Secukinumab
(Synonyms: 司库奇尤单抗; AIN457) 目录号 : GC19532
苏金单抗作为一种抗白细胞介素17A的单克隆抗体，通常用于治疗强直性脊柱炎。
Cas No.:875356-43-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
CMSC cells(Human chorionic derived mesenchymal stem cells) |
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Preparation Method |
Secukinumab was collected and purified from transduced CMSC cells. Cultured human dermal fibroblasts were incubated with IL-17A (15 ng/ml) in the presence of increasing concentrations of the secukinumab antibody(2-3 µg). After 48 hours the production of IL-6 in these cells was quantified using an ELISA kit (Abcam, UK) as an indicator of secukinumab functionality. |
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Reaction Conditions |
2-3 µg; 48h |
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Applications |
After 72 hours reduced IL-6 secretions from fibroblasts confirmed the inhibitory activity of secukinumab on human IL-17. |
| Animal experiment [2]: | |
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Animal models |
Balb/c female mice |
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Preparation Method |
The mice in the control group received 100 μL phosphate-buffered saline (PBS), while the mice in other groups received 100 μL (100 μg) BLM in PBS subcutaneously (sc) every day for 4 weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10 mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50 mg/kg/d for 28 days. |
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Dosage form |
10 mg/kg/wk sc |
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Applications |
Secukinumab and metformin ameliorated dermal fibrosis. |
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References: [1]. Fallah A, et al. Biosimilar Gene Therapy: Investigational Assessment of Secukinumab Gene Therapy. Cell J. 2020 Jan;21(4):433-443. [2]. Karatas A, et al. Secukinumab and metformin ameliorate dermal fibrosis by decreasing tissue interleukin-17 levels in bleomycin-induced dermal fibrosis. Int J Rheum Dis. 2021 Jun;24(6):795-802. |
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Secukinumab, as an anti-interleukin-17A monoclonal antibody, usually used for treatment with the ankylosing spondylitis[1].
In vitro experiment it indicated that when IL-17A at 956.2 ng/mL, secukinumab was obviously less potent[2].
In vivo clinical trail it suggested that treatment with 150 mg secukinumab subcutaneously or intravenously in patients remarkedly reduced the signs and symptoms of ankylosing spondylitis at week 16. While treatment with 75 mg secukinumab subcutaneously caused obvious improvement only with a higher intravenous loading dose.[1] Secukinumab has a highly favorable safety profile. In clinical test it demonstrated that treatment with 300 mg secukinumab, for occurs at a rate of 3.55/100 subject-years of mucocutaneous candidiasis, these infections usually do not interfere with maintenance of secukinumab therapy. Thus, secukinumab has an effictive new treatment for individuals with moderate-to-severe psoriasis.[3] In pivotal phase III trials, at dose of 75–150 mg and 75–300 mg secukinumab subcutaneously in pediatric patients aged 6 to < 18 years, there is an markedly improvemnet compared with placebo. It is suggested that secukinumab improved health-related quality of life and was generally well tolerated. [4] In efficacy trail it indicated that in received subcutaneous secukinumab 150?mg with (LD) or without (NL) loading dose patients or placebo weekly, secukinumab significantly improved the signs and symptoms of nr-axSpA across patients grouped by C-reactive protein (+/?) and/or magnetic resonance imaging (+/?) status, HLA-B27 (+/?) status, and sex[5].
References:
[1]Baeten D, et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015 Dec 24;373(26):2534-48.
[2]Adams R, et al. Bimekizumab, a Novel Humanized IgG1 Antibody That Neutralizes Both IL-17A and IL-17F. Front Immunol. 2020 Aug 21;11:1894.
[3]Blauvelt A. Safety of secukinumab in the treatment of psoriasis. Expert Opin Drug Saf. 2016 Oct;15(10):1413-20.
[4]Blair HA. Secukinumab: A Review in Moderate to Severe Pediatric Plaque Psoriasis. Paediatr Drugs. 2021 Nov;23(6):601-608.
