Nirsevimab
Identification
- Summary
Nirsevimab is a long-acting monoclonal antibody indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants.
- Brand Names
- Beyfortus
- Generic Name
- Nirsevimab
- DrugBank Accession Number
- DB16258
- Background
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.6 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.6,1 Compared to palivizumab, 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.5 This is due to a modification in the Fc region of nirsevimab that grants it a longer half-time compared to typical monoclonal antibodies.1,6
On November 2022, nirsevimab was approved by the EMA for the prevention of RSV lower respiratory tract disease in newborns and infants.6 Nirsevimab was also approved by Health Canada on April 19, 2023 and by the FDA in July 17, 2023 for the same indication.7,9
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6494H10060N1708O2050S46
- Protein Average Weight
- 146300.0 Da (approximate)
- Sequences
>Heavy_chain QVQLVQSGAEVKKPGSSVMVSCQASGGLLEDYIINWVRQAPGQGPEWMGGIIPVLGTVHY GPKFQGRVTITADESTDTAYMELSSLRSEDTAMYYCATETALVVSETYLPHYFDNWGQGT LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQDWLEGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light_chain DIQMTQSPSSLSAAVGDRVTITCQASQDIVNYLNWYQQKPGKAPKLLIYVASNLETGVPS RFSGSGSGTDFSLTISSLQPEDVATYYCQQYDNLPLTFGGGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- American Medical Association: Statement on a nonproprietary name adopted by the USAN council (nirsevimab) [Link]
- Synonyms
- Immunoglobulin g1-kappa, anti-(human respiratory syncytial virus fusion glycoprotein f0 (protein f))human monoclonal antibody.gamma.1 heavy chain (1-456) (human vh (homo sapiens ighv1-69*01(ighd)-ighj4*01 (90.1%)) (8.8.19) (1-126) -homo sapiens ighg1*03
- Immunoglobulin g1, anti-(human respiratory syncytial virus fusion protein)(human monoclonal med18897 .gamma.1-chain), disulfide with monoclonal med18897 .kappa.-chain, dimer
- Nirsevimab
- External IDs
- MED-18897
- MEDI8897
Pharmacology
- Indication
Nirsevimab is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season in Canada, the US, and Europe.6,7 Additionally, Nirsevimab is also approved in Canada and the US for use in infants up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.7,8 These infants include, but are not limited to, those with chronic lung disease of prematurity, hemodynamically significant congenital heart disease, immunocompromised states, Down syndrome, cystic fibrosis, neuromuscular disease, and congenital airway anomalies.7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prevention of Lower respiratory tract disease caused by respiratory syncytial virus (rsv) •••••••••••• •••••••• •••• •• •••••• •••••••• •••••••••• •••••••• ••••••••• Prevention of Lower respiratory tract disease caused by respiratory syncytial virus (rsv) •••••••••••• ••••••• •••••••• ••••••••• Prevention of Lower respiratory tract disease caused by respiratory syncytial virus (rsv) •••••••••••• •••••• •••• •• •••••• •••••••• •••••••••• •••••••• Prevention of Lower respiratory tract disease caused by respiratory syncytial virus (rsv) •••••••••••• ••••••• •••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
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.1 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.3 Similar results were reported in another study that included healthy late-preterm and term infants.4 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.6
- Mechanism of action
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.6,1 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.2
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 [YTE]) in the Fc region to extend serum half-life from the typical 21–28 days to approximately 69 days.6,1
Target Actions Organism AFusion glycoprotein F0 antibodyHuman respiratory syncytial virus B (strain 18537) AFusion glycoprotein F0 antibodyHuman respiratory syncytial virus A (strain A2) AFusion glycoprotein F0 antibodyHuman respiratory syncytial virus A (strain RSS-2) - Absorption
At clinically relevant intramuscular doses (25-300 mg) in infants and adults, nirsevimab follows dose-proportional pharmacokinetics,1,6 and it reaches maximum concentration within 6 days (range 1 to 28 days) following intramuscular administration. The estimated absolute bioavailability of nirsevimab was 85%.6
- Volume of distribution
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.6
- Protein binding
Not Available
- Metabolism
As a monoclonal antibody, nirsevimab is expected to be metabolized by proteases throughout the body. It is not metabolized by hepatic enzymes.6
- Route of elimination
As a monoclonal antibody, nirsevimab is eliminated by intracellular catabolism. At clinical doses, there is no evidence of target-mediated clearance.6
- Half-life
The terminal half-life of nirsevimab was approximately 69 days.6
- Clearance
For an infant weighing 5 kg, nirsevimab has an estimated clearance of 3.38 mL/day. The clearance of nirsevimab increases with body weight.6
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
A specific nirsevimab overdose treatment is not available. In the event of an overdose, the individual should be monitored for the occurrence of adverse reactions and provided with symptomatic treatment as appropriate. Preclinical studies of safety pharmacology, repeated dose toxicity and tissue cross-reactivity, did not reveal nirsevimab as a special hazard for humans.6
