In a post hoc subgroup analysis of newly diagnosed patients,
TECFIDERA Had Clinical Benefits on Relapse and Disability Progression Measures¹

Study Design and Methodology

• The integrated analysis of DEFINE and CONFIRM was pre-specified prior to the unblinding of CONFIRM and was to be conducted only if the patient populations and treatment effects were similar between the studies
• This post hoc, integrated analysis assessed the efficacy and safety of TECFIDERA in newly diagnosed patients who had been diagnosed with RRMS within 1 year prior to the study and had not been previously treated with a disease-modifying therapy
• This integrated analysis included data from the intent-to-treat (ITT) population of DEFINE and CONFIRM, with a subset comprising the MRI cohort
• Efficacy was evaluated according to the DEFINE and CONFIRM efficacy endpoints at 2 years
• Safety was evaluated according to the incidence of adverse events in the DEFINE and CONFIRM trials
• DEFINE and CONFIRM were prospective, randomized, placebo-controlled, phase 3 studies. Eligible patients were randomized to receive placebo, TECFIDERA 240 mg BID, TECFIDERA 240 mg TID, or glatiramer acetate (reference comparator; CONFIRM only) for up to 96 weeks. Patients in the glatiramer acetate group were excluded for this post hoc analysis

Study Population

• The ITT population for this analysis comprised 2301 patients, of whom 678 met newly diagnosed criteria (n=223, 221, and 234 in the placebo, TECFIDERA BID, and TECFIDERA TID groups, respectively). A subset of these patients (n=100, 99, and 109 in the placebo, TECFIDERA BID, and TECFIDERA TID groups, respectively) comprised the MRI cohort

Inclusion Criteria

• Patients aged 18–55 years, diagnosed with RRMS according to the McDonald criteria, had an EDSS score of 0–5.0, inclusive, and had experienced at least one clinically documented relapse within 1 year prior to randomization or had at least one Gd+ lesion on a brain MRI obtained within 6 weeks prior to randomization

Key Exclusion Criteria

• Relapse or corticosteroid treatment within 50 days of randomization or prior treatment with glatiramer acetate within 3 months prior to randomization (DEFINE) or at any time (CONFIRM)

Study Outcomes

• Primary: PPR at 2 years for DEFINE and ARR at 2 years for CONFIRM
• Secondary: Time to 12-week disability progression, number of Gd+ lesions, number of new or enlarging T2 hyperintense lesions, and number of new T1 hypointense lesions all at 2 years

Study Limitations

• Post hoc analysis results should be interpreted with caution
• The study was not designed in advance to analyze the endpoints presented in the subgroup of newly diagnosed patients
• There is no universal criterion for newly diagnosed

^*ARR was calculated using a negative binomial regression model adjusted for baseline EDSS score (≤2.0 vs >2.0), baseline age (<40 vs ≥40 years), study, region, and number of relapses in the 1 year prior to DEFINE/CONFIRM study entry.

^†Estimated proportion of patients with disability progression at week 96 was derived using Kaplan-Meier analysis. HR, 95% CI, and P value were based on a stratified Cox proportional hazards model with study as the stratifying variable, adjusted for baseline EDSS score (as a continuous variable), baseline age (<40 vs ≥40), and region.

• Incidence of AEs is consistent with that of the overall integrated population in DEFINE/CONFIRM
• Most common AEs (incidence ≥10% and ≥3% more than placebo) for TECFIDERA: flushing, nasopharyngitis, headache, diarrhea, nausea, and abdominal pain
• Incidence of AEs leading to discontinuation of treatment in this subgroup was 5% and 12% in the placebo and TECFIDERA groups, respectively, compared with 12% and 14% in the overall safety population