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新重组单抗Cosentyx(secukinumab)获美国FDA批准上市

2015-01-22 21:38:31 作者：新特药房来源：互联网浏览次数：731 文字大小：【大】【中】【小】

简介： 2015年1月21日，美国食品和药品监管局(FDA)批准Cosentyx (secukinumab)治疗有中度至严重斑块性银屑病成年。银屑病是一种皮肤情况致皮肤发红和刺激斑点块。银屑病是一种自身免疫疾病，和在有疾病家族史患者 ...

关键字：依那西普 secukinumab 药品商标名cosentyx 新重组单抗斑块性银屑病

2015年1月21日，美国食品和药品监管局(FDA)批准Cosentyx (secukinumab)治疗有中度至严重斑块性银屑病成年。
银屑病是一种皮肤情况致皮肤发红和刺激斑点块。银屑病是一种自身免疫疾病，和在有疾病家族史患者中更常发生，和在年龄15和35人们间大多数往往良性。银屑病的最常见形式是斑块性银屑病，其中患者发生厚，有小薄片红皮肤，银白色的斑块被称为鳞。
Cosentyx的活性成分是依那西普[secukinumab]。依那西普是一种抗体结合至一种涉及炎症中的蛋白(白介素(IL)-17A)。通过结合至IL-17A，依那西普阻止它结合至其受体，和抑制其触发在斑块性银屑病发展中起作用的炎症反应。
Cosentyx是在皮下注射给予。它意向为被选患者全身治疗(在通过口或注射后利用物质经血流旅行治疗)，光治疗(紫外线治疗)或两者的联合。
FDA的药品评价和研究中心药物评价III室副主任Amy Egan, M.D., M.P.H.,说：“斑块性银屑病可能致患者显著皮肤刺激和不适，所以重要的是患者可得到各种各样治疗选择。”
在四项临床试验总共2,403例有斑块性银屑病参加者是为光治疗或全身治疗的被选者中确定Cosentyx的安全性和有效性。参加者被随机赋予至接受Cosentyx或一种安慰剂。结构显示 Cosentyx比安慰剂实现更大的临床反应，通过评分皮肤银屑病变化的程度，性质和严重程度评估皮肤清除或几乎清除。
Cosentyx正在被批准有一个用药指南告知患者，因为Cosentyx是一种药物影响免疫系统，患者可能有更大风险获得感染。曾报道使用Cosentyx 严重过敏反应。在有某种慢性感染或复发性感染病史患者，和在有活动性克罗恩病[Crohn’s Disease]患者中当考虑使用Cosentyx时应谨慎行事。最常见副作用包括腹泻和上呼吸道感染。
Cosentyx由总部新泽西东汉诺威Novartis Pharmaceuticals Corporation上市。
剂型优势
冻干粉
剂型：
预充式注射器
规格：150mg/瓶
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: 300mg 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
Safety and efficacy not established
New Drugs Online Report for secukinumab
Information
Generic Name: secukinumab
Trade Name: Cosentyx
Synonym: AIN 457, AIN457
Entry Type: New molecular entity
Developmental Status
UK: Approved (Licensed)
EU: Approved (Licensed)
US: Recommended for approval (Positive opinion)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
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:
Method(s) of Administration
Subcutaneous
Company Information
Name: Novartis
US Name: Novartis
NICE 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