诺华（Novartis）近日宣布，单抗药物AIN457 (secukinumab)强直性脊柱炎2个关键III期研究（MEASURE-1，MEASURE-2）中均达到了主要终点和关键次要终点。这2个研究在近600例活动性强直性脊柱炎（AS）患者中开展，数据表明，与安慰剂相比，secukinumab显著改善了疾病的症状和体征，同时也显著改善了患者的身体机能和生活质量。该研究成果也标志着secukinumab成为首个在强制性关节炎（AS）III期临床获得成功的IL-17A阻断剂。这2项研究中，secukinumab的安全性与该药在银屑病大型III期项目中的安全性一致。研究的详细数据将提交至即将到来的医学会议。
secukinumab是一种实验性全人源化IgG1单抗，可特异性结合IL-17A，通过阻断IL-17A发挥作用。IL-17A是一种关键的促炎性细胞因子，在多种炎症性疾病的形成中至关重要，其中包括强直性脊柱炎（AS）。
诺华已计划在2015年提交secukinumab治疗银屑病关节炎（PsA）和强直性脊柱炎（AS）的监管申请。此前，诺华已于2013年10月提交了secukinumab治疗中度至重度斑块型银屑病（plaque psoriasis）的监管申请，预计将于2014年底或2015年初获批。
本周，FDA皮肤科和眼科药物顾问委员会（DODAC）一致投票支持批准secukinumab用于斑块型银屑病（plaque psoriasis）的治疗。该积极建议，是基于10个II/III期临床研究的数据，涉及近4000例中度至重度斑块型银屑病患者。FDA通常都会采纳顾问委员会的建议，这也意味着FDA将在2015年1月做出最终审查决定。
如果获批，secukinumab将成为市面上首个IL-17阻断剂药物。目前，银屑病市场由TNF阻断剂（抗肿瘤坏死因子单抗）统治，然而有高达40%的患者对TNF阻断剂治疗不足或无反应。而IL-17阻断剂的上市，将极大地改善银屑病、银屑病关节炎及其他炎症性疾病的临床标准护理。
有分析师认为，尽管诺华secukinumab很可能是上市的首个IL-17阻断剂，但该市场将很快迎来其他竞争产品。紧跟secukinumab之后的是安进和阿斯利康开发的类似药物brodalumab，该药在银屑病和银屑病关节炎III期临床中均创下了骄人的成绩。此外，礼来的IL-17阻断剂ixekizumab目前已进入III期临床，默沙东的MK-3222和强生（JNJ）的IL-23阻断剂guselkumab也将于本季度进入III期临床开发。
目前，诺华正在调查secukinumab用于多种炎症疾病的治疗，包括银屑病、银屑病关节炎、强直性脊柱炎（AS）和类风湿性关节炎（RA）。业界预测，如果这4个适应症均获批，secukinumab到2020年的销售额将突破10亿美元。
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英文原文：Novartis AIN457 (secukinumab) meets primary endpoint in two Phase III studies in ankylosing spondylitis, a debilitating joint condition of the spine
Secukinumab is the first selecive IL-17A inhibitor to meet primary endpoint in two pivotal Phase III studies showing improvement in active ankylosing spondylitis (AS) patients' symptoms versus placebo
AS is a painful, progressively debilitating condition associated with inflammation of the spine, causing irreversible consequences that significantly reduce patients' mobility and quality of life[1],[2]
Up to 40% of patients have an inadequate or no response to standard of care anti-TNF (tumor-necrosis-factor) medicines, currently the only biologic therapies available for patients with AS[1]
The secukinumab results in AS follow positive topline data in psoriatic arthritis (PsA) announced in September; joint regulatory filing of secukinumab in AS and PsA planned for 2015
basel, October 23, 2014 - Novartis today announced that AIN457 (secukinumab) met primary and key secondary endpoints in two pivotal Phase III studies (MEASURE 1 and MEASURE 2) in patients with ankylosing spondylitis (AS). Key endpoints included improvements in signs and symptoms of the disease versus placebo and associated improvements in physical function and quality of life. Secukinumab is an investigational medicine that works by stopping the action of interleukin-17A (IL-17A)[3], a protein that is central to the development of inflammatory diseases[4], including AS. MEASURE 1 and MEASURE 2 enrolled a combined total of approximately 600 patients. Detailed results of the studies will be presented at an upcoming medical congress.
"We are thrilled to see positive results with secukinumab in AS, a gravely debilitating condition with a significant remaining unmet need as up to 40% of patients do not respond to anti-TNF therapies," said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. "With these results in AS and the recently announced positive results in psoriatic arthritis, we now have data from four Phase III trials of secukinumab in spondyloarthropathies which we look forward to presenting at a congress later this year."
AS is a common type of spondyloarthropathy (SpA), a family of long-term diseases impacting joints (inflammatory diseases), which includes other conditions such as psoriatic arthritis (PsA)[5]. Occurring in up to 1% of the general population - typically young men and women aged 25 or older - AS is a painful, debilitating condition primarily associated with swelling, in severe cases fusion of the spine (bones growing together), and irreversible bone formation (new bones growing)[6],[7]. It can cause persistent back pain, stiffness, fatigue and curvature of the spine that result in patients becoming progressively disabled and unable to work[1],[2]. People with AS have very few therapeutic options available to them. In case of non-response to non-steroidal anti-inflammatory drugs (NSAIDs), anti-TNF medicines are the only currently available biologic treatment alternative but are not effective for all patients, representing a substantial unmet need[1].
Joint regulatory applications for secukinumab in AS and PsA are planned for 2015. This follows the secukinumab global regulatory applications for moderate-to-severe plaque psoriasis which were filed in October 2013 with regulatory decisions anticipated in late 2014 or early 2015.
MEASURE 1 and MEASURE 2 are randomized, placebo-controlled, multicenter studies designed to demonstrate efficacy of secukinumab in AS compared to placebo and to assess safety, tolerability and long-term effectiveness. The Assessment of Spondyloarthritis International Society criterion (ASAS 20) was the primary endpoint. Secukinumab showed an acceptable safety profile in both studies which was consistent with that observed in the large psoriasis clinical trial program, involving approximately 4,000 patients[8].
about ankylosing spondylitis (AS)$ ? ]2 c- f2 R9 n" O# M
Ankylosing spondylitis (AS) is a common type of spondyloarthropathy (SpA), a family of long-term diseases of joints (inflammatory disease)[5]. Up to 70% of patients with severe AS can develop spinal fusion (bones grow together), significantly reducing mobility and quality of life[2],[9],[10]. AS occurs in up to 1% of the general population and typically affects young men and women aged 25 or older[6],[7]. Certain genetic factors increase a person's risk of developing AS by more than 50%[11].
about secukinumab (AIN457) and interleukin-17A (IL-17A). p, i& ]7 _* ^& K2 p+ M
Secukinumab (AIN457) is a fully human monoclonal antibody that selectively neutralizes the action of IL-17A[3]. Secukinumab is the first medicine selectively targeting IL-17A with positive Phase III results for the treatment of AS. IL-17A, a protein that stimulates inflammation, is central to the development of psoriasis and other inflammatory arthritic diseases, including AS[4].
In addition to AS, secukinumab is also in clinical trials for the treatment of psoriasis arthritis (PsA) and rheumatoid arthritis (RA). Global regulatory applications for secukinumab in AS and PsA are planned for 2015. This follows the secukinumab global regulatory applications for moderate-to-severe plaque psoriasis which were filed in October 2013 with approvals anticipated in late 2014 or early 2015.
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