterized by episodes of worsening function, followed by recovery periods. But recovery periods become less complete over time, leading to progressive decline in function and increased disability.

Dimethyl fumarate was approved based on results from two phase III trials that enrolled more than 2,600 patients: DEFINE and CONFIRM. DEFINE data were originally reported at the Fourth Cooperative Meeting on Multiple Sclerosis in 2011 and the CONFIRM data were reported at the Joint Congress of ECTRIMS/ACTRIMS in 2012.

According to Biogen Idec, which makes dimethyl fumarate, relapses were reduced by 49% in patients taking the drug in the DEFINE trial, and disability by 38%. Relapses declined by 34% in the CONFIRM study. In both trials, dimethyl fumarate significantly reduced lesions in the brain, when compared with placebo.

"In clinical trials, patients treated with dimethyl fumarate had less disease activity when compared to patients on placebo – whether they were in the early stages of MS or had more established disease," said Dr. Robert Fox, medical director of the Mellen Center for Multiple Sclerosis at Cleveland Clinic, in a Biogen statement. Dr. Fox was the lead investigator of the CONFIRM study, and is a paid adviser for Biogen Idec for projects not related to dimethyl fumarate. "This drug provides physicians with an important additional treatment option for their patients across the MS spectrum," Dr. Fox said.

The FDA said that dimethyl fumarate decreases lymphocyte counts, but that there was no evidence of an increase in infections in patients taking the drug in trials. The agency recommends monitoring lymphocyte counts before starting therapy, and annually thereafter. Flushing and gastrointestinal problems were the most common adverse reactions.

Biogen said the drug would be available in a matter of days. The recommended starting dose is 120 mg twice a day orally. After a week, the recommended dose increases to 240 mg twice daily.

aault@frontlinemedcom.com

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