Nirsevimab API Manufacturers

General Description:

Nirsevimab, identified by CAS number 1989556-22-0, is a notable compound with significant therapeutic applications. Nirsevimab (MEDI8897) is a recombinant human immunoglobulin G1 kappa (IgG1ĸ) monoclonal antibody used to prevent respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants. It binds to the prefusion conformation of the RSV F protein, a glycoprotein involved in the membrane fusion step of the viral entry process, and neutralizes several RSV A and B strains. Compared to , another anti-RSV antibody, nirsevimab shows greater potency at reducing pulmonary viral loads in animal models. In addition, nirsevimab was developed as a single-dose treatment for all infants experiencing their first RSV season, whereas palivizumab requires five monthly doses to cover an RSV season. This is due to a modification in the Fc region of nirsevimab that grants it a longer half-time compared to typical monoclonal antibodies. On November 2022, nirsevimab was approved by the EMA for the prevention of RSV lower respiratory tract disease in newborns and infants during their first RSV season.

Indications:

This drug is primarily indicated for: Nirsevimab is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Nirsevimab undergoes metabolic processing primarily in: As a monoclonal antibody, nirsevimab is expected to be metabolized by proteases throughout the body. It is not metabolized by hepatic enzymes. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Nirsevimab are crucial for its therapeutic efficacy: At clinically relevant intramuscular doses (25-300 mg) in infants and adults, nirsevimab follows dose-proportional pharmacokinetics, and it reaches maximum concentration within 6 days (range 1 to 28 days) following intramuscular administration. The estimated absolute bioavailability of nirsevimab was 85%. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Nirsevimab is an important consideration for its dosing schedule: The terminal half-life of nirsevimab was approximately 69 days. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Nirsevimab from the body primarily occurs through: As a monoclonal antibody, nirsevimab is eliminated by intracellular catabolism. At clinical doses, there is no evidence of target-mediated clearance. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Nirsevimab is distributed throughout the body with a volume of distribution of: For an infant weighing 5 kg, nirsevimab has a central and peripheral volume of distribution of 249 mL and 241 mL, respectively. The volume of distribution of nirsevimab increases with body weight. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Nirsevimab is a critical factor in determining its safe and effective dosage: For an infant weighing 5 kg, nirsevimab has an estimated clearance of 3.38 mL/day. The clearance of nirsevimab increases with body weight. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Nirsevimab exerts its therapeutic effects through: A phase 1b/2a dose-escalation study that included healthy preterm infants with a gestational age of 32–35 weeks observed that, at day 8 after dosing, more than 95% of infants treated with nirsevimab had RSV-neutralizing antibody levels higher than 4-fold rise from baseline, and that the RSV-neutralizing antibody levels persisted in infants treated with 50mg of nirsevimab at day 151. Furthermore, RSV-neutralizing antibody levels correlated with nirsevimab serum concentrations. A study that evaluated the efficacy of nirsevimab in healthy preterm infants reported that a single injection led to less medically attended RSV-associated lower respiratory tract infections. Similar results were reported in another study that included healthy late-preterm and term infants. The use of nirsevimab may lead to serious hypersensitivity reactions, including anaphylaxis. Similar to other intramuscular injections, nirsevimab should be given with caution to infants with thrombocytopenia or other coagulation disorders. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Nirsevimab functions by: Nirsevimab is a recombinant human immunoglobulin G1 kappa (IgG1ĸ) long-acting monoclonal antibody that binds to the prefusion conformation of the respiratory syncytial virus (RSV) F protein. RSV is coated with two types of glycoproteins, the attachment glycoprotein (G protein) and the fusion glycoprotein (F protein). Of these two, only the F protein is essential for the entry of the virus into cells lining the respiratory tract, making it a desirable drug target. The RSV F protein is initially in a metastable prefusion conformation and undergoes conformational changes after being triggered by an unknown event. These conformational changes lead to a postfusion conformation, where both viral and host-cell membranes are together. Nirsevimab binds to a highly conserved epitope of the RSV prefusion F protein, inhibiting the membrane fusion step in the viral entry process. This allows nirsevimab to neutralize various RSV A and B strains and block cell-to-cell fusion. Nirsevimab has also been modified with a triple amino acid substitution (M257Y/S259T/T261E ) in the Fc region to extend serum half-life from the typical 21–28 days to approximately 69 days. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Nirsevimab 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:

Nirsevimab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, Proteins, Respiratory Syncytial Virus Anti-F Protein Monoclonal Antibody, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Nirsevimab include:

• Molecular Weight: 146300.0
• Molecular Formula: C6494H10060N1708O2050S46