欧盟批准强生单抗药Sylvant（siltuximab）

欧盟批准强生单抗药Sylvant（siltuximab）

                               
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发布日期：2014-06-10  来源：新药汇  
强生单抗药物Sylvant获欧盟批准，用于HIV阴性和HHV-8阴性的多中心型巨大淋巴结增生症（MCD）的治疗。Sylvant是欧盟批准的首个MCD药物，已于2014年4月获FDA批准。

强生（JNJ）旗下杨森-Cilag国际（Janssen-Cilag International）近日宣布，欧盟委员会（EC）已批准单抗药物Sylvant（siltuximab），用于HIV阴性和人类疱疹病毒-8（HHV-8）阴性的多中心型巨大淋巴结增生症（multicentric Castleman'sdisease，MCD）患者的治疗。Sylvant是欧盟批准的首个MCD治疗药物。
Sylvant是一种单克隆抗体，是IL-6拮抗剂，通过静脉输注给药，每3周一次，该药已于2014年4月获FDA批准用于相同适应症，也是FDA批准的首个MCD治疗药物。Sylvant通过靶向白介素6（IL-6）发挥作用，IL-6似乎是MCD的关键驱动因子。
Sylvant的疗效和安全性，已在一项关键性III期研究（MCD2001）中得到证实。该研究是首个在MCD患者中开展的随机III期研究，评价了siltuximab+最佳支持治疗（BSC）相对于安慰剂+BSC治疗MCD患者的疗效和安全性。研究数据表明，siltuximab+BSC治疗组有显着更多的患者取得了持续的肿瘤和对症响应（肿瘤体积减少和疾病症状减轻）（34%vs0%，p=0.0012）。
多中心型巨大淋巴结增生症（MCD）是一种罕见疾病，是由于某种类型的白细胞过度生产导致淋巴结肿大。该病可能导致各种症状，并削弱免疫系统，使之难以对抗感染。对MCD患者而言，感染会非常严重甚至可能致命。目前，在美国和欧洲，还没有药物获批用于治疗这种罕见血液疾病。
强生于2013年9月向FDA和欧洲药品管理局（EMA）提交了siltuximab治疗MCD的生物制品许可申请（BLA）和上市许可申请（MAA），此前，FDA和EMA均已授予siltuximab治疗MCD的孤儿药地位。
关于Sylvant（siltuximab）：
siltuximab是一种实验性、抗白介素6（IL-6）嵌合单克隆抗体，靶向并结合人IL-6。IL-6是由多种细胞产生的一种多功能细胞因子，如T细胞、B细胞、单核细胞、成纤维细胞和内皮细胞。MCD疾病的发病机制，牵涉受影响的淋巴结中活化B细胞内IL-6的失调或不平衡过量生产。
英文原文：European Commission Approves SYLVANT® (siltuximab) as a Treatment for Patients with Multicentric Castleman's Disease (MCD)
First treatment approved for the management of MCD in Europe
Beerse / Belgium, June 4, 2014 - Janssen-Cilag International NV ("Janssen") announced today that the European Commission (EC) has approved the use of SYLVANT® (siltuximab) for the treatment of adult patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpes virus-8 (HHV-8) negative.1 SYLVANT is a monoclonal antibody (a specialised type of protein) that binds selectively to an antigen in the body called interleukin-6 (IL-6). SYLVANT is administered as an intravenous (IV) infusion once every three weeks2 and is the first medicine to receive regulatory approval in the EU for the treatment of MCD patients.
MCD is a rare blood disorder with high morbidity in which lymphocytes, a type of white blood cells, are over-produced, leading to enlarged lymph nodes. MCD can also affect lymphoid tissue of internal organs, causing the liver, spleen, or other organs to enlarge.3 Infections, multisystem organ failure and malignancies including malignant lymphoma are common causes of death in patients with MCD.3,4 It is classified as a rare disease by the European Commission, meaning that it affects fewer than five in 10,000 people.5 In fact, MCD is so rare that it is difficult to track the number of cases across Europe. As the majority of publications on MCD are based on case reports, epidemiological evidence is very scarce. However, a recent study from the U.S. estimated the 10-year prevalence of MCD to be 2.4 cases per million inhabitants.6
"The approval of SYLVANT means that there is now an EU approved treatment for patients with MCD who are HIV negative and HHV-8 negative. SYLVANT will provide an urgently needed treatment option that will make a significant difference to the way that MCD is managed," said Professor Pier Luigi Zinzani, Associate Professor of Hematology, University of Bologna, Italy. "It has the potential to become a new standard of care for patients, providing an important new therapeutic option to those suffering with this chronic, serious and debilitating disease."
While the cause of MCD currently is unknown, overproduction of IL-6 is considered a key mechanism in MCD.3,7 SYLVANT works by binding to human IL-6, a multifunctional cytokine produced by various cells such as T cells, B cells, monocytes, fibroblasts and endothelial cells.2,7
