Satralizumab 120mg/1ml solution for injection pre-filled syringes

BACKGROUND: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis. METHODS: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally. Eligible patients were aged 12 years and older, with seropositive generalised myasthenia gravis (autoantibodies to the acetylcholine receptor [AChR-IgG], muscle-specific kinase [MuSK-IgG], or low-density lipoprotein receptor-related protein 4 [LRP4-IgG]), a Myasthenia Gravis Foundation of America severity class II-IV, a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 5 or more (non-ocular contribution >50%), and use of stable background therapy. Patients were randomly assigned (1:1) with a permuted-block randomisation method to receive subcutaneous satralizumab (120 mg for bodyweight ≤100 kg; 180 mg for bodyweight >100 kg) or placebo at weeks 0, 2, 4, and every 4 weeks thereafter until week 24. Randomisation was stratified according to background therapy, autoantibody type, and geographical region. The primary efficacy endpoint was mean change from baseline in total MG-ADL score at week 24 in the modified intention-to-treat population (all randomised AChR-IgG-positive patients who completed at least one post-baseline MG-ADL assessment). Safety was assessed in all randomly assigned patients who received at least one dose of study drug. The open-label extension was terminated early because of the sponsor's decision to halt further development of satralizumab for treatment of generalised myasthenia gravis. This trial is registered with ClinicalTrials.gov, NCT04963270, and EudraCT, 2020-004436-21. FINDINGS: Between Oct 19, 2021, and Aug 15, 2023, 188 patients were randomly assigned to satralizumab (n=96) or placebo (n=92). 166 AChR-IgG-positive patients (80 in the placebo group and 86 in the satralizumab group) were included in the modified intention-to-treat population. At week 24, statistically significant yet small improvements in MG-ADL score were observed with satralizumab versus placebo (adjusted mean -3·59, 95% CI -4·15 to -3·02 vs -2·57, -3·25 to -1·88; difference -1·02, -1·88 to -0·16; p=0·0120). The proportion of patients with at least one adverse event during the double-blind period was slightly higher in patients treated with satralizumab compared with patients treated with placebo (86 [90%] patients vs 67 [73%] patients). Three serious adverse events (in three [3%] patients) were reported in the satralizumab group (pneumonia, pyelonephritis, and increased lipase) compared with nine (in six [7%] patients) serious adverse events in the placebo group (COVID-19, COVID-19 pneumonia, bacterial urinary tract infection, chest pain, back pain, and rosacea). There were no deaths or adverse events of special interest. INTERPRETATION: Satralizumab was well tolerated and resulted in small improvements in patient-reported and clinician-reported outcomes compared with placebo at week 24 in patients with AChR-IgG-positive generalised myasthenia gravis. Further research analysing the immunological underpinnings of the observed clinical response to IL-6 signalling inhibition in patients with generalised myasthenia gravis and exploring the role of IL-6 in autoantibody-mediated diseases is warranted. FUNDING: F Hoffmann La Roche.

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BACKGROUND: Satralizumab is approved in Japan for relapse prevention of neuromyelitis optica spectrum disorder (NMOSD) in aquaporin-4 immunoglobulin G-seropositive (AQP4[+]) patients. However, clinical trial data for Japanese patients are limited. METHODS: SAkuraBeyond, an ongoing real-world observational study (UMIN000050027), evaluates NMOSD relapse over 2.5 years among satralizumab-treated patients with AQP4[+] NMOSD in Japan (25 sites). Herein, we present a 26-week interim effectiveness analysis. Patient data were derived from medical chart review and electronic case report forms. RESULTS: Of the 125 enrolled patients who initiated satralizumab, 124 were included in the study (mean age, 51.1 years; female, 93.5 %; mean disease duration, 7.0 years). At week 26, 120 patients were relapse-free (12 withdrew from satralizumab). The annualized relapse rate [95 % confidence interval (CI)] was 0.069 [0.026-0.183] at week 26 after satralizumab initiation and 0.445 [0.342-0.580] within 52 weeks before satralizumab initiation. The relapse-free rate [95 % CI] at week 26 was 96.6 % [91.2-98.7]. Four patients had relapses, of whom 1 discontinued satralizumab. Three recorded a modified Rankin Scale of ≤3 (1 with unknown status). The mean oral glucocorticoid (GC) dose reduced from baseline to 26 weeks of satralizumab treatment; the GC dose was reduced in 71.3 % of patients treated with oral GC >0 mg at baseline. Azathioprine and tacrolimus doses could be reduced to 0 mg/day in 35.3 % and 26.2 % of relapse-free patients, respectively, at week 26. CONCLUSION: The 6-month relapse-free rate after satralizumab treatment was 96.6 %. Satralizumab use permitted dose reduction of concomitant oral GC and immunosuppressants over 26-weeks.

