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TECFIDERA® (DIMETHYL FUMARATE) REAL-WORLD STUDIES AFFIRM SUSTAINED EFFICACY AND DEMONSTRATE 9-YEAR SAFETY PROFILE

Biogen
Posted on: 14 Sep 16

Maidenhead, UK – 14th September, 2016 – Biogen (NASDAQ: BIIB) announce new TECFIDERA (dimethyl fumarate) data at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in London, England. The data presented, from both real-world and clinical settings, demonstrate that dimethyl fumarate delivered consistent1 and sustained efficacy2 among patients with relapsing-remitting multiple sclerosis (RRMS), and adds to its well-characterised safety profile for up to nine years of treatment.3

 

Real world findings demonstrate efficacy of dimethyl fumarate versus other MS therapies

Retrospective results from the worldwide MSBase registry show that dimethyl fumarate reduced the risk of first relapse versus interferons by 26% (n=420 matched pairs; HR 0.74; 95% CI 0.57, 0.97; p=0.027), glatiramer acetate by 28% (n=382; 0.72; 0.54, 0.95; p=0.022) and teriflunomide by 34% (n=256; 0.66; 0.45, 0.99; p=0.042). In the primary analysis, no significant difference was found versus fingolimod-treated patients (n=415; 1.03; 0.73, 1.46; reference = FTY).1 Time to first relapse was measured using binomial propensity score matching.

 

“The MSBase registry is one of the largest sources of real-world data and includes nearly 40,000 MS patients across 72 countries. Our analysis shows that dimethyl fumarate significantly reduced the risk of first relapse compared to platform therapies and teriflunomide, and had comparable efficacy to fingolimod,” said H. Butzkueven, Associate Professor in the Department of Medicine, University of Melbourne and one of the investigators for the study.

 

As a secondary endpoint, the study also demonstrated similar and consistently lower annualised relapse rates (ARR) for dimethyl fumarate-treated patients versus those treated with interferons (0.23 [95% CI 0.19, 0.27] vs 0.26 [0.24, 0.29]), glatiramer acetate (0.24 [0.19, 0.28] vs 0.26 [0.23, 0.29]) and teriflunomide (0.17 [0.13, 0.22] vs 0.27 [0.22, 0.33]). ARR for dimethyl fumarate-treated patients was found to be similar but higher versus fingolimod-treated patients (0.22 [0.18, 0.27] vs 0.19 [0.17, 0.23]).1 Positive ARR findings were also reported in a second real-world study analysing data from over 3,500 dimethyl fumarate-treated patients from a US Commercial Claims Database. An average reduction in ARR of -0.11 (0.41 vs 0.30; p<0.05) was demonstrated in the year following initiation of dimethyl fumarate versus the year before initiation.4

 

“These real-world findings demonstrate on a global scale the results observed during the dimethyl fumarate clinical trial program, and continue to support the use of dimethyl fumarate to improve outcomes for people living with relapsing-remitting MS” said Ralph Kern, SVP, Worldwide Medical, Biogen.

 

The MSBase registry data also found that approximately twice as many dimethyl fumarate-treated patients discontinued treatment after six months of continuous therapy relative to fingolimod (HR 2.39; 95% CI 1.78, 3.20) and interferons (HR 1.40; 95% CI 1.07, 1.83).1 No difference was found versus glatiramer acetate (HR 1.18; 95% CI 0.89, 1.56) or teriflunomide (HR 0.95; 95% CI 0.66, 1.37).1

 

The use of patient coaching to reduce discontinuation rates was demonstrated in a retrospective real-world study. In patients treated with dimethyl fumarate, rates were reduced in coached patients by up to 48% versus controls (5.7%, 17.1% and 29.2% of coached patients [n=4750] stopped therapy after 3, 12 and 24 months, versus 10.4%, 25.2% and 56.4% of controls [n=3266], respectively).5

 

Reasons for therapy discontinuation differed between coached and control patients, with partly manageable side effects found to be the main reason for discontinuation for controls. These results could indicate the potential for patient coaching to play an essential role in overcoming such side effects for dimethyl fumarate patients.5

 

Additional real-world data presented by Biogen demonstrated that the safety profile of dimethyl fumarate remained consistent over nine years,3 and its overall benefit-risk remained favourable.6 These data also further substantiate current guidance for monitoring absolute lymphocyte counts (ALC) to mitigate the risk of moderate to severe prolonged lymphopenia during treatment with dimethyl fumarate.6

 

Data from ENDORSE further clarify benefits of dimethyl fumarate for newly-diagnosed patients

New 7-year data from the ENDORSE study, an extension to the DEFINE and CONFIRM clinical trials, demonstrated that ARR remained low at 7 years for both treatment groups (0.13 [95% CI 0.10–0.18] with dimethyl fumarate; 0.16 [95% CI 0.11–0.24] for patients switched from placebo). Switch patients experienced a 61% relative reduction in ARR following the switch to dimethyl fumarate after 2 years on placebo (ARR 0.26 [95% CI 0.18–0.37] vs 0.10 [0.07–0.15]; p<0.0001).2 These findings illustrate the potential of dimethyl fumarate to provide positive clinical outcomes over the long-term for people with relapsing remitting MS.

