Anifrolumab Overview

Introduction of Anifrolumab

Anifrolumab (also known as MEDI546) is a fully human, effector-null, IgG1κ monoclonal antibody (mAb) developed by MedImmune. It binds to interferon (IFN) alpha receptors 1 (IFNAR1) and blocks type I IFN signalling. Anifrolumab is currently in clinical development for treatment of systemic lupus erythematosus (SLE) and lupus nephritis. In the Phase IIb MUSE trial (NCT01438489), anifrolumab 300 mg every 4 weeks intravenously plus standard of care significantly decreased SLE disease activity across a range of endpoints, especially for patients with type I IFN gene signature test high results at baseline. Two Phase III trials (TULIP-I/II; NCT02446899/NCT02446912) are currently ongoing to further evaluate the efficacy and safety of intravenous anifrolumab for patients with moderate to severe SLE. Of the three novel anti-type type I IFN pathway antibodies (rontalizumab, sifalimumab and anifrolumab) evaluated in Phase II clinical trials for SLE, the intravenous formulation of anifrolumab had the highest efficacy relative to placebo.

Mechanism of Action of Anifrolumab

SLE is a chronic, multisystem autoimmune disease characterized by reoccurring flares and remissions. A growing body of evidence supports the roles of type I IFNs in the immunopathogenesis of SLE and other interferonopathies. Multiple genetic polymorphisms increase type I IFN signalling and are associated with increased susceptibility to SLE. Increased type I IFN expression and type I IFN-induced cell signalling correlate with SLE severity, and therapeutic use of type I IFNs for patients with viral hepatitis can induce a lupus-like syndrome. The family of type I IFNs includes IFN-α subtypes, IFN-β, IFN-δ, IFN-ε, IFN-κ and IFN-ω. type I IFN and the IFN alpha receptors 1 (IFNAR1) and 2 (IFNAR2) form a functional IFNAR complex, leading to tyrosine phosphorylation of signal transducer and activator of transcription 1 (STAT1) and 2 (STAT2). Phosphorylated STAT1 and STAT2 translocate with IFN regulatory factor 9 (IRF9) to the nucleus and drive IFN-stimulated response element (ISRE) activation. ISRE promotes transcription of multiple IFN-stimulated genes, which leads to the production of hundreds of proinflammatory and immunomodulatory proteins involved in the host innate immune response to viral infection. IFNAR activation also mediates cell-intrinsic induction of ISRE to produce more type I IFN and thereby autoamplify the IFN response. Thus, in autoimmune diseases, immune cells can rapidly produce large amounts of IFN at localized sites that ultimately can lead to tissue damage and disease exacerbation. Medicines targeting the type I IFN pathway may provide a therapeutic benefit in SLE and other diseases with a prominent type I IFN gene signature. Anifrolumab was designed to target IFNAR1 and blocks the type I IFN signalling. On the other, anifrolumab was engineered with a triple mutation L234F/L235E/P331S in the heavy chain to reduce engagement with the cell surface Fc gamma receptor (FcγR) and potential Fc-mediated effector function, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Mechanism of action of anifrolumab Fig.1 Mechanism of action of anifrolumab

Clinical Projects of Anifrolumab*

NCT ID Status Conditions Lead Sponsor Update Time
NCT02547922 Recruiting Lupus Nephritis AstraZeneca September 14, 2015
NCT03435601 Recruiting Rheumatoid Arthritis Josef Smolen, Univ. Prof. Dr. February 16, 2018
NCT02794285 Recruiting Active Systemic Lupus Erythematosus AstraZeneca June 9, 2016
NCT02446899 Active, not recruiting Active Systemic Lupus Erythematosus AstraZeneca May 18, 2015
NCT02446912 Active, not recruiting Active Systemic Lupus Erythematosus AstraZeneca May 18, 2015
NCT02962960 Active, not recruiting Systemic Lupus Erythematosus AstraZeneca November 15, 2016

What We Provide

Therapeutic Antibody

We provide high-quality for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Anifrolumab

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