Tecfidera (dimethyl fumarate)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved March 2013

Specific Treatments:

relapsing multiple sclerosis

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General Information

Tecfidera (dimethyl fumarate) is an oral, small molecule immune modulator. The mechanism by which dimethyl fumarate exerts its therapeutic effect in multiple sclerosis is unknown. However, it has been postulated that dimethyl fumarate has the potential to reduce the activity and impact of inflammatory cells on the central nervous system (CNS) and induce direct cytoprotective responses in CNS cells.

Tecfidera is specifically indicated for the treatment of adults with relapsing forms of multiple sclerosis.

Tecfidera is supplied as a delayed-release capsule for oral administration. The recommended initial dose is 120 mg twice a day orally. After 7 days, the dose should be increased to the maintenance dose of 240 mg twice a day orally. Tecfidera should be swallowed whole and intact. It can be taken with or without food.

Clinical Results

FDA Approval
The FDA approval of Tecfidera was based on two studies (Studies 1 and 2) that evaluated Tecfidera taken either twice or three times a day in subjects with relapsing-remitting multiple sclerosis (RRMS).
Study One:
This 2-year, randomized, double-blind, placebo-controlled study enrolled 1,234 subjects who received Tecfidera 240 mg twice a day (BID), 240 mg three times a day (TID) or placebo for up to 2 years. The median time on study drug for all treatment arms was 96 weeks. The primary endpoint was the proportion of patients relapsed at 2 years. Additional endpoints at 2 years included the number of new or newly enlarging T2 hyperintense lesions, number of new T1 hypointense lesions, number of Gd+ lesions, annualized relapse rate (ARR), and time to confirmed disability progression. All endpoints were reached with statistical significance. The Tecfidera 240 mg three times daily dose showed no additional benefit over the twice daily dose. For the primary endpoint: the proportion of patients relapsed at 2 years was 27% in the Tecfidera 240 mg BID arm versus 46% in the placebo arm (p<0.0001).
Study Two:
This 2-year multicenter, randomized, double-blind, placebo-controlled study included an open-label comparator arm in subjects with RRMS. A total of 1,067 subjects were randomized to Tecfidera 240 mg BID, 240 mg TID or placebo for up to 2 years. The median time on study drug for all treatment arms was 96 weeks. The primary endpoint was the annualized relapse rate at 2 years. Additional endpoints at 2 years included the number of new or newly enlarging T2 hyperintense lesions, number of T1 hypointense lesions, number of Gd+ lesions, proportion of patients relapsed, and time to confirmed disability progression. Tecfidera had a statistically significant effect on the relapse and MRI endpoints. There was no statistically significant effect on disability progression. The Tecfidera 240 mg TID dose resulted in no additional benefit over the 240 mg BID dose. For the primary endpoint, annualized relapse rate at 2 years: 0.224 for the Tedfidera 240 mg BID arm and 0.401 for the placebo arm (p<0.0001).

Side Effects

Adverse events associated with the use of Tecfidera may include, but are not limited to, the following:

  • flushing
  • abdominal pain
  • diarrhea
  • nausea

Mechanism of Action

Tecfidera (dimethyl fumarate) is an oral, small molecule immune modulator. The mechanism by which dimethyl fumarate exerts its therapeutic effect in multiple sclerosis is unknown. DMF and the metabolite, monomethyl fumarate (MMF), have been shown to activate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in vitro and in vivo in animals and humans. The Nrf2 pathway is involved in the cellular response to oxidative stress. MMF has been identified as a nicotinic acid receptor agonist in vitro.

Literature References

Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT; DEFINE Study Investigators Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. New England Journal of Medicine 2012 Sep 20;367(12):1098-107

Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT; CONFIRM Study Investigators Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. New England Journal of Medicine 2012 Sep 20;367(12):1087-97

Additional Information

For additional information regarding Tecfidera or relapsing multiple sclerosis, please visit the Tecfidera web page.