Find, compare & contact
Anifrolumab API Manufacturers & Suppliers

General Description:

Anifrolumab, identified by CAS number 1326232-46-5, is a notable compound with significant therapeutic applications. Anifrolumab, or MEDI-546, is a type 1 interferon receptor (IFNAR) inhibiting IgG1κ monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus. The standard therapy for systemic lupus erythematosus consists of antimalarials like , glucocorticoids like , and disease modifying antirheumatic drugs like . Three monoclonal antibodies (anifrolumab, , and ) that target the type 1 interferon pathway entered clinical trials as potential treatments for systemic lupus erythematosus, but so far only anifrolumab has been approved. The design of early clinical trials of anti-interferon treatments such as anifrolumab, rontalizumab, and sifalimumab have come under criticism. The design of the clinical trials use different definitions of autoantibody positivity, making comparison between trials difficult; all trials involve large portions of patients also using corticosteroids, which may alter patient responses in the experimental and placebo groups; and patient populations were largely homogenous, which may have increased the odds of success of the trial. Anifrolumab has also been investigated for the treatment of Scleroderma. Anifrolumab was granted FDA approval on 30 July 2021.

Indications:

This drug is primarily indicated for: Anifrolumab is indicated in the treatment of adults with moderate to severe systemic lupus erythematosus. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Anifrolumab undergoes metabolic processing primarily in: Monoclonal antibodies are mainly catabolized to smaller oligopeptides and individual amino acids. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Anifrolumab are crucial for its therapeutic efficacy: A 300 mg intravenous dose reaches a mean C_max of 82.4 µg/mL, with a T_max of 0.03 days, and an AUC of 907 day\*µg/mL. A 300 mg subcutaneous dose reaches a mean C_max of 36.2 µg/mL, with a T_max of 4.1 days, and an AUC of 785 day\*µg/mL. A 600 mg subcutaneous dose reaches a mean C_max of 63.9 µg/mL, with a T_max of 7.0 days, and an AUC of 1828 day\*µg/mL. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Anifrolumab is an important consideration for its dosing schedule: The serum elimination half life anifrolumab in a phase 1 trial in patients with scleroderma was 0.84 days for a 0.1 mg/kg single dose, 1.24 days for a 0.3 mg/kg single dose, 2.96 days for a 1.0 mg/kg single dose, 4.07 days for a 3.0 mg/kg single dose, and 7.70 days for a 10.0 mg/kg single dose. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Anifrolumab from the body primarily occurs through: Monoclonal IgG is predominantly eliminated by catabolism to individual amino acids that are either recycled in the body or metabolized for energy. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Anifrolumab is distributed throughout the body with a volume of distribution of: The estimated volume of distribution of anifrolumab at steady state is 6.23 L for a 69.1 kg patient. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Anifrolumab is a critical factor in determining its safe and effective dosage: The estimated systemic clearance of anifrolumab is 0.193 L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Anifrolumab exerts its therapeutic effects through: Anifrolumab is a type 1 interferon receptor (IFNAR) inhibiting IgG1κ monoclonal antibody indicated in the treatment of adults with moderate to severe systemic lupus erythematosus. It has a long duration of action as it is given every 4 weeks. Patients should be counselled regarding the risks of serious infections, hypersensitivity reactions, and malignancies. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Anifrolumab functions by: Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple systems in the body. SLE may manifest as a rash on the skin, and can progress to life-threatening autoimmune reactions in the kidney or nervous system. Type 1 interferon pathway activation has been identified as a mediator of pathogenesis in SLE, and the level of type 1 interferon expression is correlated with severity of SLE. Activation of the type 1 interferon receptor (INFAR1) by interferons alpha, beta, epsilon, kappa, and omega lead to stimulation of gene transcription. Activation of INFAR1 and INFAR2 lead to phosphorylation of STAT1 and STAT2, which are translocated with interferon regulatory factor 9 (IRF9) to the cell nucleus to activate the interferon-stimulated response element (ISRE). Activation of ISRE leads to the expression of many proinflammatory and immunomodulatory proteins, as well as the activation of a positive feedback loop that produces more type 1 interferons. Interferon alpha stimulates monocytes to mature into myeloid dendritic cells that express self antigens. CD4+ and CD8+ T-cells, as well as B cells, that are autoreactive will respond to the self antigens and induce inflammmation and apoptosis in cells. This self-reactive immune response damages otherwise healthy tissue throughout the body. Anifrolumab is an immunoglobulin gamma 1 kappa (IgG1κ) monoclonal antibody that selectively binds to subunit 1 of INFAR1. The binding of anifrolumab to IFNAR1 inhibits the activity of the receptor, decreasing downstream signalling and gene transcription of inflammatory mediators. The Fc region of anifrolumab carries the triple mutaion L234F/L235E/P331S to prevent binding of the Fc region of the antibody to cell surface Fc receptors. In a phase IIb clinical trial, the primary endpoint was reached by 34.3% of patients in the 300 mg treatment group, 28.8% of patients in the 1000 mg treatment group, and 17.6% of patients in the placebo group. Patients with higher interferon-stimulated gene transcription at baseline showed a greater response to treatment. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Anifrolumab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Anifrolumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antineoplastic and Immunomodulating Agents, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, Immunosuppressive Agents, Proteins, Selective Immunosuppressants, Serum Globulins, Type I Interferon Receptor Antagonist. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Anifrolumab include:

• Molecular Weight: 148000.0