Efficacy of satralizumab (SA237) in subgroups of patients in SAkuraSky: a Phase III double-blind, placebo-controlled, add-on study in patients with neuromyelitis optica spectrum disorder (NMOSD) (S43.008)

To evaluate the efficacy of satralizumab (SA237) in subgroups of the SAkuraSky study (NCT02028884).

Satralizumab, a recycling anti-IL-6 receptor monoclonal antibody, significantly reduced the risk of experiencing a protocol defined relapse (PDR) in NMOSD patients by 62% compared with placebo, in addition to baseline treatment in the overall population of the SAkuraSky study. At baseline, 66.3% of patients were AQP4-antibody (Ab) positive and 33.7% were AQP4-Ab negative.

SAkuraSky is a randomized, double-blind, phase 3 study of satralizumab compared to placebo as add-on to baseline treatment (immunosuppressants and/or corticosteroids, both at a stable dose). Subjects were randomized to satralizumab (120 mg s.c.) or placebo administered at weeks 0, 2, 4, and Q4W thereafter. The primary endpoint was time to first PDR, adjudicated by a clinical endpoint committee. Pre-specified subgroup analyses included assessing the response to treatment by AQP4-Ab serostatus, baseline treatment, and region. Between-group hazard ratios were based on Cox proportional hazards models.

Satralizumab showed a 79% risk reduction of PDR compared to placebo in the NMO/NMOSD AQP4-Ab positive subgroup (HR, 0.21; 95% CI, 0.06–0.75). The proportion relapse free at weeks 48 and 96 were 91.5% (95% CI, 69.6%–97.8%) and 91.5% (95% CI, 69.6%–97.8%) with satralizumab and 59.9% (95% CI, 36.3%–77.3%) and 53.3% (95% CI, 29.3%–72.4%) with placebo, respectively. For the NMO/NMOSD AQP4-Ab negative subgroup, satralizumab showed a risk reduction of PDR of 34% compared to placebo (HR, 0.66; 95% CI, 0.20–2.23), and the proportion relapse free at weeks 48 and 96 were 84.4% (95% CI, 50.4%–95.9%) and 56.3% (95% CI, 24.2%–79.2%) with satralizumab, and 75.5% (95% CI, 41.6%–91.4%) and 67.1% (95% CI, 34.2%–86.2%) with placebo, respectively.

The subgroup data show that satralizumab is effective in reducing PDR, especially in NMO/NMOSD AQP4-Ab positive patients. Results and conclusions from additional subgroups will be presented at the conference.

Disclosure: Dr. Yamamura has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Japan Ltd., Takeda Pharmaceutical Co., Ltd, Novartis Pharma K.K., Mitsubishi Tanabe Pharma Corp., Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co., Ltd. Medical Review Co. Ltd. Chiome Bioscience Inc. Miraca Research Institute. Dr. Yamamura has received compensation for serving on the Board of Directors of Mitsubishi Tanabe Pharma, Novartis, Nihon, Santen, Abbott Japan/Eisai, Biogen Japan, Dainippon Sumitomo, Bayer Holding, and Astellas Pharma Inc., and Takeda Pharmaceutical Co., Ltd. Dr. Yamamura has received research support from Chugai Pharmaceutical Co., Ltd., Biogen Japan Ltd., Novartis Pharma K.K., Chiome Bioscience Inc., Miraca Research Institute. Dr. Kleiter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Chugai, Merck, Novartis Pharmaceuticals, Roche, and Sanofi Genzyme. Dr. Fujihara has received personal compensation from Biogen, Mitsubishi-Tanabe, Takeda, Novartis, Eisai, Nihon, Teijin, Ono, Asahi Medical, Apothecom. Dr. Palace has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide and ARGENX. Dr. Palace has received research support from MS society, Guthie Jackson Foundation, NIHR, Oxford Health Services Research Committee, EDEN, MRC, GMSI, and John Fell. Dr. Greenberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Alexion, EMD Serono. Dr. Greenberg has received research support from Chugai, Medimmune, Genentech, MedDay, PCORI, NIH, NMSS and Guthy Jackson Charitable Foundation for NMO. Dr. Zakrzewska-Pniewska has received and/or receives support for scientific meetings and honoraria for advisory work from Roche, Chugai, Biogen, Merck, Novartis, Bayer, Medimmune, Teva, Sanofi Aventis and Allergan. Dr. Patti has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Bayer, Biogen, Celgene, Merck, Myalin, Novartis, Roche, Sanofi-Genzyme and Teva. Dr. Patti has received research support from MIUR (Ministero Italiano della Università della Ricerca Scientifica), FISM (Fondazione Italiana Sclerosi Multipla), Biogen and Merck. Dr. Tsai has nothing to disclose. Dr. Saiz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck-Serono, Sanofi, Biogen, Roche, TEVA, Novartis, and Bayer-Schering. Dr. Haramura has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Chugai Pharmaceutical Co., Ltd. Dr. Terada has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Chugai Pharmaceutical Co., Ltd. Dr. Kawata has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Chugai Pharmaceutical Co., Ltd. Dr. De Seze has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Sanofi-Genzyme, Teva, Novartis, Roche, Chugai, and Alexion. Dr. De Seze has received research support from Sanofi.