Drug Product Name:

TECFIDERA Rx

TECFIDERA

Active Ingredient(s):
Dimethyl fumarate 120mg, 240mg; delayed-release caps.

Company
Biogen Idec, Inc.

Indication(s):

Treatment of patients with relapsing forms of multiple sclerosis.

Pharmacology:

Dimethyl fumarate (DMF) and its 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.

The mechanism by which dimethyl fumarate exerts its therapeutic effect in multiple sclerosis is unknown.

Clinical Trials:

The efficacy and safety of Tecfidera were demonstrated in two studies that evaluated Tecfidera taken either twice daily or three times daily. The starting dose for Tecfidera was 120mg twice or three times daily for the first 7 days, followed by an increase to 240mg twice or three times daily.

Study 1 was a 2-year randomized, double-blind, placebo-controlled study. 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. Patients were randomized to receive Tecfidera 240mg twice daily, Tecfidera 240mg three times daily, or placebo for up to 2 years. Results showed that Tecfidera had a statistically significant effect on all the endpoints and the Tecfidera 240mg three times daily dose showed no additional benefit over the twice daily dose. On the primary endpoint, the Tecfidera 240mg twice daily treatment group demonstrated a lower proportion of patients with relapses vs. placebo (27% vs. 46%; P<0.0001) with a 49% relative risk reduction.

Study 2 was a 2-year multicenter, randomized, double-blind, placebo-controlled study that also included an open-label comparator arm. The primary endpoint was the ARR 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. Patients were randomized to receive Tecfidera 240mg twice daily, Tecfidera 240mg three times daily, an open-label comparator, or placebo for up to 2 years. Results showed that Tecfidera had a statistically significant effect on the relapse and MRI endpoints. There was no statistically significant effect on disability progression. The Tecfidera 240mg three times daily dose did not result in additional benefit over the twice daily dose. On the primary endpoint, the ARR was lower in the Tecfidera 240mg twice daily treatment group vs. placebo (0.224 vs. 0.401; P<0.0001) with a 44% relative reduction. See full labeling for detailed results.

Legal Classification:

Rx

Adults:

Swallow whole. Take with or without food. Initially 120mg twice daily for 7 days, then increase to 240mg twice daily.

Children:

Not established.

Warnings/Precautions:

Obtain CBCs (within 6 months) prior to initiation to identify pre-existing lymphopenia; test annually, and as clinically indicated. Serious infection; consider withholding until resolved. Pre-existing low lymphocyte counts (not studied). Administration with food may reduce incidence of flushing. Pregnancy (Category C). Nursing mothers.

Adverse Reaction(s)

Flushing, abdominal pain, diarrhea, nausea, vomiting, pruritus, rash; lymphopenia.

How Supplied:

Starter Pack (30-day)—1 (120mg × 14 + 240mg × 46); Delayed-rel caps 120mg—14; 240mg—60

LAST UPDATED:

5/31/2013

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