Contributions
Abstract: P631
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favourable benefit-risk in patients (pts) with relapsing-remitting multiple sclerosis (RRMS) in clinical trials. ENDORSE (NCT00835770) is a 12-yr extension of the Phase 3 DEFINE/CONFIRM studies.
Objectives: Report 7-yr clinical efficacy outcomes in RRMS pts treated with DMF.
Methods: Pts randomized in DEFINE/CONFIRM to DMF 240 mg twice (BID) or three times daily (TID) continued on the same dosage in ENDORSE. Pts randomized to placebo (PBO) or glatiramer acetate (CONFIRM only) were re-randomized 1:1 to DMF BID or TID. Pts switched to DMF BID after regulatory approval. Here we report results for DMF BID. “Newly diagnosed” was defined as MS diagnosis ≤1 yr prior to parent study entry and either treatment-naïve or previously treated with corticosteroids alone. As of 15 April 2015, the minimum follow-up was approximately 6 yrs: pts initially randomized to DMF BID in DEFINE/CONFIRM who continued on DMF BID in ENDORSE (DMF/DMF) received approximately ≥6 yrs continuous DMF treatment; pts initially randomized to PBO who switched to DMF BID in ENDORSE (PBO/DMF) received 2 yrs PBO followed by approximately ≥4 yrs DMF.
Results: In the newly diagnosed population (n=144 DMF/DMF; n=85 PBO/DMF), at 6 yrs (ENDORSE Yr 4), annualized relapse rate (ARR) (95% CI) was 0.14 (0.10, 0.19) in DMF/DMF and 0.17 (0.11, 0.25) in PBO/DMF; rate ratio (95% CI) for DMF/DMF vs PBO/DMF was 0.81 (0.51, 1.31) (P=0.3988). In PBO/DMF, ARR (95% CI) was 0.26 (0.18, 0.37) from Yrs 0-2 (DEFINE/CONFIRM) and 0.10 (0.06, 0.16) from Yrs 3-6 (ENDORSE); rate ratio (95% CI) for Yrs 3-6 vs 0-2 was 0.39 (0.24, 0.63; P< 0.0001). Kaplan-Meier estimated proportion (95% CI) of pts with 24-wk confirmed disability progression (CDP) was 15.7% (10.3%, 23.7%) in DMF/DMF and 24.3% (15.9%, 36.2%) in PBO/DMF; hazard ratio (95% CI) for DMF/DMF vs PBO/DMF was 0.51 (0.27, 0.97; P=0.0397). Over 6 yrs, 56.3% DMF/DMF and 50.6% PBO/DMF pts remained free from relapses and CDP. Updated results from the 7-yr interim analysis will be presented.
Conclusions: The ARR and proportion of pts with 24-wk CDP remained low in pts treated with DMF over 6 yrs. In PBO/DMF, ARR was significantly reduced after switching to DMF. Pts receiving continuous DMF treatment had substantially lower risk for 24-wk CDP over 6 yrs vs those who received delayed treatment. Over 50% of pts in the DMF/DMF and PBO/DMF groups remained free from relapses and 24-wk CDP over 6 yrs.
Disclosure:
Supported by: Biogen.
Ralf Gold: honoraria from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders; research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience.
Gavin Giovannoni: honoraria from AbbVie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex; compensation from Elsevier as co-chief editor of MS and Related Disorders; research grant support from Biogen, Ironwood, Merck Serono, Merz, and Novartis.
J Theodore Phillips: served as a consultant for Acorda, Biogen, Genzyme, Merck Serono, and Sanofi; research support from Roche.
Robert J Fox: served as a consultant for Biogen, MedDay, Novartis, Questcor, Teva, and Xenoport; served on advisory committees for Biogen and Novartis; research grant funding from Novartis.
Annie Zhang: employee of and holds stock/stock options in Biogen.
Catherine Taylor: employee of and holds stock/stock options in Biogen.
Jing L Marantz: employee of and holds stock/stock options in Biogen.
