Contributions
Abstract: P607
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The Phase 3 DEFINE and CONFIRM studies demonstrated a favourable benefit-risk profile of delayed-release dimethyl fumarate (DMF), mainly in Caucasian MS patients.
Objectives: To study 24-week efficacy and safety outcomes of DMF in patients with relapsing MS from Asia-Pacific countries.
Methods: This was a 24-week, randomized, double-blind and placebo-controlled Phase 3 study. A total of 225 patients from Japan (n=114), South Korea, Taiwan, the Czech Republic and Poland were randomized 1:1 to receive DMF 240 mg twice daily or matching placebo. The primary endpoint is the total number of new gadolinium-enhancing (Gd+) lesions over 4 brain magnetic resonance imaging (MRI) scans at Week 12, 16, 20 and 24; the secondary endpoints are the total number of new Gd+ lesions from Baseline to Week 24 and the number of new or newly enlarging T2 lesions at Week 24 compared with Baseline. An open-label safety extension is ongoing.
Results: Two hundred thirteen patients completed this study. Compared with placebo, DMF reduced the mean number of new Gd+ lesions during Weeks 12-24 by 84% (P< 0.0001), mean number of new Gd+ lesions from Baseline to Week 24 by 75% (P< 0.0001), and mean number of new or newly enlarging T2-hypointense lesions at Week 24 by 63% (P< 0.0001). Commonly reported adverse events in DMF-treated patients included flushing and related symptoms (30% [DMF] vs 9% [placebo]) and gastrointestinal tolerability events (33% [DMF] vs 16% [placebo]). Mean absolute lymphocyte counts decreased by approximately 16% from Baseline to Week 24 in DMF-treated patients, remaining within normal limits at all time points. The overall incidence of infection was similar with placebo (42%) and DMF (41%). Both efficacy and safety results in Japanese and Asian subgroups were consistent with the overall study population.
Conclusions: These results indicate that the beneficial effects of DMF demonstrated in Caucasian patients extend to Asian (including Japanese) MS patients.
Disclosure:
Supported by: Biogen
Takahiko Saida: coordinating investigator; has received funding from, held board membership for, spoken at scientific meetings for, prepared manuscripts for, and had consulting agreements with Astellas, Biogen, Bayer-Schering, Daiichi-Sankyo, Eisai, Kaketsuken, Merck Serono, Mitsubishi-Tanabe, Nihon, Novartis, Ono , Sanofi, TDS Japan, and Teijin.
Takashi Yamamura: Multiple Sclerosis Center, National Center of Neurology and Psychiatry; member of scientific advisory boards for Biogen and Chugai; received research support from Asahi Kasei Kuraray, Chugai, Mitsubishi Tanabe, Ono, and Teva; received speaker honoraria from Abbot Japan, Astellas, Bayer, Biogen, Dainippon Sumitomo, Eisai, Mitsubishi Tanabe, Nihon, Novartis, and Santen; funded by the Japanese Ministry of Health, Labour and Welfare and the Japan Society for the Promotion of Science.
Takayuki Kondo: research support from Bayer HealthCare, Biogen, Novartis, Mitsubishi Tanabe, Eisai, and Takeda; speaker honoraria from Bayer, Biogen, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, and Novartis.
Jang Yun: employee of and holds stock/stock options in Biogen.
Minhua Yang: employee of and holds stock/stock options in Biogen.
Jie Li: employee of and holds stock/stock options in Biogen.
Lalitha Mahadavan: employee of and holds stock/stock options in Biogen.
Bing Zhu: employee of and holds stock/stock options in Biogen.
Sarah I Sheikh: employee of and holds stock/stock options in Biogen.
Abstract: P607
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The Phase 3 DEFINE and CONFIRM studies demonstrated a favourable benefit-risk profile of delayed-release dimethyl fumarate (DMF), mainly in Caucasian MS patients.
Objectives: To study 24-week efficacy and safety outcomes of DMF in patients with relapsing MS from Asia-Pacific countries.
Methods: This was a 24-week, randomized, double-blind and placebo-controlled Phase 3 study. A total of 225 patients from Japan (n=114), South Korea, Taiwan, the Czech Republic and Poland were randomized 1:1 to receive DMF 240 mg twice daily or matching placebo. The primary endpoint is the total number of new gadolinium-enhancing (Gd+) lesions over 4 brain magnetic resonance imaging (MRI) scans at Week 12, 16, 20 and 24; the secondary endpoints are the total number of new Gd+ lesions from Baseline to Week 24 and the number of new or newly enlarging T2 lesions at Week 24 compared with Baseline. An open-label safety extension is ongoing.
Results: Two hundred thirteen patients completed this study. Compared with placebo, DMF reduced the mean number of new Gd+ lesions during Weeks 12-24 by 84% (P< 0.0001), mean number of new Gd+ lesions from Baseline to Week 24 by 75% (P< 0.0001), and mean number of new or newly enlarging T2-hypointense lesions at Week 24 by 63% (P< 0.0001). Commonly reported adverse events in DMF-treated patients included flushing and related symptoms (30% [DMF] vs 9% [placebo]) and gastrointestinal tolerability events (33% [DMF] vs 16% [placebo]). Mean absolute lymphocyte counts decreased by approximately 16% from Baseline to Week 24 in DMF-treated patients, remaining within normal limits at all time points. The overall incidence of infection was similar with placebo (42%) and DMF (41%). Both efficacy and safety results in Japanese and Asian subgroups were consistent with the overall study population.
Conclusions: These results indicate that the beneficial effects of DMF demonstrated in Caucasian patients extend to Asian (including Japanese) MS patients.
Disclosure:
Supported by: Biogen
Takahiko Saida: coordinating investigator; has received funding from, held board membership for, spoken at scientific meetings for, prepared manuscripts for, and had consulting agreements with Astellas, Biogen, Bayer-Schering, Daiichi-Sankyo, Eisai, Kaketsuken, Merck Serono, Mitsubishi-Tanabe, Nihon, Novartis, Ono , Sanofi, TDS Japan, and Teijin.
Takashi Yamamura: Multiple Sclerosis Center, National Center of Neurology and Psychiatry; member of scientific advisory boards for Biogen and Chugai; received research support from Asahi Kasei Kuraray, Chugai, Mitsubishi Tanabe, Ono, and Teva; received speaker honoraria from Abbot Japan, Astellas, Bayer, Biogen, Dainippon Sumitomo, Eisai, Mitsubishi Tanabe, Nihon, Novartis, and Santen; funded by the Japanese Ministry of Health, Labour and Welfare and the Japan Society for the Promotion of Science.
Takayuki Kondo: research support from Bayer HealthCare, Biogen, Novartis, Mitsubishi Tanabe, Eisai, and Takeda; speaker honoraria from Bayer, Biogen, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, and Novartis.
Jang Yun: employee of and holds stock/stock options in Biogen.
Minhua Yang: employee of and holds stock/stock options in Biogen.
Jie Li: employee of and holds stock/stock options in Biogen.
Lalitha Mahadavan: employee of and holds stock/stock options in Biogen.
Bing Zhu: employee of and holds stock/stock options in Biogen.
Sarah I Sheikh: employee of and holds stock/stock options in Biogen.