The Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) in March recommended granting a marketing authorization for Tecfidera (dimethyl fumarate) as a first-line oral treatment for adults with relapsing-remitting multiple sclerosis (RRMS), Biogen Idec reported. The agency cited a favorable benefit-to-risk balance for Tecfidera in its decision. The CHMP recommendation must now be reviewed by the European Commission (EC). A US Food and Drug Administration decision on the marketing application for Tecfidera is expected this spring.
Dimethyl fumarate is an investigational compound for the treatment of relapsing-remitting MS that has experimentally demonstrated activation of the Nrf-2 pathway, which protects against inflammation and oxidative stress.
The CHMP recommendation is based on data from a large clinical development program that included two global Phase III studies—DEFINE and CONFIRM—as well as an ongoing extension study in which some patients have been followed for more than four years. The trials involved more than 2,600 RRMS patients. In DEFINE, Tecfidera was administered twice-daily. There was a significant 49 percent (p<0.0001) reduction in the proportion of patients who relapsed, and a 53 percent (p<0.0001) reduction in the annualized relapse rate (ARR). The 12-week confirmed disability progression, as measured by the Expanded Disability Status Scale (EDSS), was reduced by 38 percent (p=0.0050) compared to placebo at two years.
In CONFIRM, twice-daily Tecfidera significantly reduced ARR by 44 percent (p<0.0001), and the proportion of patients who relapsed was reduced by 34 percent (p<0.0001) compared to placebo at two years. A 21 percent reduction in 12-week confirmed disability progression in CONFIRM was not statistically significant. In both studies, MRI evidence showed that treatment with Tecfidera significantly reduced lesions in the brain compared to placebo.
“Clinical studies demonstrated Tecfidera was an effective therapy with a favorable safety profile for people with relapsing- remitting MS,” said Professor Gavin Giovannoni, Chair of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, in a statement. “This, combined with its interesting suggested mechanism of action, should position Tecfidera as a first-line therapy choice.”
The most common side effects associated with Tecfidera in clinical trials were flushing and gastrointestinal (GI) events (i.e., diarrhea, nausea, and abdominal pain). Other side effects include a decrease in mean lymphocyte counts during the first year of treatment. There was no increased risk of malignancy or serious infections associated with Tecfidera treatment, and no opportunistic infections were observed.
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