Cosentyx (secukinumab) solution for injection 中度至重度牛皮癣(银屑病)患者 IL-17阻断剂
Dosage Forms & Strengths
lyophilized powder for reconstitution
150mg/vial
solution for injection
150mg/prefilled syringe
150mg/Sensoready pen
Psoriasis
Indicated for moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy
Initial: 300 mg SC at weeks 0, 1, 2, 3, and 4
Monthly maintenance: Beginning at week 8, give 300 mg SC once monthly
For some patients, a dose of 150 mg may be acceptable
Cosentyx (secukinumab) ha recibido opinión positiva del CHMP para psoriasis en placas moderada/grave
Cosentyx™ (secukinumab, antes conocido como AIN457) está recomendado como tratamiento sistémico de primera línea para la psoriasis en placas moderada / grave en pacientes adultos en Europa.
En estudios de Fase III, el 70% o más de los pacientes consiguió un blanqueamiento total (PASI 100) o casi total (PASI 90) con secukinumab 300 mg durante las 16 primeras semanas de tratamiento.
Los ensayos clínicos mostraron de forma consistente un blanqueamiento muy elevado de la piel, una eficacia sostenible y un perfil de seguridad favorable para secukinumab.
Novartis ha anunciado hoy que el Comité de Medicamentos de Uso Humano (CHMP, por sus siglas en inglés) se ha pronunciado a favor de la aprobación de Cosentyx™ (secukinumab, antes conocido como AIN457) como tratamiento sistémico de primera línea para tratar la psoriasis en placas de moderada a grave en adultos que son candidatos a un tratamiento sistémico.
Una recomendación de primera línea significaría que los médicos podrían utilizar secukinumab para tratar la psoriasis de los pacientes antes de emplear medicamentos como la ciclosporina y el metotrexato, que tienen efectos secundarios significativos. Actualmente, todos los tratamientos biológicos para la psoriasis, incluyendo los tratamientos con factor de necrosis anti-tumoral (anti-TNF) y ustekinumab, se recomiendan como tratamiento sistémico de segunda línea en Europa.
Secukinumab (a una dosis de 300 mg) es el primer inhibidor de la interleuquina-17A (IL-17A) que tiene una recomendación con opción a tratamiento de primera línea para los pacientes con psoriasis que precisan tratamiento sistémico en Europa. Secukinumab trabaja inhibiendo la acción de la IL-17A, una proteína que se encuentra en altas concentraciones en la piel afectada por la enfermedad.
“La opinión favorable del CHMP para secukinumab como tratamiento de primera línea de la psoriasis nos acerca un poco más a su aprobación en Europa y a hacer del blanqueamiento dérmico una realidad para los pacientes con psoriasis”, señala David Epstein, Director de División de Novartis Pharmaceuticals. “Con estas emocionantes noticias, podemos cambiar la manera de tratar la psoriasis, ya que el 50% de los pacientes está insatisfecho con su tratamiento, lo que muestra una necesidad urgente de nuevos tratamientos que blanqueen la piel más rápido y durante más tiempo ”.
El objetivo final del tratamiento de la psoriasis es blanquear la piel de los pacientes. En estudios clínicos, el 70% o más de los pacientes lograron blanqueamiento total (PASI 100) o casi total (PASI 90) con secukinumab 300 mg en las 16 primeras semanas de tratamiento.
La opinión del CHMP se ha basado en los resultados positivos del programa de ensayos clínicos de Fase III de psoriasis en placas de moderada a grave y se suma a la recomendación unánime para su aprobación emitida en octubre por el Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) de la Food and Drug Administration (FDA) de Estados Unidos.
En estos ensayos, secukinumab demostró de forma consistente un elevado blanqueamiento de la piel, superior a Enbrel®** (etanercept) en el estudio comparativo FIXTURE. El 70% o más de los pacientes que recibieron secukinumab 300 mg lograron un blanqueamiento total (PASI 100) o casi total (PASI 90) durante las primeras 16 semanas de tratamiento en los estudios FIXTURE y ERASURE, lo que se mantuvo en la mayoría de los pacientes hasta la semana 52 (con tratamiento continuado).
Los pacientes tratados con secukinumab en los estudios FIXTURE, ERASURE, FEATURE y JUNCTURE (revisados por la FDA) también observaron diferencias significativas desde la semana 2 y, de media, los pacientes de secukinumab 300 mg experimentaron una reducción de sus síntomas del 50% en la semana 3, comparado con la semana 7 para los pacientes de Enbrel®** (etanercept) en FIXTURE. Secukinumab demostró un perfil de seguridad favorable, con una incidencia y gravedad de los acontecimientos adversos similar entre los grupos de tratamiento de secukinumab (300 mg y 150 mg).
La Comisión Europea revisa las recomendaciones del CHMP. La decisión final sobre la aprobación, que suele concederse a los dos meses de la opinión del CHMP, será aplicable a los países de la Unión Europea (UE) y del Espacio Económico Europeo .
Name(s) COSENTYX
FDA Application No. (BLA) 125504
Active Ingredient(s) SECUKINUMAB
Company NOVARTIS PHARMS CORP
Original Approval or Tentative Approval Date January 21, 2015
Chemical Type 1 New molecular entity (NME)
View the label approved on 01/21/2015 (PDF) for COSENTYX, BLA no. 125504
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 eva luating 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 eva luated 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 eva luations
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: Preva lence is thought to vary among ethnic groups, with a higher preva lence 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) -
In timetable: Yes
When: Jul / 2015
Note: www.nice.org.uk/Guidance/InDevelopment/GID-TAG460
PbR Awaiting Update
PBR Likely specified high cost drug.
