Date: 2014-09-11
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the Sixth Triennial Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS)
Company: BiogenIdec (USA - MA)
Product: Tecfidera® (dimethyl fumarate)
Action mechanism:
Disease: relapsing-remitting multiple sclerosis (RRMS)
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial
details: ENDORSE is an ongoing global, dose-blind, Phase 3 extension study to determine the long-term safety and efficacy of Tecfidera® (240 mg, BID or TID). The study has enrolled 1,738 patients with RRMS who completed the DEFINE or CONFIRM studies. Patients who received two years of Tecfidera® in DEFINE and CONFIRM continued on the same dose (BID or TID) in ENDORSE. Patients who previously received placebo or GA (CONFIRM only) were randomized 1:1 to Tecfidera® BID or TID. Patients participating in ENDORSE will be followed for up to eight years.
The primary objective of the study is to evaluate the long-term safety profile of Tecfidera® . Secondary objectives include: long-term efficacy of Tecfidera® on clinical outcomes and MS brain lesions on MRI scans and effects of Tecfidera® on quality of life measurements.
DEFINE (Determination of the Efficacy and safety of oral Fumarate IN relapsing-rEmitting MS) was a global, two-year, randomized, multi-center, double-blind, placebo-controlled, dose-comparison Phase 3 clinical trial that enrolled more than 1,200 patients with RRMS at 198 sites in 28 countries. The study evaluated Tecfidera® (240 mg, BID or TID) compared to placebo. The primary objective was to determine if Tecfidera® was effective in reducing the proportion of relapsing patients at two years. Secondary endpoints included reduction in the number of new or newly enlarging T2-hyperintense lesions and Gd+ lesions as measured by MRI, reduction in ARR, and reduction of disability progression as measured by EDSS. Safety and tolerability of Tecfidera® were also assessed.
CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting MS) was a global, two-year, randomized, multi-center, placebo-controlled, double-blind, dose-comparison Phase 3 clinical trial that enrolled more than 1,400 patients with RRMS at 200 sites in 28 countries. The study investigated Tecfidera® (240 mg, BID or TID) compared to placebo and included a reference comparator arm of glatiramer acetate (GA; 20 mg subcutaneous daily injection) versus 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. Secondary endpoints at two years included reduction in: the number of new or newly enlarging T2-hyperintense lesions and the number of new non-enhancing T1-hypointense lesions (MRI scans were obtained at a cohort of sites); the proportion of patients who relapsed; and progression of disability as measured by EDSS. Safety and tolerability of Tecfidera® were also assessed.
Latest
news: * On September 11, 2014, Biogen Idec announced that five-year results from the ENDORSE Phase 3 extension study show Tecfidera® (dimethyl fumarate) provides strong and sustained efficacy in a broad range of people living with relapsing-remitting multiple sclerosis (RRMS). These data will be presented at the Sixth Triennial Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS). Effect of TECFIDERA on No Evidence of Disease Activity: Another analysis from ENDORSE evaluated the long-term effects of Tecfidera® on the emerging measure of No Evidence of Disease Activity (NEDA) over five years. Patients were assessed annually and were considered to have NEDA if they had: no relapses, no 24-week confirmed disability progression, no Gd+ lesions, and no new or enlarging T2-hyperintense lesions. Results over five years show that the proportion of patients achieving NEDA annually was maintained in patients who continued on Tecfidera®, and was improved in patients who switched from placebo to treatment with Tecfidera® BID in the ENDORSE study. Long-term Follow-up of the Effect of Delayed-Release Dimethyl Fumarate on No Evident Disease Activity in Patients with Multiple Sclerosis - ENDORSE Safety: The safety profile of Tecfidera® observed in ENDORSE was consistent with the favorable findings reported in the DEFINE and CONFIRM studies. There were no new or worsening safety findings observed in patients who continued treatment with Tecfidera® from DEFINE and CONFIRM or in patients who switched to Tecfidera® therapy after the conclusion of the pivotal studies. All patients in ENDORSE had received treatment with Tecfidera® for at least five years if previously on Tecfidera® in DEFINE or CONFIRM, including some patients who had received Tecfidera® for up to seven and a half years cumulatively. Patients previously on placebo in DEFINE or CONFIRM had received Tecfidera® in ENDORSE for at least three years. The most common adverse events in patients who switched to Tecfidera® from placebo or GA were flushing and gastrointestinal (GI) events, the incidences of which were generally similar to what was observed in DEFINE and CONFIRM. In patients continuing on Tecfidera® therapy, the most common adverse events were MS relapse and nasopharyngitis (common cold).
ENDORSE Clinical Efficacy and MRI Outcomes: ENDORSE is a global, dose-blind extension study evaluating the long-term safety and efficacy of Tecfidera® (240 mg, dosed twice a day [BID] or three times a day [TID]). Patients who received up to two years of Tecfidera® in the pivotal Phase 3 DEFINE and CONFIRM studies continued on the same dose in ENDORSE. Patients who previously received placebo or glatiramer acetate (GA; 20 mg subcutaneous daily injection; CONFIRM only) in DEFINE and CONFIRM were randomized 1:1 to Tecfidera® BID or TID.
At five years (two years in DEFINE or CONFIRM and three years in ENDORSE), interim results show that patients who continued on Tecfidera® BID treatment experienced sustained clinical efficacy on relapse and disability progression endpoints as measured by annualized relapse rate (ARR) and 24-week Expanded Disability Status Scale (EDSS), similar to what was observed after two years in DEFINE and CONFIRM. These patients also maintained a low frequency of brain lesions over five years as measured by new or enlarging T2-hyperintense lesions, new non-enhancing T1-hypointense lesions and gadolinium-enhanced [Gd+] lesions.
Clinical Efficacy in Newly Diagnosed Patients: An analysis of data from ENDORSE evaluated the long-term efficacy of Tecfidera® in newly diagnosed patients, defined as those diagnosed within one year prior to enrolling in DEFINE or CONFIRM and either disease modifying treatment-naïve or previously treated with corticosteroids alone. Over the five-year observation period, newly diagnosed patients taking Tecfidera® BID experienced sustained reductions in relapses (measured by ARR and proportion of patients who relapsed), disability progression (measured by 24-week EDSS) and number of brain lesions. These effects are similar to the results reported for the overall ENDORSE study population, supporting the consistent efficacy of Tecfidera® in this subpopulation.
In patients continuing on, or new to, Tecfidera® treatment there was no overall increased risk of serious infections (including opportunistic infections) or malignancies. There was no overall increased risk of renal dysfunction, urinary events or hepatic adverse events in any treatment group; and mean white blood cell and lymphocyte counts remained stable.