[5]Braun J, et al. Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT. Arthritis Res Ther. 2021 Sep 4;23(1):231.
苏金单抗作为一种抗白细胞介素17A的单克隆抗体,通常用于治疗强直性脊柱炎[1]。
体外实验表明,当IL-17A浓度为956.2 ng/mL时,苏金单抗的作用明显减弱[2]。
体内临床试验表明,在第 16 周时,皮下或静脉注射 150 mg 苏金单抗可显着减轻强直性脊柱炎的症状和体征。而皮下注射 75 mg 苏金单抗仅在较高的静脉负荷剂量下才会有明显改善.[1] 苏金单抗具有高度有利的安全性。在临床试验中,它证明用 300 mg 苏金单抗治疗,以 3.55/100 受试者年的比率发生皮肤粘膜念珠菌病,这些感染通常不会干扰苏金单抗治疗的维持。因此,苏金单抗对于中度至重度银屑病患者来说是一种有效的新疗法。[3]在关键的 III 期试验中,苏金单抗皮下注射 75-150 mg 和 75-300 mg 苏金单抗用于儿科6 岁至 < 的患者； 18年,与安慰剂相比有明显改善。这表明苏金单抗改善了与健康相关的生活质量,并且总体上耐受性良好。 [4] 在疗效试验中,它表明在每周接受皮下注射苏金单抗 150mg 负荷剂量 (LD) 或不负荷剂量 (NL) 或安慰剂的患者中,苏金单抗显着改善了 nr-axSpA 的体征和症状按 C 反应蛋白 (+/-) 和/或磁共振成像 (+/-) 状态、HLA-B27 (+/-) 状态和性别分组的患者[5]。
| Cas No. | 875356-43-7 | SDF | |
| 别名 | 司库奇尤单抗; AIN457 | ||
| 分子式 | C6584H10134N1754O2042S44 | 分子量 | 147941.89 |
| 溶解度 | 储存条件 | Store at 4°C, Do not freeze | |
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.0068 mL | 0.0338 mL | 0.0676 mL |
| 5 mM | 0.0014 mL | 0.0068 mL | 0.0135 mL |
| 10 mM | 0.0007 mL | 0.0034 mL | 0.0068 mL |
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Bimekizumab versus Secukinumab in Plaque Psoriasis
N Engl J Med2021 Jul 8;385(2):142-152.PMID: 33891380DOI: 10.1056/NEJMoa2102383
Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
Methods: In this phase 3b trial, we randomly assigned patients with moderate-to-severe plaque psoriasis, in a 1:1 ratio, to receive bimekizumab subcutaneously at a dose of 320 mg every 4 weeks or secukinumab subcutaneously at a dose of 300 mg weekly to week 4, followed by every 4 weeks to week 48. At week 16, patients receiving bimekizumab underwent rerandomization, in a 1:2 ratio, to receive maintenance dosing every 4 weeks or every 8 weeks to week 48. The primary end point was 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16. The primary analysis was first tested for the noninferiority of bimekizumab to secukinumab at a margin of -10 percentage points and then tested for superiority.
Results: A total of 1005 patients were screened and 743 were enrolled; 373 patients were assigned to receive bimekizumab and 370 to receive secukinumab. At week 16, a total of 230 patients (61.7%) in the bimekizumab group and 181 (48.9%) in the secukinumab group had a 100% reduction from baseline in the PASI score (PASI 100) (adjusted risk difference, 12.7 percentage points; 95% confidence interval [CI], 5.8 to 19.6); bimekizumab was shown to be noninferior and superior to secukinumab (P<0.001 for noninferiority and superiority). At week 48, a total of 250 patients (67.0%) treated with bimekizumab had a PASI 100 response, as compared with 171 patients (46.2%) treated with secukinumab (adjusted risk difference, 20.9 percentage points; 95% CI, 14.1 to 27.7; P<0.001). At the week 4 time point, 265 patients (71.0%) in the bimekizumab group had 75% or greater reduction from baseline in the PASI score, as compared with 175 patients (47.3%) in the secukinumab group (adjusted risk difference, 23.7; 95% CI, 17.0 to 30.4; P<0.001). Oral candidiasis occurred more often with bimekizumab (72 patients, 19.3%) than with secukinumab (11 patients, 3.0%).
