重组单抗Cosentyx(TM)被欧盟批准用于中、重度银屑病一线治疗 --Cosentyx 是可用于银屑病的一线全身治疗的唯一生物制剂，并且可代替其他具有显著副作用的治疗；所有其他生物制剂被推荐作为二线治。 --IIIb期 CLEAR 研究显示Cosentyx 优于优特克单抗(ustekinumab) --III期研究显示，70%接受 Cosentyx 300mg 治疗的患者在治疗最初16周内皮损完全消除(PASI 100) 或接近完全消除 (PASI 90) --对银屑病患者而言，皮损消除是最终的治疗目标；50%的银屑病患者对现有治疗不满意 2015年1月26日,欧盟委员会(EC) 批准Cosentyx（secukinumab，曾用名AIN457），用于适合接受全身治疗的中、重度斑块型银屑病成年患者的一线全身治疗。 Cosentyx(剂量300mg)是首个也是唯一获得欧盟批准的白细胞介素-17A(IL-17A)抑制剂。这一批准标志着银屑病治疗的重要里程碑，为患者提供了一种新的重要一线生物制剂治疗选择。目前在欧洲，包括抗肿瘤坏死因子（抗TNF）药物和优特克单抗 (ustekinumab)在内的所有治疗银屑病的生物制剂均被推荐作为二线全身治疗。 诺华制药全球负责人David Epstein 表示，“欧盟传来的好消息意味着银屑病患者将可能实现完全消除皮损的梦想。近半数的银屑病患者对包括生物制剂治疗在内的现有治疗并不满意，这说明患者的治疗需求还远未得到满足。作为银屑病一线全身治疗药物，Cosentyx将可提高患者皮损完全消除或接近完全消除的可能性。” 银屑病治疗的关键目标是皮损完全消除，皮肤恢复正常。临床研究显示， 70%接受Cosentyx 300mg治疗的患者在治疗最初16周内皮损完全消除(PASI 100)或接近完全消除(PASI 90)，并且重要的是，大部分患者在继续接受治疗的情况下，皮损完全消除或接近完全消除的效果可维持至第52周。来自Cosentyx临床试验的数据也显示，皮损完全消除或接近完全消除与银屑病患者的健康相关生活质量之间存在显著正相关。 欧盟的批准决定主要基于IIIb期CLEAR研究的最新结果，该研究显示Cosenty在消除中、重度斑块型银屑病患者的皮肤方面优于优特克单抗。CLEAR研究是Cosentyx的第2项头对头研究。FIXTURE研究也显示，Cosentyx 在消除皮损方面优于依那西普。III期临床试验显示，Cosentyx的总体安全性较好，并且在头对头研究中与依那西普和优特克单抗之间的差异非常小。 除了欧盟之外，Cosentyx 还被澳大利亚批准用于治疗中、重度斑块型银屑病和被日本批准用于治疗中、重度斑块型银屑病和活动性银屑病关节炎 (PsA)。 2014年10月皮肤科和眼科药物咨询委员会 (DODAC) 全体成员一致建议美国食品药品管理局(FDA)批准Cosentyx用于治疗中、重度斑块型银屑病。 Cosentyx尚未在中国获得批准。 关于Cosentyx(secukinumab)和白细胞介素-17A（IL-17A） Cosentyx是选择性白细胞介素-17A(IL-17A)的人类单克隆抗体。IL-17A在银屑病受累皮肤中的浓度较高，是试验性治疗的首选靶点。Cosentyx通过抑制IL-17A的作用来发挥疗效。III期项目显示，Cosentyx的安全性较好，secukinumab 300mg治疗组和150mg治疗组的不良事件严重度和发生率相似。 有关使用 Cosentyx治疗掌跖银屑病、指甲银屑病和掌跖脓疱病的IIIb期银屑病研究正在进行中。 有关使用 Cosentyx治疗银屑病关节炎(PsA)和强直性脊柱炎(AS)的III期研究也正在进行中；计划在2015年向监管部门递交申请材料。 关于银屑病 银屑病是一种慢性免疫介导性疾病，其特征为厚且广泛的皮肤病变（称为斑块），伴有瘙痒、脱屑和疼痛；该病与生理和心理生活质量明显下降相关。银屑病大约累及全球3%的人口，全球患者总人数超过1.25亿。在欧洲，患病率估计为0.8%，意味着约370万欧洲人患有斑块型银屑病，约240万被认为患有中至重度疾病。 这一常见且令人困扰的疾病不仅仅是影响美观的问题-甚至症状非常轻微的患者也每天处于困扰中。此外，由于高达50%的银屑病患者对包括生物制剂治疗在内的现有治疗并不满意，因此目前亟需治疗银屑病的新型药物。 New Drugs Online Report for secukinumab Information Generic Name: secukinumab   Trade Name: Cosentyx  Synonym: AIN 457, AIN457  Entry Type: New molecular entity   Development and Regulatory status UK: Approved (Licensed)  EU: Approved (Licensed)  US: Approved (Licensed)  UK launch Plans: Available only to registered users Actual UK launch date:   Comments Jan 15: US FDA has approved secukinumab (Cosentyx) for the treatment of moderate-to-severe plaque psoriasis in adults who are eligible for systemic therapy or phototherapy [26].  23/01/2015 09:30:29  Jan 15: Approved in the EU [25]. 20/01/2015 13:38:21  Nov 14: EU positive opinion for secukinumab as a first-line treatment of moderate-to-severe plaque psoriasis [23]. 21/11/2014 11:25:14  Oct 14: Secukinumab recommended for approval by US FDA panel. Formal approval expected later this year.[22]  20/10/2014 17:47:12  Oct 14: Secukinumab will be reviewed by a US FDA advisory committee meeting on October 20. EU decision expected 2015 [21]. 13/10/2014 11:19:54  Dec 13: Filed in the EU [17] 19/12/2013 11:40:55  Oct 13: Company still plans to file in the EU and US by end of 2013 [15]. 04/10/2013 09:44:15  Nov 12: regulatory filings expected to start in late 2013 [11].  09/11/2012 14:55:37  Apr 12: Filings now planned for 2014 [8]. 12/06/2012 14:15:26  Aug 11: Filings planned for 2013 [3]. 