Efficacy and safety of satralizumab from two phase 3 trials in neuromyelitis optica spectrum disorder
Zdenka Haskova, MD, PhD
Z. Haskova1, J. de Seze2, B. Weinshenker3, Y. Terada4, Y. Kawata4, A. Gianella-Borradori5*, C. von Büdingen6, G. Klingelschmitt6, A. Traboulsee7, T. Yamamura8
- Genentech, Inc., South San Francisco, CA
- Department of Neurology, Hôpital de Hautepierre
- Mayo Clinic, Rochester, MN, USA
- Chugai Pharmaceutical Co., Ltd, Tokyo, Japan
- Chugai Pharma USA, Inc., Berkeley Heights, NJ, USA *At the time of the study
- F. Hoffmann-La Roche Ltd, Basel, Switzerland
- The University of British Columbia, Vancouver, Canada
- National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Neuromyelitis optica spectrum disorder (NMOSD) is a lifelong, debilitating autoimmune disease of the central nervous system characterized by inflammatory lesions primarily in the optic nerves and spinal cord. Satralizumab is a humanized recycling monoclonal antibody that binds to the interleukin-6 (IL-6) receptor; IL-6 has been implicated in the pathophysiology of NMOSD. Satralizumab was evaluated in patients with NMOSD in two Phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). In this analysis, we assessed the efficacy and safety of satralizumab in the individual study and pooled patient populations, including the subgroup of patients who were seropositive for aquaporin-4 immunoglobulin G (AQP4-IgG).
Patients were randomized 1:1 (SAkuraSky; N=83) or 2:1 (SAkuraStar; N=95) to satralizumab (120 mg as monotherapy [SAkuraStar] or in combination with baseline immunosuppressants [SAkuraSky]) or placebo. The primary endpoint of both studies and the pooled analysis was time to first protocol-defined relapse (PDR). Between-group hazard ratios (HRs) were calculated based on Cox proportional hazards models.
Compared with placebo, satralizumab reduced the risk of PDR by 62% (HR, 0.38 [95% CI 0.16–0.88]) in SAkuraSky and by 55% (HR, 0.45 [95% CI 0.23–0.89]) in SAkuraStar (both p=0.018). In AQP4-IgG–seropositive patients, risk of PDR was reduced in SAkuraSky (satralizumab, n=27; placebo, n=28) by 79% (HR 0.21 [95% CI 0.06–0.75]) and in SAkuraStar (satralizumab, n=41; placebo, n=23) by 74% (HR 0.26 [95% CI 0.11–0.63]). In the pooled analysis, HR for time to first PDR was 0.42 (95% CI 0.25–0.71; 58% risk reduction satralizumab vs placebo). In AQP4-IgG–seropositive patients, the HR was 0.25 (95% CI 0.12–0.50; 75% risk reduction). Incidence of adverse events was similar in satralizumab and placebo groups; there were no deaths or anaphylactic reactions.
This analysis of data from two Phase 3 studies demonstrated the efficacy of satralizumab in reducing relapse risk in patients with NMOSD, particularly in AQP4-IgG–seropositive patients. Satralizumab had a favorable safety profile as monotherapy or in combination with immunosuppressants.