New drugs for rare diseases! The risk of recurrence was significantly reduced in the treatment of stage 3 of nmosd with rostralizumab!

November 30, 2019 / BIOON / -- Chugai, a Japanese pharmaceutical company controlled by Roche, recently announced the evaluation of McAbs Sakurasky (nct02028884), a global phase III clinical study of satralizumab (development code: sa237) in the treatment of neuromyelitis pedigree disorder (nmosd), has been published online in the international top medical journal NEJM The results showed that satralizumab combined with immunosuppressive therapy could significantly reduce the risk of relapse in patients with nmosd, and the combination therapy showed good tolerance and safety Satralizumab is a kind of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) In the United States, the FDA granted satralizumab a breakthrough drug qualification for the treatment of nmosd in December 2018 In the United States, the European Union and Japan, satralizumab has also been granted orphan drug qualification Satralizumab's regulatory application documents are based on the data of two global phase III clinical studies (sakurastar study, sakurasky study) The results confirm the efficacy and safety of satralizumab as a single drug therapy and combined therapy with baseline immunosuppressant, respectively The sakurasky study, published in NEJM, is a global, multicenter, randomized, double-blind, placebo-controlled phase III study involving 83 patients with nmosd and evaluating the efficacy and safety of satralizumab added to the baseline therapy In the study, patients were randomly assigned in a 1:1 ratio to two treatment groups: satralizumab (120 mg) or placebo added to the baseline therapy (azathioprine, mycophenolate mofetil and / or glucocorticoid) Satralizumab and placebo were injected subcutaneously at 0, 2 and 4 weeks, and the follow-up treatment was once every 4 weeks When the total number of relapses defined by the protocol is reached, the double-blind period ends After that, the patients in the two treatment groups entered the open label extension period and could continue to receive satralizumab treatment The results showed that: (1) compared with placebo + baseline immunosuppression therapy, satralizumab + baseline immunosuppression therapy significantly reduced the recurrence risk of nmosd patients (including AQP4 antibody positive and negative patients) by 62% (HR = 0.38 [95% CI: 0.16-0.88], P = 0.02), reaching the primary end point of the first protocol defined recurrence (PDR) time in double-blind period (2) At the 48th, 96th and 144th week, the proportion of relapse free patients in satralizumab group was 89%, 78% and 74% respectively, and that in placebo group was 66%, 59% and 49% respectively (3) The pre-defined subgroup analysis showed that satralizumab significantly reduced PDR risk by 79% (HR = 0.21 [95% CI: 0.06-0.75]) in AQP4 antibody positive subgroup (n = 55) compared with placebo, and 34% (HR = 0.66 [95% CI: 0.20-2.24]) in AQP4 antibody negative subgroup compared with placebo Overall, the proportion of patients with serious adverse events in the satralizumab treatment group and placebo group was similar in this study The infection rate (including severe infection) in the satralizumab group was lower than that in the placebo group The most common adverse reactions were upper respiratory tract infection, nasopharyngitis (common cold) and headache Soliris: the first nmosd treatment drug, nmosd, is a rare, life-long, aging autoimmune disease characterized by inflammatory lesions of the optic nerve and spinal cord Nmosd patients often experience recurrent disease process, recurrent attacks lead to gradual accumulation of nerve injury and disability, symptoms include vision disorders, motor disorders and quality of life decline In some cases, nmosd attacks can cause death Nmosd is usually associated with pathogenic antibodies (aquaporin-4 [AQP4] - IgG) AQP4 IgG targets and damages a specific cell type called astrocytes, resulting in inflammatory damage to the optic nerve, spinal cord and brain Through diagnostic biomarker testing, most nmosd patients were identified as AQP4 IgG seropositive; however, as many as one third of nmosd patients were AQP4 IgG seronegative This condition is often misdiagnosed as multiple sclerosis Satralizumab is a humanized monoclonal antibody targeting IL-6 receptor to inhibit IL-6 signaling IL-6 is a cytokine, which is considered to play a key role in the inflammation of nmosd, triggering the inflammatory cascade, leading to injury and disability Nmosd patients will experience unpredictable severe recurrence, which directly leads to cumulative and permanent neurological damage It is worth mentioning that, at the end of June this year, the rare disease giant alexion's first complement inhibitor, soliris (eculizumab), was approved by the US FDA for use in adult patients with neuromyelitis pedigree disorder (nmosd) with positive AQP4 antibody At the end of August this year, soliris was approved by the European Union for use in adult nmosd patients with AQP4 antibody positive and recurrent disease course In the United States and the European Union, soliris is the first and only drug approved to treat nmosd Results from phase III sakurasky study for Chugai's satralizumab in neuromelis optica spectrum disorder published in the New England Journal of Medicine Online