16/08/2011 10:50:53  Jun 11: PIII studies start [1] 24/06/2011 11:35:49  Trial or other data Dec 14: Secukinumab met the primary endpoint of achieving PASI 90, which represents clear or almost clear skin at Week 16, and had a beneficial secondary endpoint of achieving PASI 75 at Week 4 for psoriasis patients in the CLEAR study (n=679). The trial is the second head-to-head trial conducted pitting secukinumab against ustekinumab and will be submitted for presentation at an international medical congress in 2015. [24] 15/12/2014 09:57:41 Oct 14: New analyses of PIII studies presented at the European Association of Dermatology and Venereology congress in Amsterdam which show that treatment with secukinumab 300mg resulted in higher rates of clear to almost clear skin at week 12 versus placebo, regardless of patients´ psoriasis disease severity. The majority of patients across two disease severity subgroups, including those with severe psoriasis, experienced complete clear to almost clear skin (100% or 90% reduction by the PASI index). Skin clearance was sustained through one year of treatment [21]. 13/10/2014 11:17:55 July 14: New England Journal of Medicine published the results from two pivotal Phase III studies evaluating the interleukin-17A (IL-17A) inhibitor secukinumab (AIN457). Secukinumab met all primary and key secondary endpoints in the ERASURE and FIXTURE studies, including Psoriasis Area and Severity Index (PASI) 75 and 90 and Investigator´s Global Assessment modified 2011 (IGA mod 2011) 0/1 responses. [20] 11/07/2014 08:30:35 Mar 14: Results reported from the pivotal PIII FEATURE and JUNCTURE studies at the AAD meeting. These studies evaluated secukinumab administered with a pre-filled syringe (PFS) or autoinjector/pen (AI), which allow self-administration. In both studies more secukinumab 300mg patients achieved almost clear skin (PASI 90) at Week 12 (60.3% for FEATURE and 55% for JUNCTURE, p<0.0001) vs placebo. The studies met all primary and pre-specified secondary endpoints. Across the co-primary endpoints, secukinumab 300mg demonstrated significant improvements in PASI 75 at Week 12 vs placebo (75.9% vs. 0% for FEATURE; 86.7% vs. 3.3% for JUNCTURE, p<0.0001), and was also superior to placebo according to the Investigator´s Global Assessment (IGA mod 2011). By Week 3, patients on secukinumab 300mg experienced superior efficacy in clearing skin vs placebo[1],[2]. In addition, the 300mg dose showed numerically and clinically relevant improvements vs 150 mg. At Week 1, all patients successfully self-injected following instructions; patient satisfaction scores were consistently high, showing acceptability of the PFS and AI [19] 25/03/2014 08:27:49 Mar 14: NCT02074982 is a randomised double-blind study comparing secukinumab, to ustekinumab, in 640 patients with plaque-type psoriasis. The primary outcome is PASI at 16 weeks. The study starts Feb 14 and is due to complete Oct 15 [18]. 06/03/2014 14:18:14 Dec 13: NCT02008890 a 52-week, multicentre, randomized, double-blind, placebo-controlled study of subcutaneous secukinumab to demonstrate efficacy as assessed by palmoplantar pustulosis Psoriasis Area and Severity Index (ppPASI 75) at 16 weeks of treatment, compared to placebo, and to assess long-term safety, tolerability, and efficacy for up to 52 weeks in 210 subjects with moderate to severe chronic palmoplantar pustular psoriasis. The study starts Dec 13 and is due to complete Mar 16 [17]. 13/12/2013 11:20:13 Oct 13: NCT01961609 (SIGNATRURE) is a PIII open-label, non-comparator, UK study of secukinumab in 288 patients with moderate to severe active, chronic plaque psoriasis who have failed on TNF α antagonists. The primary outcome is PASI 75 response rate after 12 weeks treatment. The study starts Oct 13 and is due to complete Nov 15 [16]. 