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Currently, three monoclonal antibodies (MABs) have received regulatory approval from the federal agency, the United States Food and Drug Administration (USFDA), for the medical management of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab was the third approved therapy after MABs like eculizumab and inebilizumab for NMOSD, an uncommon but severe enfeebling autoimmune neurological disease. Satralizumab, a humanized monoclonal antibody, exerts its action in NMOSD by acting against cytokine interleukin-6 (IL-6), a foremost mediator in the pathological process of NMOSD. Two pivotal clinical trials carried out in NMOSD patients had established that satralizumab significantly decreased the rate of relapse in patients suffering from NMOSD as opposed to placebo. The trials also demonstrated that satralizumab is relatively safe. Thus, satralizumab provides an efficacious and safe treatment option for this rare, disabling central nervous system (CNS) disease. Our review aimed to elucidate the pharmacological characteristics of satralizumab and illustrate the available evidence regarding its safety and efficacy in patients with NMOSD.

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), a humanized anti-interleukin-6 (IL-6) receptor monoclonal recycling antibody, has been developed by Chugai Pharmaceutical and Roche for the treatment of neuromyelitis optica spectrum disorder (NMOSD). In June 2020, based on positive results from two pivotal phase III trials, subcutaneous satralizumab received its first global approval in Canada for the treatment of NMOSD in adults and children aged ≥ 12 years who are aquaporin 4 water channel autoantibody (AQP4-IgG) seropositive. Satralizumab was subsequently approved in Japan, Switzerland and the USA. Satralizumab is under regulatory review in the EU, and is undergoing clinical development in several countries worldwide. This article summarizes the milestones in the development of satralizumab leading to this first approval for the treatment of NMOSD.

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BACKGROUND: Satralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder (NMOSD), based on positive results from two randomized, double-blind, phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). There remains an unmet need to understand the real-world management of NMOSD, especially in patients undergoing tapering of concomitant therapy. We examined real-world treatment patterns, including concomitant glucocorticoids and immunosuppressants, and relapse in satralizumab-treated patients with NMOSD, using a Japanese administrative hospital claims database. METHODS: We used retrospective data from the Medical Data Vision hospital-based administrative claims database. The index date was the date of first satralizumab prescription and the study period was set between August 2018 and March 2022. Patients were included in the overall population if they had a first prescription for satralizumab between August 2020 and March 2022, an International Classification of Disease, Version10 code of G36.0 prior to March 2022, and were observable for ≥90 days prior to the index date. The primary endpoint was the percentage of patients with relapse-free reduction of oral glucocorticoids to 0 mg/day at 360 days of continued satralizumab treatment. Secondary endpoints included time to relapse, number of relapses after the index date while being on continuous satralizumab treatment, annualized relapse rate before and after the index date, and concomitant medication use. Relapse and dose reduction were identified using definition specifically developed for this study. RESULTS: Of the 131 patients included in the overall population, most were female (90.8 %), aged 18-65 years (75.6 %), and were prescribed oral glucocorticoids (93.1 %). Azathioprine (19.1 %) and tacrolimus, a calcineurin inhibitor (18.3 %), were the most common immunosuppressants at index date. Six (4.6 %) patients had a history of biologic use (tocilizumab, 1 [0.8 %]; eculizumab, 5 [3.8 %]). Among 111 patients observable for 360 days pre-index, there were 0.6 ± 0.8 (mean ± SD) relapses during 360 days before the index date. The median (interquartile range) duration of satralizumab exposure was 197.0 (57.0-351.0) days. Most (125/131; 95.4 %) patients were relapse-free post-index; 6 (4.6 %) patients relapsed within 90 days after the index date, of which 2 had the first relapse within 7 days after the index date. Among 21 patients with 360-day follow-up, 6 (28.6 %) patients were on 0 mg/day dose of glucocorticoid prescription without relapse 360 days post-index. Of these 6 patients, 2 had no prescription of oral glucocorticoids at the index date and remained glucocorticoid- and relapse-free 360 days after the index date. CONCLUSION: These real-world data support the phase 3 clinical trials. Our results, over a median duration of satralizumab exposure of 197.0 days, showed that a majority (125/131, 95.4 %) of patients were relapse-free after initiating satralizumab treatment. The number of glucocorticoid-free patients without relapse increased over time under continuous satralizumab prescription. Further studies are needed to confirm if satralizumab can be used as a potential immunosuppressant- and glucocorticoid-sparing agent.

