强生单抗药Sylvant获FDA批准

关键词:单抗药,强生,Sylvant,siltuximab,多中心巨大淋巴结增生症,孤儿药

2014年4月24日讯 /生物谷BIOON/ --强生(JNJ)旗下杨森研发单元(Janssen)4月23日宣布,FDA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's disease,MCD)患者的治疗。此前,siltuximab已被授予孤儿药地位。

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治疗组有显著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% vs 0%,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。(生物谷Bioon.com)

英文原文:SYLVANT™ (siltuximab) Receives FDA Approval to Treat Multicentric Castleman's Disease (MCD)

First treatment approved for patients with rare blood disorder

HORSHAM, Pa., April 23, 2014 /PRNewswire/ -- Janssen Biotech, Inc. ["Janssen"] today announced the U.S. Food and Drug Administration (FDA) has approved SYLVANT™ (siltuximab) for the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced interleukin-6 (IL-6) in a nonclinical study. SYLVANT is an IL-6 antagonist biologic therapy administered as an intravenous (IV) infusion once every three weeks.1  SYLVANT is the first approved treatment in the U.S. for MCD.

MCD is a rare blood disorder with high morbidity in which lymphocytes, a type of white blood cell, 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.2 Infections, multisystem organ failure and malignancies including malignant lymphoma are common causes of death in patients with MCD.2,3,4,5

"There has been a serious need for treatment options for patients with MCD," said Frits van Rhee, M.D., Ph.D., University of Arkansas for Medical Sciences, and MCD2001 study lead investigator. "MCD is a complex disease and up until this point, physicians have tried to reduce lymph node masses and put the disease in remission through a combination of treatments, but MCD often returns.Today's approval of SYLVANT gives physicians a long-awaited treatment option for a group of patients who has been suffering with this chronic, serious and debilitating disease."

MCD is a proliferative disease that acts very much like lymphoma (cancer of lymph nodes). It is so rare that it is difficult to track the number of cases,2 though a recent U.S. analysis estimates* the incidence of MCD at approximately 1,100 to 1,300 Americans.6

"Today's approval of a treatment for patients with multicentric Castleman's disease marks a significant milestone for patients living with this rare disease and underscores the importance of ongoing research and development in areas where there are so few patients with such a high unmet medical need," said Peter L. Saltonstall, president and CEO, National Organization of Rare Disorders (NORD), a federation of health organizations dedicated to helping people with rare diseases.

While the cause of MCD currently is unknown, overproduction of IL-6 is considered a key mechanism in MCD.2,7 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.1,7

"SYLVANT exemplifies Janssen's approach to research and development, as well as our commitment to patients," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen. "Our expertise in hematologic malignancies was key to recognizing the potential for SYLVANT in this rare disease. We're extremely proud to be the first company with an approved medicine to treat MCD in the U.S."

About the MCD2001 Pivotal Study The efficacy and safety of SYLVANT were evaluated in a multi-national, randomized, double-blind, placebo-controlled pivotal study in 79 patients with MCD (MCD2001). MCD2001 is the first randomized study in MCD.8 Fifty-three patients were randomized to the SYLVANT arm at a dose of 11 mg/kg and 26 patients were randomized to the placebo arm. Patients had symptomatic MCD and were HIV negative and HHV-8 negative.1

Treatment of MCD tumors and related symptoms is an important treatment goal for these patients. In this pivotal study, which led to the FDA approval, more than one-third of patients in the SYLVANT arm had a durable tumor 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; 95 percent CI: 11.1, 54.8; p=0.0012). A durable response was defined as tumor and symptomatic response (reduction in tumor size and 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<0.05). Efficacy results from MCD2001 also showed tumor response for those in the SYLVANT arm was 38 percent versus four percent for those in the placebo arm (p<0.05). Among anemic patients, an increase in hemoglobin of 1.5 g/dL was seen in 61 percent of patients in the SYLVANT arm versus 0 percent in patients who received placebo and BSC (p<0.05).

The warnings and precautions for SYLVANT include concurrent active severe infections, administration of live vaccines, infusion related reactions and hypersensitivity and gastrointestinal perforation.1 For more information about warnings and precautions, please see below in this press release.

The most frequent adverse reactions (greater than 10 percent compared to placebo) during treatment with SYLVANT in the MCD clinical trial were rash (28 percent), pruritus (itching) (28 percent), upper respiratory tract infection (26 percent), increased weight (19 percent) and hyperuricemia (high uric acid level) (11 percent).1

*Estimate from a U.S. claims database

Access to SYLVANT Janssen Biotech is committed to helping patients obtain access to our medicines by offering comprehensive access services and support for patients. The SylvantOne™ Support program offers a variety of services for providers and patients that can help assess insurance coverage and identify cost support options, such as the SylvantOne™ Patient Rebate Program for eligible commercial patients, as well as a potential option for those who are uninsured. Patients and providers can contact SylvantOne™ Support by calling 1-855-299-8844.

About SYLVANT™ (siltuximab) SYLVANT is an anti-interleukin-6 (IL-6) chimeric monoclonal antibody that binds to human IL-6.1 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

On September 3, 2013, Janssen announced simultaneous submissions of a Biologic License Application (BLA) to the United States Food and Drug Administration (U.S. FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for siltuximab for the treatment of patients with MCD who are HIV negative and HHV-8 negative. The FDA granted the siltuximab BLA priority review in the U.S. and the EMA has granted Accelerated Assessment of the MAA. Siltuximab has been granted orphan drug status in MCD in the U.S. and European Union.

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.2 Signs and symptoms are driven by dysregulated IL-6 production.2,7 Common symptoms include enlarged lymph nodes (appearing as lumps under the skin), fever, weakness, fatigue, night sweats, weight loss, loss of appetite, nausea, vomiting and nerve damage that leads to numbness and weakness.2 Some symptoms can be life threatening.Infections, multisystem organ failure and malignancies including malignant lymphoma are common causes of death in patients with MCD.2,3,4,5

Unlike "unicentric" Castleman's disease, which is localized and affects only a single area or group of lymph nodes,patients with MCD have

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