诺华单抗药物Ilaris获批用于SJIA

　　

　　2013年5月10日讯 /生物谷BIOON/ --诺华（Novartis）今天宣布，FDA已批准Ilaris（canakinumab）用于2岁及以上活动性全身型幼年特发性关节炎（SJIA）患者的治疗。Canakinumab是一种选择性、全人源化、抗-IL-1β单克隆抗体药物，是首个获批用于SJIA的IL-1β抑制剂，同时也是唯一获批专门用于SJIA治疗且每月仅需一次的皮下注射药物。

　　SJIA是一种罕见致残性的幼年关节炎，其特点是反复性的发烧、皮疹及关节炎症，该病可影响仅2岁的儿童，并可持续至成年。

　　Ilaris的获批，是基于在2~19岁SJIA患者中开展的2项III期临床试验，结果表明Ilaris治疗组中大多数患者取得了显着性改善。

　　Study 1表明，经一个皮下剂量治疗后，Ilaris治疗组在第15天（Day-15）有84%的患者达到了ACR30的主要终点，而安慰剂组仅为10%。Study 2开放标签研究部分，128例患者中有92例尝试了皮质类固醇减少试验，这92例患者中有62%能够大大降低其糖皮质激素的使用，46%的患者能够完全停用糖皮质激素。Study 2对照研究部分中，Ilaris治疗组耀斑（flare）风险比安慰剂组低64%（风险比为0.36，95％CI：0.17?0.75）。

　　Ilaris是一种选择性、全人源化的单克隆抗体，靶向抑制白介素-1β（IL-1β）。IL-1β是人体免疫系统防御的重要组成部分。在某些炎症性疾病中，IL-1β的过度产生发挥了突出的作用。Ilaris能够中和IL-1β，从而抑制炎症反应。

　　除了在美国获批用于SJIA之外，Ilaris已获欧盟批准用于难治性痛风性关节炎，并在超过60个国家和地区（包括欧盟、美国、瑞士、日本等）获批用于冷吡啉相关周期性综合征(Cryopyrin-Associated Periodic Syndromes，CAPS)，该病是一种罕见的致命性的自体发炎性疾病。（生物谷bioon.com）

　　英文原文：Novartis drug Ilaris approved by FDA to treat active systemic juvenile idiopathic arthritis, a serious form of childhood arthritis

　　Ilaris? (canakinumab) is the first interleukin-1 beta inhibitor for the treatment of SJIA and the only treatment approved specifically for SJIA that is given as a monthly subcutaneous injection[1]

　　In Phase III studies, 84% of Ilaris-treated SJIA patients achieved significant improvement of systemic and arthritic symptoms (pediatric ACR30) after a single subcutaneous dose[1]

　　SJIA is a rare, disabling autoinflammatory disease with limited treatment options[2]; Ilaris is being investigated in other inflammatory conditions, including several rare diseases for which approved treatment options do not exist

　　Basel, May 10, 2013 - Novartis announced today that the US Food and Drug Administration (FDA) has approved Ilaris? (canakinumab) for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older. Ilaris is the first interleukin-1 beta (IL-1 beta) inhibitor approved for SJIA and the only treatment approved specifically for SJIA that is given as a once-monthly subcutaneous injection[1]. SJIA is a rare and disabling form of childhood arthritis characterized by spiking fever, rash and arthritis that can affect children as young as 2 years old and can continue into adulthood[2],[3].

　　This approval was based on two Phase III trials in SJIA patients, aged 2-19, showing significant improvement in the majority of Ilaris-treated patients[1]. Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 (ACR30), compared to 10% achievement of ACR30 for placebo at Day 15[1]. In the open-label part of Study 2, 92 of 128 patients attempted "corticosteroid tapering". Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids[1]. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group (hazard ratio of 0.36; 95% CI: 0.17 to 0.75).

　　"In the US, this approval marks the second Ilaris indication for patients living with rare, autoinflammatory conditions," said Timothy Wright, MD, Global Head of Development, Novartis Pharmaceuticals. "We are committed to studying Ilaris in other IL-1 beta mediated inflammatory diseases, including several rare diseases for which treatment options do not currently exist."

　　SJIA affects 5-15 children per 100,000 in the United States,and is the most severe subtype of juvenile idiopathic arthritis[3]-[5]. Although the disease can be life-threatening, treatment options are limited. Corticosteroids are often used to treat symptoms and pain despite their long term use being associated with potentially serious adverse effects, including Cushing syndrome, growth suppression and osteoporosis[1],[6],[7].

　　Ilaris is being investigated in a number of rare autoinflammatory conditions, including Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), colchicine-resistant Familial Mediterranean Fever (FMF) and Hyper IgD Syndrome (HIDS). Ilaris is considered an investigational agent for these conditions at this point in time. As such, the role that Ilaris could play in treating these conditions and potential benefit to patients is still being determined.

　　About the Pivotal Phase III Studies

　　Study 1, a 4-week, randomized, double-blind, placebo-controlled study, involved 84 patients between the ages of 2 and 19 years with active SJIA[1],[2]. Patients were treated with either a single subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) (n=43) or placebo (n=41)[1]. The primary endpoint was the proportion of patients achieving the adapted pediatric American College of Rheumatology (ACR) 30 response criteria and resolution of fever from baseline at Day 15[1]. This means that patients had at least a 30% improvement in systemic and arthritic symptoms versus baseline. The study met its primary endpoint.

　　Study 2, a two-part study, had an open-label, single-arm active treatment in Part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in Part II[1]. A total of 177 patients between the ages of 2 and 19 years with active SJIA were enrolled in the study[1]. Some of these patients had previously participated in the Study 1. In Part I, patients received a subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) every 4 weeks[1]. The primary endpoint of Part I was to assess whether treatment with Ilaris allowed successful tapering of corticosteroids in at least 25% of SJIA patients who entered the study using a corticosteroid.

　　In Part II of the study, patients were randomized to either continue receiving Ilaris, or to receive placebo every 4 weeks ("placebo-after-Ilaris group"), until a pre-specified number (37) of flare-events ("flares") had occurred[1]. The primary endpoint of Part II was to demonstrate that the time to flare was longer with Ilaris than with placebo.

　　The primary endpoints for Study 1 and Study 2 were all met.

　　About Ilaris

　　Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body's immune system defenses[1]. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases[8]. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation[1].

　　In addition to its approval for SJIA in the US, Ilaris is approved in the EU for the treatment of refractory gouty arthritis, and in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a rare, lifelong, genetic disorder with debilitating symptoms[1]. The approved indication may vary depending upon the individual country.