Anifrolumab
目录号 : GC68343Anifrolumab 是一种 I 型干扰素 (IFN) 受体拮抗剂，是一种人源单克隆抗体。Anifrolumab 能阻断 I 型干扰素的活性，可用于系统性红斑狼疮 (SLE) 的研究。
Cas No.:1326232-46-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- COA (Certificate Of Analysis)
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- Datasheet
Anifrolumab is a type I interferon (IFN) receptor antagonist, a human monoclonal antibody. Anifrolumab blocks the activity of type I interferon. Anifrolumab can be used in systemic lupus erythematosus (SLE) research[1][2].
Anifrolumab (67.7 nM; 20 min) induces sustained reduction of surface IFNAR1 and abrogates STAT1 phosphorylation[2].
Anifrolumab (1 and 10 μg/mL; 6 or 7 d) suppresses differentiation of B cells into plasma cells[2].
Anifrolumab inhibits type I IFN-induced ISRE signaling, with IC50s ranging from 0.004 to 0.3 nM for the IFN-α subtypes, and 0.03 nM and 0.07 nM for IFN-β and IFN-ω, respectively[2].
Anifrolumab (67.7 nM) dose-dependently inhibits IFN-α production from pDCs in response to CpG-A or DNA-IC stimulation, inhibiting 87-95% of IFN-α production[2].
Western Blot Analysis[2]
| Cell Line: | Peripheral blood mononuclear cells (PBMCs) |
| Concentration: | 67.7 nM |
| Incubation Time: | 20 min |
| Result: | Abrogated IFN-α2-dependent and pDC supernatant-dependent STAT1 phosphorylation. |
Cell Differentiation Assay[2]
| Cell Line: | Plasmacytoid dendritic cell (pDC) |
| Concentration: | 1 and 10 μg/mL |
| Incubation Time: | 6 or 7 days |
| Result: | Inhibited pDC-mediated plasma cell differentiation in a dose-dependent manner, with a mean 76% reduction in plasma cell number relative to control antibody. |
[1]. Furie R, et al. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386.
[2]. Riggs JM, et al. Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Lupus Sci Med. 2018 Apr 5;5(1):e000261.
| Cas No. | 1326232-46-5 | SDF | Download SDF |
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
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Trial of Anifrolumab in Active Systemic Lupus Erythematosus
N Engl J Med 2020 Jan 16;382(3):211-221.PMID:31851795DOI:10.1056/NEJMoa1912196.
Background: Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point. Methods: We randomly assigned patients in a 1:1 ratio to receive intravenous Anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate. Results: A total of 362 patients received the randomized intervention: 180 received Anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the Anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P = 0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the Anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with Anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received Anifrolumab. There was one death from pneumonia in the Anifrolumab group. Conclusions: Monthly administration of Anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with Anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.).
Anifrolumab: First Approval
Drugs 2021 Oct;81(15):1795-1802.PMID:34554438DOI:10.1007/s40265-021-01604-z.
Anifrolumab (anifrolumab-fnia; Saphnelo™) is a monoclonal antibody antagonist of the type 1 interferon receptor (IFNAR). It is being developed by AstraZeneca (under license from Medarex, now Bristol-Myers Squibb) for the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE) and lupus nephritis, the underlying pathogenesis of which involves type 1 interferon. In July 2021, intravenous Anifrolumab was approved in the USA for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy. Anifrolumab (intravenous or subcutaneous) continues to be assessed in clinical studies in SLE in various countries, and the intravenous formulation is under regulatory review in the EU and Japan. This article summarizes the milestones in the development of Anifrolumab leading to this first approval for the treatment of moderate to severe SLE.
Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus
Arthritis Rheumatol 2017 Feb;69(2):376-386.PMID:28130918DOI:10.1002/art.39962.
