2014年6月10日，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。
Sylvant(Siltuximab Injection, for Intravenous Infusion)
Generic Name: siltuximab (sil TUX i mab)
Brand Name: Sylvant
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS – Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT®.
Concurrent Active Severe Infections – Do not administer to patients with severe infections until the infection resolves. SYLVANT® may mask signs and symptoms of acute inflammation including suppression of fever and of acute phase reactants such as C-reactive protein (CRP). Monitor patients closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT® until the infection resolves.
Vaccinations – Do not administer live vaccines to patients receiving SYLVANT® because interleukin-6 (IL-6) inhibition may interfere with the normal immune response to new antigens.
Infusion Related Reactions and Hypersensitivity – Stop the infusion if the patient develops signs of anaphylaxis. Discontinue further therapy.
Stop the infusion if the patient develops mild to moderate infusion reactions. If the reaction resolves, the infusion may be restarted at a lower infusion rate. Consider medicating with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT® if the patient does not tolerate the infusion following these interventions.
Administer SYLVANT® in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.
Gastrointestinal (GI) Perforation – Use with caution in patients who may be at increased risk for GI perforation. Promptly eva luate patients presenting with symptoms that may be associated with or suggestive of GI perforation.
Adverse Reactions – The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.
Drug Interactions – Cytochrome P450 (CYP450) Substrates – Upon initiation or discontinuation of SYLVANT®, in patients being treated with CYP450 substrates with narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. Exercise caution when SYLVANT® is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).
INDICATION
SYLVANT® (siltuximab) is indicated 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.
Limitation of Use. SYLVANT® was not studied in patients with MCD who are HIV-positive or HHV-8 positive because SYLVANT® did not bind to virally produced IL-6 in a nonclinical study. |