Abstract: P631
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favourable benefit-risk in patients (pts) with relapsing-remitting multiple sclerosis (RRMS) in clinical trials. ENDORSE (NCT00835770) is a 12-yr extension of the Phase 3 DEFINE/CONFIRM studies.
Objectives: Report 7-yr clinical efficacy outcomes in RRMS pts treated with DMF.
Methods: Pts randomized in DEFINE/CONFIRM to DMF 240 mg twice (BID) or three times daily (TID) continued on the same dosage in ENDORSE. Pts randomized to placebo (PBO) or glatiramer acetate (CONFIRM only) were re-randomized 1:1 to DMF BID or TID. Pts switched to DMF BID after regulatory approval. Here we report results for DMF BID. “Newly diagnosed” was defined as MS diagnosis ≤1 yr prior to parent study entry and either treatment-naïve or previously treated with corticosteroids alone. As of 15 April 2015, the minimum follow-up was approximately 6 yrs: pts initially randomized to DMF BID in DEFINE/CONFIRM who continued on DMF BID in ENDORSE (DMF/DMF) received approximately ≥6 yrs continuous DMF treatment; pts initially randomized to PBO who switched to DMF BID in ENDORSE (PBO/DMF) received 2 yrs PBO followed by approximately ≥4 yrs DMF.
Results: In the newly diagnosed population (n=144 DMF/DMF; n=85 PBO/DMF), at 6 yrs (ENDORSE Yr 4), annualized relapse rate (ARR) (95% CI) was 0.14 (0.10, 0.19) in DMF/DMF and 0.17 (0.11, 0.25) in PBO/DMF; rate ratio (95% CI) for DMF/DMF vs PBO/DMF was 0.81 (0.51, 1.31) (P=0.3988). In PBO/DMF, ARR (95% CI) was 0.26 (0.18, 0.37) from Yrs 0-2 (DEFINE/CONFIRM) and 0.10 (0.06, 0.16) from Yrs 3-6 (ENDORSE); rate ratio (95% CI) for Yrs 3-6 vs 0-2 was 0.39 (0.24, 0.63; P< 0.0001). Kaplan-Meier estimated proportion (95% CI) of pts with 24-wk confirmed disability progression (CDP) was 15.7% (10.3%, 23.7%) in DMF/DMF and 24.3% (15.9%, 36.2%) in PBO/DMF; hazard ratio (95% CI) for DMF/DMF vs PBO/DMF was 0.51 (0.27, 0.97; P=0.0397). Over 6 yrs, 56.3% DMF/DMF and 50.6% PBO/DMF pts remained free from relapses and CDP. Updated results from the 7-yr interim analysis will be presented.
Conclusions: The ARR and proportion of pts with 24-wk CDP remained low in pts treated with DMF over 6 yrs. In PBO/DMF, ARR was significantly reduced after switching to DMF. Pts receiving continuous DMF treatment had substantially lower risk for 24-wk CDP over 6 yrs vs those who received delayed treatment. Over 50% of pts in the DMF/DMF and PBO/DMF groups remained free from relapses and 24-wk CDP over 6 yrs.
Disclosure:
Supported by: Biogen.
Ralf Gold: honoraria from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders; research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience.
Gavin Giovannoni: honoraria from AbbVie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex; compensation from Elsevier as co-chief editor of MS and Related Disorders; research grant support from Biogen, Ironwood, Merck Serono, Merz, and Novartis.
J Theodore Phillips: served as a consultant for Acorda, Biogen, Genzyme, Merck Serono, and Sanofi; research support from Roche.
Robert J Fox: served as a consultant for Biogen, MedDay, Novartis, Questcor, Teva, and Xenoport; served on advisory committees for Biogen and Novartis; research grant funding from Novartis.
Annie Zhang: employee of and holds stock/stock options in Biogen.
Catherine Taylor: employee of and holds stock/stock options in Biogen.
Jing L Marantz: employee of and holds stock/stock options in Biogen.