Objective: To assess the efficacy and safety of Anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate-to-severe systemic lupus erythematosus (SLE). Methods: Patients (n = 305) were randomized to receive intravenous Anifrolumab (300 mg or 1,000 mg) or placebo, in addition to standard therapy, every 4 weeks for 48 weeks. Randomization was stratified by SLE Disease Activity Index 2000 score (<10 or ≥10), oral corticosteroid dosage (<10 or ≥10 mg/day), and type I IFN gene signature test status (high or low) based on a 4-gene expression assay. The primary end point was the percentage of patients achieving an SLE Responder Index (SRI[4]) response at week 24 with sustained reduction of oral corticosteroids (<10 mg/day and less than or equal to the dose at week 1 from week 12 through 24). Other end points (including SRI[4], British Isles Lupus Assessment Group [BILAG]-based Composite Lupus Assessment [BICLA], modified SRI[6], and major clinical response) were assessed at week 52. The primary end point was analyzed in the modified intent-to-treat (ITT) population and type I IFN-high subpopulation. The study result was considered positive if the primary end point was met in either of the 2 study populations. The Type I error rate was controlled at 0.10 (2-sided), within each of the 2 study populations for the primary end point analysis. Results: The primary end point was met by more patients treated with Anifrolumab (34.3% of 99 for 300 mg and 28.8% of 104 for 1,000 mg) than placebo (17.6% of 102) (P = 0.014 for 300 mg and P = 0.063 for 1,000 mg, versus placebo), with greater effect size in patients with a high IFN signature at baseline (13.2% in placebo-treated patients versus 36.0% [P = 0.004] and 28.2% [P = 0.029]) in patients treated with Anifrolumab 300 mg and 1,000 mg, respectively. At week 52, patients treated with Anifrolumab achieved greater responses in SRI(4) (40.2% versus 62.6% [P < 0.001] and 53.8% [P = 0.043] with placebo, Anifrolumab 300 mg, and Anifrolumab 1,000 mg, respectively), BICLA (25.7% versus 53.5% [P < 0.001] and 41.2% [P = 0.018], respectively), modified SRI(6) (28.4% versus 49.5% [P = 0.002] and 44.7% [P = 0.015], respectively), major clinical response (BILAG 2004 C or better in all organ domains from week 24 through week 52) (6.9% versus 19.2% [P = 0.012] and 17.3% [P = 0.025], respectively), and several other global and organ-specific end points. Herpes zoster was more frequent in the anifrolumab-treated patients (2.0% with placebo treatment versus 5.1% and 9.5% with Anifrolumab 300 mg and 1,000 mg, respectively), as were cases reported as influenza (2.0% versus 6.1% and 7.6%, respectively), in the Anifrolumab treatment groups. Incidence of serious adverse events was similar between groups (18.8% versus 16.2% and 17.1%, respectively). Conclusion: Anifrolumab substantially reduced disease activity compared with placebo across multiple clinical end points in the patients with moderate-to-severe SLE.
Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials
Mod Rheumatol 2021 Jan;31(1):1-12.PMID:32814461DOI:10.1080/14397595.2020.1812201.
Chronic activation of the type I interferon (IFN) pathway plays a critical role in systemic lupus erythematosus (SLE) pathogenesis. Anifrolumab is a human monoclonal antibody to the type I IFN receptor subunit 1, which blocks the action of type I IFNs. Two phase 3 studies (TULIP-1 and TULIP-2) and a phase 2b study (MUSE) provide substantial evidence for the efficacy and safety of Anifrolumab for moderately to severely active SLE. In all three studies, monthly intravenous Anifrolumab 300 mg was associated with treatment differences >16% compared with placebo at Week 52 in British Isles Lupus Assessment Group-based Composite Lupus Assessment response rates. The combined data across a range of other clinically significant endpoints (e.g. oral corticosteroid reduction, improved skin disease, flare reduction) further support the efficacy of Anifrolumab for SLE treatment. The safety profile of Anifrolumab was generally similar across all studies; serious adverse events occurred in 8-16% and 16-19% of patients receiving Anifrolumab and placebo, respectively. Herpes zoster incidence was greater with Anifrolumab (≤7%) vs placebo (≤2%). Evidence from these clinical trials suggests that in patients with active SLE, Anifrolumab is superior to placebo in achieving composite endpoints of disease activity response and oral corticosteroid reduction.
Anifrolumab reduces flare rates in patients with moderate to severe systemic lupus erythematosus
Lupus 2021 Jul;30(8):1254-1263.PMID:33977796DOI:10.1177/09612033211014267.
Background: Systemic lupus erythematosus (SLE) management objectives include preventing disease flares while minimizing glucocorticoid exposure. Pooled data from the phase 3 TULIP-1 and TULIP-2 trials in patients with moderate to severe SLE were analyzed to determine Anifrolumab's effect on flares, including those arising with glucocorticoid taper. Methods: TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous Anifrolumab (300 mg every 4 weeks for 48 weeks). For patients receiving baseline glucocorticoid ≥10 mg/day, attempted taper to ≤7.5 mg/day prednisone or equivalent from Weeks 8-40 was required and defined as sustained reduction when maintained through Week 52. Flares were defined as ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B scores versus the previous visit. Flare assessments were compared for patients receiving Anifrolumab versus placebo. Results: Compared with placebo (n = 366), Anifrolumab (n = 360) was associated with lower annualized flare rates (rate ratio 0.75, 95% confidence interval [CI] 0.60-0.95), prolonged time to first flare (hazard ratio 0.70, 95% CI 0.55-0.89), and fewer patients with ≥1 flare (difference -9.3%, 95% CI -16.3 to -2.3), as well as flares in organ domains commonly active at baseline (musculoskeletal, mucocutaneous). Fewer BILAG-based Composite Lupus Assessment responders had ≥1 flare with Anifrolumab (21.1%, 36/171) versus placebo (30.4%, 34/112). Of patients who achieved sustained glucocorticoid reductions from ≥10 mg/day at baseline, more remained flare free with Anifrolumab (40.0%, 76/190) versus placebo (17.3%, 32/185). Conclusions: Analyses of pooled TULIP-1 and TULIP-2 data support that Anifrolumab reduces flares while permitting glucocorticoid taper in patients with SLE.ClinicalTrials.gov identifiersTULIP-1 NCT02446912 (clinicaltrials.gov/ct2/show/NCT02446912);TULIP-2 NCT02446899 (clinicaltrials.gov/ct2/show/NCT02446899).