Introduction
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, autoimmune inflammatory disorder of the central nervous system that predominantly affects the optic nerves and spinal cord. Its management remains challenging due to frequent relapses, which can lead to cumulative neurological deficits. The advent of targeted immunotherapies offers promising avenues for long-term disease control.
Satralizumab (SAT) is a monoclonal antibody that inhibits the interleukin-6 (IL-6) receptor, a cytokine implicated in the pathogenesis of NMOSD. Clinical trials, including SAkuraSky and SAkuraStar, demonstrated that SAT reduces relapse risk with a favorable safety profile. The ongoing SAkuraMoon open-label extension study evaluated the long-term safety and efficacy of SAT in patients with NMOSD, providing valuable insights into its sustained use.
Study Background and Rationale
The burden of NMOSD is significant, with relapses contributing to progressive disability. Existing therapies have limitations in efficacy, safety, or convenience. As IL-6 plays a key role in NMOSD pathogenesis, targeting this cytokine offers a disease-modifying approach. The SAkuraMoon study was designed to assess whether the benefits of SAT observed in shorter-term trials could be maintained over extended periods.
Study Design and Population
SAkuraMoon was a single-arm, open-label extension of the double-blind SAkuraSky and SAkuraStar trials. Patients who completed these core studies and consented to further treatment enrolled in SAkuraMoon, where they continued receiving 120 mg of subcutaneous SAT every four weeks, with some patients receiving concomitant immunosuppressive therapy (IST). The study population comprised 166 patients with NMOSD, primarily seropositive for aquaporin-4 immunoglobulin-G (AQP4-IgG+), which is associated with NMOSD pathology.
The study’s endpoints focused on safety, including adverse events (AEs) and infections, and efficacy measures such as the annualized relapse rate (ARR), time to first investigator-reported relapse (iPDR), severe relapses, and disability progression as measured by the EDSS.
Key Findings
Safety outcomes indicated that over a median exposure of nearly 7 years, the rates of AEs and serious AEs decreased compared to the initial double-blind phases. Specifically, adverse events occurred at a rate of approximately 299 per 100 patient-years, with serious adverse events at 8.1 per 100 patient-years. Importantly, infection rates remained consistent over time, with infections at 87.5 per 100 patient-years and serious infections at 2.4 per 100 patient-years. No fatalities or new safety signals emerged, supporting SAT’s long-term tolerability.
Efficacy results were compelling. In the AQP4-IgG+ subgroup, the adjusted annualized relapse rate was only 0.07, indicating a sustained suppression of disease activity. At 8.8 years, a significant proportion of patients remained relapse-free: 67% were free from any investigator-reported relapse, 89% from severe relapses, and 82% did not experience sustained worsening of disability as measured by EDSS.
These findings underscore the durable efficacy of SAT in controlling relapses and preventing disability accumulation, with safety outcomes supporting its long-term use.
Expert Commentary and Implications
The SAkuraMoon study provides robust evidence that sitralizumab maintains its disease-modifying effects over an extended period. Its favorable safety profile aligns with previous trial data, and long-term suppression of relapses could translate into improved quality of life and functional outcomes for patients.
Limitations include the open-label nature of the extension, potential selection bias, and the absence of a control group during the extension phase. Nevertheless, the consistent safety and efficacy signals support SAT as a valuable option for long-term management of AQP4-IgG+ NMOSD.
From a mechanistic perspective, IL-6 inhibition modulates multiple immune pathways involved in NMOSD, which likely contributes to the durable responses observed. Future studies could further elucidate biomarkers predictive of long-term response and explore combination strategies.
Conclusion
The SAkuraMoon extension trial confirms that satralizumab is a safe and effective long-term maintenance therapy for patients with AQP4-IgG+ NMOSD. Its sustained suppression of relapses and disability progression highlights its potential to modify the disease trajectory, emphasizing its role in the evolving landscape of NMOSD treatment.
Funding and Trial Registration
The study was registered on ClinicalTrials.gov (NCT02028884, NCT02073279, NCT04660539) and EudraCT (2020-003413-35). The research was funded by F. Hoffmann-La Roche Ltd.
References
Bennett JL, Fujihara K, Saiz A, Traboulsee AL, Greenberg BM, Weinshenker BG, Patti F, Kleiter I, Palace J, De Seze J, Evans R, Blondeau K, Klingelschmitt G, Vodopivec I, Rahim M, Yamamura T. Long-Term Efficacy and Safety of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder From the SAkuraMoon Open-Label Extension Study. Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200450. doi: 10.1212/NXI.0000000000200450. Epub 2025 Jul 31.
