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Long-term Efficacy and Safety of Satralizumab in Adults with AQP4-IgG+ Neuromyelitis Optica Spectrum Disorder: Results from the Phase 3 SAkura studies
Shervin Gholizadeh Moghaddam
S. Gholizadeh1, J.L. Bennett2, E. Fox3, B. Greenberg4, B.G. Weinshenker5, A. Traboulsee6, M.R. Yeaman7, K. Blondeau8, K. Weber8, I. Vodopivec8, M. Levy9
1 Genentech, Inc., South San Francisco, CA, USA
2 University of Colorado School of Medicine, Aurora, CO, USA
3 Central Texas Neurology Consultants, Round Rock, TX, USA
4 University of Texas Southwestern Medical Center, Dallas, TX, USA
5 Mayo Clinic, Rochester, MN, USA
6 University of British Columbia, Vancouver, Canada
7 David Geffen School of Medicine at UCLA, Los Angeles, and Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA
8 F. Hoffmann-La Roche Ltd, Basel, Switzerland
9 Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Satralizumab reduced the risk of protocol-defined relapse (PDR) vs placebo in the double-blind periods (DBP) of two trials in neuromyelitis optica spectrum disorder (NMOSD): SAkuraSky (NCT02028884; satralizumab + baseline immunosuppressants [IST]) and SAkuraStar (NCT02073279; satralizumab monotherapy). Satralizumab is FDA-approved for the treatment of adults with aquaporin-4-immunoglobulin-G-seropositive (AQP4-IgG+) NMOSD. We present long-term efficacy and safety data from the DBP and open-label extension (OLE) of these studies.
Satralizumab 120 mg or placebo was administered at Weeks 0, 2, 4 and Q4W in the DBP; patients could then enter the OLE (same dosing schedule). PDRs in the DBP were adjudicated by a Clinical Endpoint Committee; PDRs in the OLE were determined by the investigator (iPDRs). Current analyses included all AQP4-IgG+ adults who received ≥1 dose of satralizumab in the DBP and/or OLE (overall satralizumab treatment [OST] period, data cutoff: Feb 22, 2021). Efficacy analyses assessed the annualised iPDR rate (ARR), time to first iPDR, severe iPDR (≥2 point increase in the Expanded Disability Status Scale [EDSS] score), and sustained EDSS worsening (EDSS increase of ≥2, ≥1, or ≥0.5 points for patients with baseline scores of 0, 1–5, or ≥5.5, respectively, confirmed ≥24 weeks post-initial-worsening). Safety assessments compared rates of adverse events (AEs) per 100 patient-years (PY) in the OST period vs the DBPs.
106 AQP4-IgG+ adults were included (SAkuraSky: 44; SAkuraStar: 62). Median (range) duration of satralizumab exposure was 5.4 (0.1–7.0) years in SAkuraSky and 4.0 (0.1–6.0) years in SAkuraStar. The overall ARR (95% CI) in the OST was 0.11 (0.07–0.17) in SAkuraSky and 0.08 (0.05–0.13) in SAkuraStar; the ARR remained stable throughout the studies. At Week 192 (3.7 years) in SAkuraSky and SakuraStar, 74% and 73% of patients had no iPDR, 94% and 90% had no severe iPDR, and 89% and 86% had no sustained worsening of EDSS, respectively. Rates of serious AEs (95% CI) in the OST period were comparable with the DBP (serious AEs: SAkuraSky 13.7 [8.9–20.1]/100 PY; SAkuraStar 10.6 [6.9–15.6]/100 PY). Rates of infections and serious infections in the OST period were comparable with the DBP and did not increase over time. No deaths or anaphylactic reactions to satralizumab were reported in either study.
Satralizumab efficacy and its favorable safety profile are sustained with long-term treatment.