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareImlifidase The therapeutic efficacy of Nirsevimab can be decreased when used in combination with Imlifidase. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Beyfortus (AstraZeneca AB)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Beyfortus Solution 50 mg / 0.5 mL Intramuscular Sanofi Pasteur Limited Not applicable Not applicable Canada Beyfortus Injection 100 mg/1mL Intramuscular Sanofi Pasteur Inc. 2023-07-18 Not applicable US Beyfortus Solution 100 mg / 1 mL Intramuscular Sanofi Pasteur Limited Not applicable Not applicable Canada Beyfortus Injection 50 mg/0.5mL Intramuscular Sanofi Pasteur Inc. 2023-07-18 Not applicable US
Categories
- ATC Codes
- J06BD08 — Nirsevimab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antiinfectives for Systemic Use
- Antiviral monoclonal antibodies
- Blood Proteins
- Globulins
- Immune Sera and Immunoglobulins
- Immunoglobulins
- Immunoproteins
- Proteins
- Respiratory Syncytial Virus Anti-F Protein Monoclonal Antibody
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- VRN8S9CW5V
- CAS number
- 1989556-22-0
References
- Synthesis Reference
Khan, AA et al. (2020) Dosage regimens for and compositions including anti-rsv antibodies. (U.S. Patent No. 2020/0347120 A1). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/6b/d2/10/a841b66e0c90cf/US20200347120A1.pdf
- General References
- Domachowske JB, Khan AA, Esser MT, Jensen K, Takas T, Villafana T, Dubovsky F, Griffin MP: Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants. Pediatr Infect Dis J. 2018 Sep;37(9):886-892. doi: 10.1097/INF.0000000000001916. [Article]
- Battles MB, Langedijk JP, Furmanova-Hollenstein P, Chaiwatpongsakorn S, Costello HM, Kwanten L, Vranckx L, Vink P, Jaensch S, Jonckers TH, Koul A, Arnoult E, Peeples ME, Roymans D, McLellan JS: Molecular mechanism of respiratory syncytial virus fusion inhibitors. Nat Chem Biol. 2016 Feb;12(2):87-93. doi: 10.1038/nchembio.1982. Epub 2015 Dec 7. [Article]
- Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, Simoes EAF, Esser MT, Khan AA, Dubovsky F, Villafana T, DeVincenzo JP: Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. N Engl J Med. 2020 Jul 30;383(5):415-425. doi: 10.1056/NEJMoa1913556. [Article]
- Hammitt LL, Dagan R, Yuan Y, Baca Cots M, Bosheva M, Madhi SA, Muller WJ, Zar HJ, Brooks D, Grenham A, Wahlby Hamren U, Mankad VS, Ren P, Takas T, Abram ME, Leach A, Griffin MP, Villafana T: Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med. 2022 Mar 3;386(9):837-846. doi: 10.1056/NEJMoa2110275. [Article]
- Venkatesan P: Nirsevimab: a promising therapy for RSV. Lancet Microbe. 2022 May;3(5):e335. doi: 10.1016/S2666-5247(22)00097-0. [Article]
- EMA Summary of Product Characteristics: Beyfortus (nirsevimab) solution for injection [Link]
- Health Canada Approved Drug Products: BEYFORTUS (nirsevimab) Intramuscular Injection [Link]
- FDA Approved Drug Products: BEYFORTUS (nirsevimab-alip) injection, for intramuscular use [Link]
- Press Release: FDA approves Beyfortus™ (nirsevimab-alip) to protect infants against RSV disease [Link]
- External Links
- 2642401
- Wikipedia
- Nirsevimab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Prevention Healthy Volunteers (HV) / RSV Immunization 1 3 Active Not Recruiting Prevention Respiratory Syncytial Virus (RSV) Infection 2 3 Completed Prevention Respiratory Syncytial Virus (RSV) Infection 1 3 Recruiting Prevention Lower Respiratory Tract Infection (LRTI) 1 2 Completed Prevention Respiratory Syncytial Virus (RSV) Infection 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intramuscular 100 mg/1mL Injection Intramuscular 50 mg/0.5mL Injection, solution Intramuscular 100 mg Injection, solution Intramuscular 50 mg Solution Intramuscular 100 mg / 1 mL Solution Intramuscular 50 mg / 0.5 mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Human respiratory syncytial virus B (strain 18537)
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Not Available
- Specific Function
- During virus entry, induces fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. The fusogenic activity is inactive untill entry into host cell endosom...
- Gene Name
- F
- Uniprot ID
- P13843
- Uniprot Name
- Fusion glycoprotein F0
- Molecular Weight
- 63687.815 Da
References
- Domachowske JB, Khan AA, Esser MT, Jensen K, Takas T, Villafana T, Dubovsky F, Griffin MP: Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants. Pediatr Infect Dis J. 2018 Sep;37(9):886-892. doi: 10.1097/INF.0000000000001916. [Article]
- EMA Summary of Product Characteristics: Beyfortus (nirsevimab) solution for injection [Link]
- Kind
- Protein
- Organism
- Human respiratory syncytial virus A (strain A2)
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Fusion glycoprotein F0 Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins.
- Specific Function
- Identical protein binding
- Gene Name
- F
- Uniprot ID
- P03420
- Uniprot Name
- Fusion glycoprotein F0
- Molecular Weight
- 63452.745 Da
References
- Domachowske JB, Khan AA, Esser MT, Jensen K, Takas T, Villafana T, Dubovsky F, Griffin MP: Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants. Pediatr Infect Dis J. 2018 Sep;37(9):886-892. doi: 10.1097/INF.0000000000001916. [Article]
- EMA Summary of Product Characteristics: Beyfortus (nirsevimab) solution for injection [Link]
- Kind
- Protein
- Organism
- Human respiratory syncytial virus A (strain RSS-2)
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Fusion glycoprotein F0 Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins.
- Specific Function
- Not Available
- Gene Name
- F
- Uniprot ID
- P11209
- Uniprot Name
- Fusion glycoprotein F0
- Molecular Weight
- 63333.525 Da
References
- Domachowske JB, Khan AA, Esser MT, Jensen K, Takas T, Villafana T, Dubovsky F, Griffin MP: Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants. Pediatr Infect Dis J. 2018 Sep;37(9):886-892. doi: 10.1097/INF.0000000000001916. [Article]
- EMA Summary of Product Characteristics: Beyfortus (nirsevimab) solution for injection [Link]
Drug created at December 15, 2020 18:17 / Updated at July 25, 2023 16:37