Conclusions: In patients with moderate-to-severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks but was associated with oral candidiasis (predominantly mild or moderate as recorded by the investigator). Longer and larger trials are required to determine the comparative effect and risks of interleukin-17 inhibitors in psoriasis. (Funded by UCB Pharma; BE RADIANT ClinicalTrials.gov number, NCT03536884.).
Secukinumab: A Review in Ankylosing Spondylitis
Drugs2019 Mar;79(4):433-443.PMID: 30793255DOI: 10.1007/s40265-019-01075-3
Secukinumab (Cosentyx®), a first-in-class fully human monoclonal antibody against interleukin-17A, is approved in several countries, including the USA and those of the EU, for the treatment of ankylosing spondylitis (AS). Subcutaneous secukinumab significantly improved the clinical signs and symptoms of AS versus placebo in three of four phase III trials. The benefits of secukinumab were generally seen regardless of whether patients had or had not received previous tumour necrosis factor (TNF) inhibitor therapy, and were sustained during longer-term (up to 5 years) treatment. Secukinumab was also associated with improvements in spinal mobility, physical function, health-related quality of life and work productivity in some of the trials. In MEASURE 1, secukinumab reduced inflammation in the sacroiliac joint, and slowed radiographic progression. Secukinumab was generally well tolerated during up to 5 years' treatment; the most commonly reported adverse event was nasopharyngitis. In the minority of patients who developed anti-drug antibodies (ADAs), ADAs did not decrease efficacy or increase adverse events. In conclusion, secukinumab is an effective therapy for TNF inhibitor-naive patients with active AS, and provides a useful treatment option for patients who have an inadequate response to or are intolerant of TNF inhibitors.
Secukinumab in plaque psoriasis--results of two phase 3 trials
N Engl J Med2014 Jul 24;371(4):326-38.PMID: 25007392DOI: 10.1056/NEJMoa1314258
Background: Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.
Methods: In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points).
Results: The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept.
Conclusions: Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).
Safety of secukinumab in the treatment of psoriasis
Expert Opin Drug Saf2016 Oct;15(10):1413-20.PMID: 27545070DOI: 10.1080/14740338.2016.1221923
Introduction: Secukinumab is a human monoclonal antibody that selectively targets and neutralizes interleukin (IL)-17A, a cytokine that is normally involved in mucocutaneous defense against extracellular organisms and is abnormally expressed in psoriasis. In 2015, secukinumab was the first IL-17A inhibitor approved for the treatment of moderate-to-severe psoriasis.
Areas covered: This review evaluates the safety profile of secukinumab for the treatment of moderate-to-severe psoriasis and its role in the clinical landscape. A literature search was performed for articles published through February 2016; additional data from a pooled safety analysis of 10 Phase II and III secukinumab studies were reviewed.
Expert opinion: Collectively, these studies show that secukinumab demonstrates a highly favorable safety profile, especially compared with commonly used psoriasis treatments such as methotrexate and TNF-α blockers. More specifically, secukinumab carries no increased risks for end-organ toxicities, serious infection, multiple sclerosis, reactivation of latent tuberculosis or hepatitis B, leukemia/lymphoma, and nonmelanoma skin cancer. Mucocutaneous candidiasis is a common side effect and occurs at a rate of 3.55/100 subject-years with secukinumab 300 mg, yet these infections usually do not interfere with maintenance of secukinumab therapy. The combination of proven efficacy and safety make secukinumab an excellent new treatment choice for individuals with moderate-to-severe psoriasis.
Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial
Lancet2020 May 9;395(10235):1496-1505.PMID: 32386593DOI: 10.1016/S0140-6736(20)30564-X
Background: Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response.
Methods: This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080.
Findings: Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator.
Interpretation: Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis.
Funding: Novartis Pharma.