Jane Griffiths, Company Group Chairman of Janssen Europe, the Middle East and Africa (EMEA) said, "Janssen is committed to developing compounds in areas of unmet medical need and our expertise in haematologic malignancies was key to recognising the potential of SYLVANT. As the first company with an approved medicine to treat MCD in Europe, we are very proud to be able to offer an effective treatment option for eligible patients with this rare and challenging disease and further demonstrate our commitment to patients."
The EC approval was based on the results of the MCD2001 Pivotal Study and follows the accelerated assessment and recommendation from the CHMP to approve SYLVANT® on March 20, 2014. The U.S. Food and Drug Administration's approval of SYLVANT™ was announced on April 23, 2014. SYLVANT has been granted orphan drug status for MCD in both the EU and the United States (U.S.).
about the study
The efficacy and safety of SYLVANT were evaluated in a multi-national, randomised, double-blind, placebo-controlled pivotal study in 79 patients with MCD (MCD2001). MCD2001 is the first randomised study in MCD.8 Fifty-three patients were randomised to the SYLVANT arm at a dose of 11 mg/kg every 3 weeks and 26 patients were randomised to the placebo arm. Patients had symptomatic MCD and were HIV negative and HHV-8 negative.2,8
Treatment of MCD tumours and related symptoms is an important treatment goal for these patients. In this pivotal study, which led to the European Commission approval, more than one-third of patients in the SYLVANT arm had a durable tumour and symptomatic response to treatment plus best supportive care (BSC), compared to none of the patients who received placebo plus BSC (34 percent versus 0 percent according to stringent criteria; 95 percent CI: 11.1, 54.8; p=0.0012). A durable response was defined as tumour and symptomatic response (reduction in tumour size and complete resolution or stabilisation of disease symptoms) that persisted for a minimum of 18 weeks without treatment failure. The median time to treatment failure was not reached for patients who received SYLVANT plus BSC; those who received placebo plus BSC experienced treatment failure at a median of 134 days (p=0.0084). Efficacy results from MCD2001 also showed tumor response for those in the SYLVANT arm was 37.7 percent versus 3.8 percent for those in the placebo arm (p=0.0022). Among anaemic patients, an increase in hemoglobin of at least 15 g/L at week 13 was seen in 61.3 percent of patients in the SYLVANT arm versus 0 percent in patients who received placebo and BSC (p=0.0002).2,8 (Note. SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because it did not bind to virally produced interleukin-6 (IL-6) in a nonclinical study.)
about SYLVANT® (siltuximab)
SYLVANT is an anti-interleukin-6 (IL-6) chimeric monoclonal antibody that binds to human IL-6.2 IL-6 is a multifunctional cytokine produced by various cells such as T cells, B cells, monocytes, fibroblasts and endothelial cells. Dysregulated overproduction of IL-6 from activated B cells in affected lymph nodes has been implicated in the pathogenesis of, or mechanism causing, MCD.7 Information about ongoing studies with siltuximab can be found at www.clinicaltrials.gov.
about multicentric Castleman's disease (MCD)
MCD is a rare blood disorder with high morbidity in which lymphocytes, a type of white blood cell, are over-produced and lead to enlargement of lymph nodes. MCD can also affect lymphoid tissue of internal organs, causing the liver, spleen or other organs to enlarge.3 MCD signs and symptoms are driven by dysregulated IL-6 production.3,7 Some symptoms can be life threatening.3,4
Unlike "unicentric" Castleman's disease, which is localised and affects only a single area or group of lymph nodes, patients with MCD have more than one group of lymph nodes in different anatomical areas that are affected. Unicentric disease can be treated by surgically removing the diseased lymph node, while multicentric disease is usually much more difficult to treat.