14/10/2013 11:03:21 Oct 13: Results from the head-to-head PIII FIXTURE study reported at EADV. The study met all primary and pre-specified key secondary endpoints (p<0.0001 for placebo comparisons and p=0.025 for etanercept comparisons). Both doses of secukinumab showed improved efficacy to etanercept over 52 weeks, beginning as early as Week 2 and confirmed by Week 12 when the primary endpoints were assessed (PASI 75 and the Investigator´s Global Assessment mod 2011). More secukinumab patients experienced almost clear skin (PASI 90) and completely clear skin (PASI 100) vs etanercept. 72% of secukinumab 300mg patients experienced PASI 90 by Week 16 (54% as early as Week 12 vs 21% of etanercept patients). 24% vs 4%, respectively achieved PASI 100 at Week 12. Secukinumab efficacy was sustained over 1 year; 65 % of patients on secukinumab 300mg vs 33% on etanercept had a PASI 90 score at week 52. The incidence of AEs was similar between both secukinumab treatment arms (300 mg and 150 mg), and was comparable to etanercept. The most common AEs in any treatment group were nasopharyngitis and headache. Serious AEs were experienced by 6% of secukinumab 300mg, 5% of secukinumab 150mg and 6% of etanercept patients. No deaths were reported [15]. 04/10/2013 09:42:11 Jul 13: NCT01900782 (FIXTURE 2) is a randomized, double-blind, multicentre PIII study to demonstrate efficacy of treatment of secukinumab (150 or 300mg) vs placebo and etanercept, and to assess the safety, tolerability and long-term efficacy up to 1 year in 920 subjects with moderate to severe chronic plaque-type psoriasis. The co-primary endpoints are the number of patients with PASI 75 response and with IGA mod 2011 0 or 1 response at week 12. The study starts Oct 13 and is due to complete Jun 15 [14]. 18/07/2013 15:04:06 Jul 13: Top-line results from the PIII FIXTURE trial reported to show that sc secukinumab was superior to etanercept, and that it met all primary and secondary study endpoints [13]. 08/07/2013 21:01:44 Jul 12: NCT01640951 (CAIN457A2304E1) is a PIII extension study to two ongoing PIII studies, CAIN457A2304 and CAIN457A2307 and is planned to collect up to 2 years safety data on secukinumab in both the fixed interval regimen and the retreatment at start of relapse regimen. All subjects (n=740) completing Week 52 of CAIN457A2304 and Week 40 of CAIN457A2307 will be eligible to participate. Prefilled syringe liquid formulation of secukinumab will be used. The study will start Sep 12 and is due to complete May 15 [10]. 20/07/2012 10:33:42 Jul 12: NCT01636687 (JUNCTURE) is a PIII randomized, double-blind, placebo controlled, multicenter study of subcutaneous secukinumab in autoinjectors (150 and 300mg) to demonstrate efficacy after 12 weeks and to assess the safety, tolerability, usability and long-term efficacy in 171 subjects with chronic plaque-type psoriasis. The primary outcome is PASI75 score and Investigators´ Global Assessment (IGA) with 0 or 1 response at 12 weeks. The study will start Sep 12 [9]. 12/07/2012 10:30:01 Mar 12: NCT01555125 (FEATURE) A PIII, double-blind, placebo controlled, multicentre RCT of subcutaneous secukinumab (150 or 300mg) in prefilled syringes to demonstrate efficacy after 12 weeks of treatment in 171 subjects with chronic plaque-type psoriasis. The primary outcome is PASI 75 score and Investigators´ Global Assessment (IGA) with 0 or 1 response. The study will start May 12 and is due to complete Mar 14 [6]. 