Implications Available only to registered users
Cosentyx (secukinumab)获批主要是因为III期临床研究表明，该药在消除皮肤中重度斑块状银屑病以及改善银屑病关节炎的症状和体征方面具有显著且持久的疗效。
许多患者对现有银屑病或银屑病关节炎治疗无应答或不耐受，提示这类疾病的治疗需求尚未充分满足。
银屑病关节炎累及全球大约30%的银屑病患者，可能导致不可逆转的关节损害；如今该药获准上市，患者便有了新的治疗选择，可以同时有效治疗这两种疾病。III期研究显示，在接受了Cosentyx 300 mg治疗的患者中≥70%在开始治疗后16周内实现了皮损完全消除(PASI 100)或皮损接近完全消除 (PASI 90) 。
诺华公司日前宣布，日本厚生劳动省(MHLW)正式批准Cosentyx (secukinumab，曾用名AIN457)用于对全身性治疗(除外生物制剂)应答不足的寻常型银屑病和银屑病关节炎(PsA)成年患者。这使得日本成为了全球第一个批准Cosentyx的国家，也使得Cosentyx成为了首个在日本获准用于上述两种适应症的白介素-17A (IL-17A)抑制剂。
Cosentyx主要通过抑制 IL-17A 发挥作用，IL-17A 蛋白在银屑病受累皮肤中浓度较高，是银屑病、PsA等炎性疾病发病的关键因素。全球大约30%的银屑病患者同时也患有PsA；如今该药获批意味着日本患者有了新的治疗选择，可以同时有效治疗这两种疾病。
诺华制药全球负责人David Epstein表示：“我们很高兴日本在全球率先批准Cosentyx用于治疗银屑病和银屑病关节炎，为日本超过400,000名银屑病和银屑病关节炎患者提供新的治疗选择。”“将近一半的银屑病和PsA患者对现有治疗不满意。如今该药获准上市，我们应该能够解决这一重要的尚未满足的治疗需求，切实提高这些患者的生活质量。”
在银屑病临床试验中，70%的患者在开始Cosentyx 300 mg治疗后16周内实现了皮损完全消除或皮损接近完全消除 (p<0.0001)，并且在大部分患者中这一效果一直持续至第52周(继续接受治疗)1。在PsA试验中，Cosentyx与安慰剂相比在改善PsA的症状和体征方面疗效显著且持久，具体表现为美国风湿病学会应答标准评分下降20%(ACR 20)，这是评估关节炎治疗疗效的公认标准。在两项关键性试验FUTURE 1 (150 mg；p<0.0001)和FUTURE 2 (150和300 mg；p<0.0001)中，50%~54%接受了Cosentyx治疗的患者至少达到了ACR 20 。
银屑病是一种慢性免疫介导性疾病，其特征是皮损厚而广泛，称为斑块，已知会引起瘙痒、脱屑和疼痛；银屑病可能明显影响患者生理和心理方面的生活质量。PsA与银屑病密切相关，可能引起关节疼痛和僵硬、皮肤和指甲银屑病、手指脚趾肿胀、持续性疼痛性肌腱炎以及不可逆转的关节损害。多达40%的患者可能发生关节破坏和永久性身体畸形。
Cosentyx获批主要是基于相关研究的安全性和疗效结果，包括10多项总共纳入了将近4,000例中重度斑块状银屑病患者的II期和III期试验 以及2项纳入了1,000多例 PsA患者的关键性III期试验 FUTURE 1和FUTURE 。在所有试验中，Cosentyx均表现出了良好的安全性特征，两个Cosentyx 治疗组(300 mg和150 mg)的不良事件 (AEs)发生率和严重程度相似 。
2014年11月，Cosentyx 获得了欧洲药品管理局人用药品委员会(CHMP)的积极意见，推荐欧洲各国将Cosentyx作为中重度银屑病患者的一线治疗。并于2014年10月获得了FDA皮肤与眼科药物顾问委员会(DODAC)对该适应症的全票支持。
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。据估计，日本大约有430,000名银屑病患者。
这种令人痛苦的常见病并非单纯的美观问题，即使患者症状很轻，其日常生活也会受到影响。而且，多达50%的患者对包括生物制剂在内的现有治疗并不满意，因此急需新的银屑病治疗药物。
Cosentyx是一种选择性中和IL-17A的人单克隆抗体。IL-17A在银屑病受累皮肤中浓度较高，是试验性治疗药物的首选靶点。研究还表明，在银屑病关节炎、强直性脊柱炎等其他炎性关节疾病中，IL-17A在促进机体免疫应答方面也起着重要的作用。
针对银屑病关节炎和强直性脊柱炎的III期研发计划正在进行中；预计2015年世界各国将陆续批准Cosentyx用于治疗这些关节疾病。
银屑病关节炎(PsA)是一种使人日渐衰弱的长期炎性疾病，可能引起明显残疾、生活质量下降以及寿命缩短。PsA累及大约0.3%~1%的总人口，多达四分之一的银屑病患者可能都合并有PsA，只是有的未被诊断。在日本，PsA累及超过3%的银屑病患者