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Background: -methyl-d-aspartic acid receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) are the most common subtypes of antibody-positive AIE. Currently, there are no approved therapies for AIE. Interleukin-6 (IL-6) signaling plays a role in the pathophysiology of AIE. Satralizumab, a humanized, monoclonal recycling antibody that specifically targets the IL-6 receptor and inhibits IL-6 signaling, has demonstrated efficacy and safety in another autoantibody-mediated neuroinflammatory disease, aquaporin-4 immunoglobulin G antibody-positive neuromyelitis optica spectrum disorder, and has the potential to be an evidence-based disease modifying treatment in AIE. Objectives: CIELO will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of satralizumab compared with placebo in patients with NMDAR-immunoglobulin G antibody-positive (IgG+) or LGI1-IgG+ AIE. Study design: CIELO (NCT05503264) is a prospective, Phase 3, randomized, double-blind, multicenter, basket study that will enroll approximately 152 participants with NMDAR-IgG+ or LGI1-IgG+ AIE. Prior to enrollment, participants will have received acute first-line therapy. Part 1 of the study will consist of a 52-week primary treatment period, where participants will receive subcutaneous placebo or satralizumab at Weeks 0, 2, 4, and every 4 weeks thereafter. Participants may continue to receive background immunosuppressive therapy, symptomatic treatment, and rescue therapy throughout the study. Following Part 1, participants can enter an optional extension period (Part 2) to continue the randomized, double-blind study drug, start open-label satralizumab, or stop study treatment and continue with follow-up assessments. Endpoints: The primary efficacy endpoint is the proportion of participants with a ≥1-point improvement in the modified Rankin Scale (mRS) score from study baseline and no use of rescue therapy at Week 24. Secondary efficacy assessments include mRS, Clinical Assessment Scale of Autoimmune Encephalitis (CASE), time to rescue therapy, sustained seizure cessation and no rescue therapy, Montreal Cognitive Assessment, and Rey Auditory Verbal Learning Test (RAVLT) measures. Safety, pharmacokinetics, pharmacodynamics, exploratory efficacy, and biomarker endpoints will be captured. Conclusion: The innovative basket study design of CIELO offers the opportunity to yield prospective, robust evidence, which may contribute to the development of evidence-based treatment recommendations for satralizumab in AIE.

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INTRODUCTION: Satralizumab, an anti-interleukin-6 receptor antibody, is approved in Japan for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and is undergoing post-marketing surveillance (PMS) of clinical use. We aimed to describe the real-world safety and effectiveness of satralizumab in Japanese patients with NMOSD. METHODS: This is an ongoing PMS (planned completion: February 2027). This 6-month interim analysis assessed the safety and effectiveness of satralizumab in Japanese patients with NMOSD using data collected from August 2020 to July 2021. RESULTS: Among 570 patients who participated, 523 (91.75%) were female and the mean ± standard deviation (SD) age was 52.4 ± 14.1 years. At baseline, NMOSD expanded disability status scale mean ± SD was 4.19 ± 2.19; 490 (85.96%) patients used glucocorticoids and 277 (48.59%) patients used immunosuppressants concomitantly. Of 570 satralizumab-treated patients, 85 (14.91%) had discontinued satralizumab treatment at 6 months. For the overall adverse drug reactions (ADRs), 76.22 (66.07-87.48) events/100 person-years occurred in 118 (20.70%) patients, and infections occurred in 28 (4.91%) patients. Serious infections occurred in 18 (3.15%) patients, with an event rate of 9.05 (5.80-13.47) events/100 person-years. Of the 24 events of serious infections, respiratory tract infections (29.17%; 7) and urinary tract infections (25.00%; 6) were the most common serious infection events. One fatal ADR (septic shock) suspected to be related to satralizumab was reported. The mean ± SD glucocorticoid dose reduced from 12.28 ± 10.17 mg/day at the index date to 8.11 ± 7.30 mg/day at 6 months. The Kaplan-Meier cumulative relapse-free rate (95% confidence interval) was 94.59% (92.25-96.23) at 6 months. CONCLUSION: In this study, satralizumab was found to be safe, well tolerated, and effective in patients with NMOSD in routine clinical practice. The results are consistent with those of previous clinical trials. The safety and effectiveness of satralizumab in Japanese patients with NMOSD will be analyzed over the 6-year surveillance period. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000041047.

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