Satralizumab: First Approval

Heo, Young-A

doi:10.1007/s40265-020-01380-2

Cited by 49 publications

(34 citation statements)

References 18 publications

(45 reference statements)

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“…Canada also approved subcutaneous Satralizumab for the treatment of NMOSD in adults and children aged ≥ 12 years with AQP-4 seropositivity. 31 While Tocilizumab is still used off-label in some case studies and in clinical studies. Tocilizumab, however, is considered a safe and effective alternative to azathioprine in controlling relapses with the need for further trials.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis

Kharel

Shrestha

Ojha

et al. 2021

Preprint

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BackgroundInterleukin-6 (IL-6) inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various IL-6 inhibitors in the management of NMO/NMOSD.MethodsPubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients, on trial relapse risk, and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS-before and after treatment. While pooled risk ratio between the intervention group and placebo group was used in Randomized Controlled Trial (RCTs). A forest plot was prepared to indicate the efficacy outcomes.Results A total of nine studies with 202 patients were included in our meta-analysis. IL-6 inhibitors found a good proportion (75%,95% CI: 0.62–0.89; p<0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6 95% CI: -2.71 to -1.68; p<0.001) and on trial relapse risk (RR: 0.46; 95% CI: 0.32‐0.66; P< 0.001) but did not show significant difference in change in EDSS score (mean difference=-0.79, 95% CI: -1.89 to -0.31; p=0.16). Also, the toxicity profile of IL-6 inhibitors was acceptable considering the proportions of patients with adverse events (72%, 95% C.I.;0.59-0.84, I2=85.29%, p<0.001), proportions of patients with serious adverse events (18%;95% C.I.; -3.68 to 4.04, I2=0%, p=0.93) and zero treatment related deaths. In subgroup analysis, we found subcutaneous administration to be superior (81%;95% CI:0.74-0.82) than intravenous route (67%; 95% CI:0.67-0.89) in relapse free maintenance.ConclusionIL-6 inhibitor therapy showed significant benefits in reducing mean ARR, relapse risk and increasing the number of relapse-free patients with acceptable adverse events profile.

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Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis

Kharel

Shrestha

Ojha

et al. 2021

Preprint

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“…This feature enabled the release from membrane-bound IL-6R in the endosome, eventually leading to a 20-fold increase in the antibody concentration in blood plasma after 78 h. Moreover, the soluble form of IL-6R was reduced 40-fold with the acid-switched antibody compared to the non-pH-sensitive antibody at day 4. This anti-IL-6R recycling antibody, under the name of satralizumab, 49 and ravulizumab, 50 an acid-sensitive antibody against the complement component C5, have recently been approved for their use in clinics. The first is used to treat neuromyelitis optica and the latter for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.…”

Section: Ph Activationmentioning

confidence: 99%

The Masking Game: Design of Activatable Antibodies and Mimetics for Selective Therapeutics and Cell Control

2021

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The high selectivity and affinity of antibody binding have made antibodies all-pervasive tools in therapy, diagnosis, and basic science. A plethora of chemogenetic approaches has been devised to make antibodies responsive to stimuli ranging from light to enzymatic activity, temperature, pH, ions, and effector molecules. Within a single decade, the field of activatable antibodies has yielded marketed therapeutics capable of engaging antigens that could not be targeted with traditional antibodies, as well as new tools to control intracellular protein location and investigate biological processes. Many opportunities remain untapped, waiting for more efficient and generally applicable masking strategies to be developed at the interface between chemistry and biotechnology.

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“…The potent ability of recycling antibodies to clear soluble Ag can therefore be attributed to their intracellular unbinding of Ag, endosomal binding to FcRn, and subsequent exocytosis, rather than their affinity for Ag alone; moreover, these trafficking pathways have been confirmed by microscopy studies [ 157 ]. Of all the recycling antibodies under development, satralizumab became the first recycling antibody to receive commercial approval by the U.S. Food and Drug Administration (FDA) and is indicated for neuromyelitis optica spectrum disorder [ 158 ]. Recycling antibodies have since been investigated against other soluble targets including PCSK9, C5, and CXCL10 [ 156 , 159 , 160 , 161 ].…”

Section: Fcrn Effects On Monoclonal Antibody Pharmacokineticsmentioning

confidence: 99%

In Translation: FcRn across the Therapeutic Spectrum

Cao

2021

IJMS

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As an essential modulator of IgG disposition, the neonatal Fc receptor (FcRn) governs the pharmacokinetics and functions many therapeutic modalities. In this review, we thoroughly reexamine the hitherto elucidated biological and thermodynamic properties of FcRn to provide context for our assessment of more recent advances, which covers antigen-binding fragment (Fab) determinants of FcRn affinity, transgenic preclinical models, and FcRn targeting as an immune-complex (IC)-clearing strategy. We further comment on therapeutic antibodies authorized for treating SARS-CoV-2 (bamlanivimab, casirivimab, and imdevimab) and evaluate their potential to saturate FcRn-mediated recycling. Finally, we discuss modeling and simulation studies that probe the quantitative relationship between in vivo IgG persistence and in vitro FcRn binding, emphasizing the importance of endosomal transit parameters.

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Satralizumab: First Approval

Cited by 49 publications

References 18 publications

Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis

Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis

The Masking Game: Design of Activatable Antibodies and Mimetics for Selective Therapeutics and Cell Control

In Translation: FcRn across the Therapeutic Spectrum

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