The exact mechanisms of action of satralizumab in treating NMOSD is currently unknown, but is thought to target multiple aspects that contribute to the disease in patients with NMOSD by binding to membrane-bound and soluble IL-6 receptors, thereby blocking IL-6 signalling pathways [6, 10, 16]. ?12 years with NMOSD who are AQP4-IgG seropositive Open in a separate window Introduction Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system (CNS) that is characterized by inflammatory and demyelinating lesions in optic nerve, spinal cord brainstem and cerebrum, which can lead to progressive impairment of vision and motor functions [1C4]. The primary goal of NMOSD treatment is to reduce the risk of irreversible neurological impairment by preventing relapse and reducing the severity of attacks [5, 6]. Recent research suggested that interleukin-6 (IL-6) has an important role in the immunopathogenesis of NMOSD [1, 2]. IL-6 signalling triggers an inflammatory cascade that is thought to lead to differentiation of T cells into proinflammatory TH17 cells, differentiation of B cells into plasmablasts that produce aquaporin 4 water channel autoantibodies (AQP4-IgG), Rabbit polyclonal to HDAC6 a diagnostic serum marker that is found in ?80% of patients with NMOSD, and an increase in bloodCbrain barrier (BBB) permeability, allowing penetration of antibodies and proinflammatory cells into the CNS [2, 7C10]. Satralizumab (Enspryng?), a humanized anti-IL-6 receptor monoclonal antibody designed using recycling antibody technology?, has been developed by Chugai Pharmaceutical and Roche for the treatment of NMOSD [11]. Based on positive results from two pivotal phase III trials, satralizumab received its first global approval under priority review in Canada on 1 June 2020 for the Pomalidomide-C2-NH2 treatment of NMOSD as monotherapy or as combination therapy with immunosuppressant in adults and children aged ?12 years who are AQP4-IgG seropositive [11]. On 29 June 2020, satralizumab was subsequently approved in Japan for the prevention of relapses of NMOSD, including neuromyelitis optica (NMO), in adults and children who are AQP4-IgG seropositive [12]. On 13 July 2020, satralizumab was approved in Switzerland for the treatment of NMOSD as monotherapy or as combination therapy with immunosuppressant in adults and adolescents who are AQP4-IgG seropositive [13]. On 17 August 2020, satralizumab was approved in the USA for the treatment of NMOSD in adult patients who are AQP4 antibody positive [14, 15]. Open in a separate window Key milestones in the development of satralizumab Biologics License Application, Marketing Authorization Application, neuromyelitis optica, neuromyelitis optica spectrum disorder Satralizumab is available as a single-use, prefilled syringe containing 120 mg/mL satralizumab for subcutaneous injection and the recommended dosage is 120 mg at week 0, 2 and 4 as loading doses, followed by a maintenance dose of 120 mg every 4 weeks [13, 15C17]. Pomalidomide-C2-NH2 The first subcutaneous injection of satralizumab should be administered under supervision of a health practitioner. During satralizumab treatment, liver enzyme levels should be monitored every 4 weeks for the first 3 months, followed by every 3 months for 1 year; neutrophil counts should be monitored 4C8 weeks after treatment initiation and as clinically indicated thereafter [13, 15C17]. Subcutaneous satralizumab is under regulatory review in the EU [18, 19], and is undergoing clinical development in several countries worldwide. Pomalidomide-C2-NH2 In Japan, phase I clinical development was conducted for the treatment of rheumatoid arthritis; however, no recent development reports Pomalidomide-C2-NH2 have been identified. Company Agreements In June 2016, Chugai Pharmaceutical and Roche entered into an exclusive worldwide license agreement under which the latter was granted the worldwide rights for the development and marketing of satralizumab, with the exception of Japan and Taiwan [20, 21]. Under the terms of the agreement, Chugai is entitled to receive an upfront fee, milestone and royalty payments from Roche, while being responsible for continued product manufacturing and supply of satralizumab [20]. Scientific Summary Pharmacodynamics Satralizumab is a humanized immunoglobulin G2 monoclonal antibody produced in Chinese hamster ovary cells using recombinant DNA technology [16]. The exact mechanisms of action of satralizumab in treating NMOSD is currently unknown, but is thought to target multiple aspects that contribute to the disease in patients with NMOSD by binding to membrane-bound and soluble IL-6 receptors, thereby blocking IL-6 signalling pathways [6, 10, 16]. Through inhibition of downstream IL-6 signalling.