Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar

Abstract

Background: This analysis evaluated long-term safety findings from the SAkuraSky and SAkuraStar studies with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD).

Methods: SAkuraSky (satralizumab in combination with baseline immunosuppressive therapy; IST) and SAkuraStar (satralizumab monotherapy) are international, multicenter, randomized, placebo-controlled, phase 3 studies consisting of a double-blind (DB) period followed by an open-label extension (OLE). The overall satralizumab treatment (OST) period safety population comprised patients receiving ≥1 dose of satralizumab in the DB and/or OLE periods (cut-off date: 22 February 2021). Safety was evaluated in the DB and OST periods.

Results: In the SAkuraSky DB period, patients received satralizumab (n = 41) or placebo (n = 42) in addition to stable baseline IST; 75 patients were included in the OST population. In the SAkuraStar DB period, 63 patients received satralizumab monotherapy and 32 received placebo; 91 patients were included in the OST population. Median treatment exposure in the OST period was 4.4 years (range 0.1-7.0) in SAkuraSky and 4.0 years (range 0.1-6.1) in SAkuraStar. Rates of adverse events (AEs per 100 patient-years) and serious AEs in the OST period were comparable with satralizumab and placebo in the DB periods of both studies. Similarly, overall rates of infections and serious infections were consistent between the OST and DB periods with satralizumab, with no increase in rates of infections or serious infections over time. In the OST periods, longer exposure to satralizumab was not associated with a higher risk of severe (grade ≥3) laboratory changes versus the DB periods. No deaths or anaphylactic reactions to treatment with satralizumab were reported during the OST periods of both studies.

Conclusion: The safety profile of satralizumab as a monotherapy or in combination with IST was maintained in the OLE, and no new safety concerns versus the DB period were observed.

Clinical trial registration: ClinicalTrials.gov identifiers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar).

Keywords: All clinical trials; All demyelinating disease (CNS); Autoimmune diseases; Devic's syndrome; Neuromyelitis optica spectrum disorder; Patient safety.

Conflict of interest statement

Declaration of Competing Interest This study was sponsored by F. Hoffmann-La Roche. Takashi Yamamura served on scientific advisory boards for Biogen, Takeda, Sumitomo, Novartis, and Chugai. He receives consulting fees from Biogen, Takeda, Mitsubishi Tanabe, Novartis, Roche, and Chugai. He carried out contracted research in Mitsubishi Tanabe, Novartis, Chugai, Sanofi, Chiome Bioscience, and Miraca Holdings (within the contract period but no deposit). He received speaker honoraria from Chugai, Takeda, Biogen, and Sumitomo. Brian G. Weinshenker reports consulting fees from UCB Biosciences, Mitsubishi Tanabe, Genentech, and Roche, and speaking fees from Genentech, Roche, and Novartis; he participated on the Attack Adjudication Committee for Alexion and Horizon Therapeutics (formerly MedImmune/Viela Bio). He reports personal fees from Chugai. He has a patent NMO-IgG for diagnosis of neuromyelitis optica with royalties received from RSR Ltd, Oxford University, Hospices Civils de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR. Michael R. Yeaman received grants from the US National Institutes of Health and the US Department of Defense, and consulting fees from Roche, Horizon, and Alexion. He is a founder and shareholder in NovaDigm Therapeutics, Inc. and Metacin, Inc. He serves on the Genentech-Roche Strategic Scientific Committee for NMOSD and is Chair Medical Advisor to the Guthy-Jackson Charitable Foundation for NMOSD. Jerome De Seze received grants and personal fees from Roche, personal fees from Chugai, and has served on advisory boards in the expert committee for the clinical trial conducted by Chugai. Francesco Patti has served on the scientific advisory boards for Almirall, Bayer, Biogen, Calgene, Merck, Novartis, Roche, Sanofi, and TEVA; he also received speaker honoraria from the aforementioned companies and research grants for his department from Biogen and Merck. Patricia Lobo is an employee of ApotheCom, who is paid to provide medical writing assistance for F. Hoffmann-La Roche Ltd. H.-Christian von Büdingen, Xiujing Kou, and Kristina Weber are employees of F. Hoffmann-La Roche Ltd. Benjamin Greenberg received consulting fees from Alexion, Novartis, EMD Serono, Viela Bio, Genentech/Roche, Greenwich Biosciences, Axon Advisors, Rubin Anders, ABCAM, Signant, IQVIA, Sandoz, Druggability Technologies, Genzyme, and Immunovant. He receives contracted research fees from Clene Nanomedicine. He receives royalties from UpToDate.

Copyright © 2022. Published by Elsevier B.V.