16/03/2012 13:45:58 Mar 12: NCT01544595 A PIII extension study of secukinumab prefilled syringes in 1,220 subjects with moderate to severe chronic plaque-type psoriasis completing preceding 52-week psoriasis PIII studies with secukinumab. The study is planned to collect an additional 2 years of long-term efficacy, safety, and tolerability data of secukinumab in either continuous or interrupted therapy (randomized withdrawal period) in subjects showing at least partial response to secukinumab and completing treatment period on secukinumab in previous PIII studies. The primary outcome is cumulative rate of subjects with loss of PASI 75 response up to week 68. The study will start Jun 12 and is due to complete May 15 [5]. 12/03/2012 10:33:40 Oct 11: Positive results from three Phase II trials showing that secukinumab produced a quick and significant improvement of symptoms in patients with moderate-to-severe plaque psoriasis. Results were presented at the annual European Academy of Dermatology and Venereology (EADV) Congress, Lisbon, Portugal. In one study, 81% of patients receiving secukinumab 150mg sc once a month experienced at least a 75% improvement of psoriasis signs and symptoms as measured by PASI (Psoriasis Area and Severity Index) vs 9% for placebo at week 12 (p<0.001). In another study, results also showed that 83% of patients who were given an IV starting dose of secukinumab experienced at least a 75% improvement of symptoms vs 10% for placebo. A third study showed that receiving secukinumab in the first month was beneficial to 55% of patients vs 2% for placebo at week 12 (p<0.001). [4]  25/10/2011 08:17:42 Aug 11: NCT01412944 (STATURE) is a PIII RCT Study to assess the safety and long-term efficacy of IV (10mg/kg) and sc (300mg) secukinumab in 140 subjects with moderate to severe chronic plaque-type psoriasis who are partial responders to secukinumab (have participated in study CAIN457A2304 and have achieved a partial response - PASI 50 not 75 - after 12 weeks). The primary outcome is PASI 75 reponse and IGA 0 or 1 response at week 8. The study will start Nov 11 and is due to complete Jul 13 [2]. 12/08/2011 10:05:37 NCT01358578 (FIXTURE) and NCT01365455 (ERASURE): are PIII multicentre studies to demonstrate efficacy of secukinumab vs placebo after 12 weeks, and to assess the safety, tolerability and long-term efficacy up to 1 year in 1264 and 720 subjects with moderate to severe chronic plaque-type psoriasis, respectively. The primary outcome is PASI (psoriasis area and severity index) and IGA (investigator´s global assessment) vs placebo. ERASURE will employ doses of 150 and 300mg secukinumab, and FIXTURE 50, 150 and 300mg. FIXTURE also has an active control arm comprising etanercept. The studies start in Jun 11 and are due to complete Mar 13 [1]. 24/06/2011 11:29:22 Evidence Based Evaluations NICE scope  http://www.nice.org.uk/Guidance/InDevelopment/GID-TAG460/Documents  NHSC  http://www.nhsc-healthhorizons.org.uk/files/downloads/1805/2208.7d53ef75.Secukinumab.pdf  References   Available only to registered users  Category BNF Category: Drugs affecting the immune response (13.05.03) Pharmacology: fully human IgG1k anti-IL17A antibody   Epidemiology: Prevalence is thought to vary among ethnic groups, with a higher prevalence among Scandinavian populations. Approximately 2% of Europeans have psoriasis: plaque psoriasis is the most common type, representing 90% of cases. [7]   Indication: Psoriasis  Additional Details: moderate-to-severe plaque in adults - first-line  Method(s) of Administration   Subcutaneous  Company Information Name: Novartis  US Name: Novartis  Further Information Anticipated Commissioning route (England) NHSE  In timetable: Yes   When: Jul / 2015  Note: www.nice.org.uk/Guidance/InDevelopment/GID-TAG460   PbR Yes - Likely PBR    Implications Available only to registered users Comments