 

In addition, estimated 24-week confirmed disability progression (CDP) was 18.0% (95% CI 12.0–26.4) in the dimethyl fumarate group versus 26.4% (95% CI 17.4–38.7) in the switch group, representing a 41% risk reduction (95% CI 0.32–1.10, p=0.0979).2

 

ENDS

 

About ENDORSE
ENDORSE is an ongoing global, dose-blind, phase 3 extension study to determine the long-term safety and efficacy of dimethyl fumarate (240 mg, BD or TDS). The study has enrolled 1,738 patients with RRMS who completed the DEFINE or CONFIRM studies. Patients who received two years of dimethyl fumarate in DEFINE and CONFIRM continued on the same dose (BD or TDS) in ENDORSE. Patients who previously received placebo or glatiramer acetate (CONFIRM only) were randomised 1:1 to dimethyl fumarate BD or TDS. Following dimethyl fumarate approval at a dose of 240 mg BD, all subjects continuing in this study received open-label dimethyl fumarate 240 mg BD. 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 dimethyl fumarate. Secondary objectives include: long-term efficacy of dimethyl fumarate on clinical outcomes and MS brain lesions on MRI scans; and effects of dimethyl fumarate on quality of life measurements.

 

About DEFINE and CONFIRM
DEFINE (Determination of the Efficacy and safety of oral Fumarate IN relapsing-rEmitting MS) was a global, two-year, randomised, multi-centre, 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 dimethyl fumarate (240 mg, BD or TDS) compared to placebo. The primary objective was to determine if dimethyl fumarate 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 gadolinium-enhancing (Gd+) lesions as measured by MRI; ARR; and disability progression as measured by the Expanded Disability Status Scale (EDSS). Safety and tolerability of dimethyl fumarate were also assessed.

 

CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting MS) was a global, two-year, randomised, multi-centre, 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 dimethyl fumarate (240 mg, BD or TDS) 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 dimethyl fumarate 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 dimethyl fumarate were also assessed.

 

About TECFIDERA® (Dimethyl fumarate)

Dimethyl fumarate is an oral therapy for relapsing-remitting MS, the most common form of MS. In clinical trials, the most common adverse events associated with dimethyl fumarate were flushing and gastrointestinal (GI) events. Other side effects included a decrease in mean lymphocyte counts generally during the first year of treatment, which usually plateaued. Dimethyl fumarate is contraindicated in patients with a known hypersensitivity to dimethyl fumarate or any of the excipients. Rare cases of PML have been seen with dimethyl fumarate patients in the setting of moderate to severe prolonged lymphopenia.

 

Dimethyl fumarate is currently approved in the United States, the European Union, Canada, Australia and Switzerland. For the full summary of product characteristics, please visit www.medicines.org.uk/emc/medicine/28593.

 

About Biogen

Through cutting-edge science and medicine, Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological, autoimmune and rare diseases. Founded in 1978, Biogen is one of the world’s oldest independent biotechnology companies and patients worldwide benefit from its leading multiple sclerosis and innovative haemophilia therapies. For more information, please visit www.biogen.uk.com.

 

References:

 

1. Spelman T, et al. Comparative analysis of MS outcomes in dimethyl fumarate-treated patients relative to propensity matched fingolimod, interferon, glatiramer acetate, or teriflunomide. P1157. The 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.

 

2. Gold R, et al. Seven-year follow-up of the efficacy of delayed-release dimethyl fumarate in newly diagnosed patients with relapsing-remitting multiple sclerosis: integrated analysis of DEFINE, CONFIRM, and ENDORSE. P631. The 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.

 

3. Fox RJ, et al. Absolute lymphocyte count and lymphocyte subset profiles during long-term treatment with delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis. P716. The 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.

 

4. Boster A, et al. Annual relapse rates in multiple sclerosis patients treated with different disease-modify therapies – findings from a real world setting. EP1481. The 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.

 

5. Begus-Nahrmann Y, et al. The potential of individualized patient coaching to optimize treatment with delayed-release dimethyl fumarate: a retrospective analysis of patients with multiple sclerosis treated in a real-world setting. P1214. The 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.

 

6. Buckle G, et al. Effect of delayed-release dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis: a retrospective, multicentre, observational study (REALIZE). EP1495. The 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016. 

Editor's Details

Sameena Conning

Last updated on: 14/09/2016

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