Tecfidera: Positive Data from Three Phase 3 Studies

Biogen presented new data at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain (October 7–10), showing that Tecfidera (dimethyl fumarate) significantly reduced multiple sclerosis (MS) relapses and delayed disability progression, with effects sustained over six years of follow-up, in newly-diagnosed patients and those early in their disease course.

Data based on the DEFINE (Determination of the Efficacy and safety of oral Fumarate IN relapsing-rEmitting MS) and CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting MS) studies, both global, two-year, randomized, multi-center, double-blind, placebo-controlled, dose-comparison Phase 3 clinical trials evaluating Tecfidera in relapsing-remitting multiple sclerosis (RRMS) patients will be presented. The DEFINE study evaluated Tecfidera vs. placebo, with a primary objective to determine if Tecfidera was effective in reducing the proportion of relapsing patients at two years. The CONFIRM study investigated Tecfidera vs. placebo, with a reference comparator arm of glatiramer acetate (GA) vs. placebo. The primary objective was to determine whether Tecfidera was effective in reducing the rate of clinical relapse at two years compared to the placebo group.

An analysis of the DEFINE and CONFIRM studies shows that Tecfidera had significant effects on clinical outcomes in RRMS patients who initiated treatment early in their disease course, defined as those patients with a baseline Expanded Disability Status Scale (EDSS) score of ≤2.0 (indicating minimal to no disability). Tecfidera reduced annualized relapse rate (ARR) by 63% (P<0.0001) and reduced risk of 12-week confirmed disability progression by 40% (P=0.0066) compared to placebo.

New data also include a post-hoc analysis of the CONFIRM study, in which Tecfidera significantly reduced key inflammatory disease outcomes compared to GA. The overall hazard ratio (HR) for Tecfidera compared to GA was 0.77 (95% CI: 0.59−0.99; P=0.0446), and the overall HR for Tecfidera compared to placebo was 0.60 (95% CI: 0.46−0.79; P=0.0002).

Preliminary data was also presented from the ENDORSE study, an ongoing global, dose-blind, Phase 3 extension study to determine the long-term safety and efficacy of Tecfidera in 1,738 patients with RRMS who completed the DEFINE or CONFIRM studies. Patients will be followed for up to eight years. The primary objective of the study is to evaluate the long-term safety profile of Tecfidera.

Updated six-year data from an integrated post-hoc analysis of the DEFINE, CONFIRM and ENDORSE studies show long-term treatment with Tecfidera resulted in strong and sustained effects on relapses and disability progression in newly-diagnosed patients. Throughout six years of study (two years in DEFINE or CONFIRM followed by four years in ENDORSE), the ARR for patients who started Tecfidera treatment at the beginning of the study (n=85) remained low at 0.14 (0.10–0.19). In those patients who switched from placebo to Tecfidera, the ARR was substantially reduced from 0.26 (0.18–0.37) from the placebo period (years zero to two) to 0.10 (0.06–0.16) when Tecfidera treatment was received (years three to six), representing a 61% reduction of risk.