NAV

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
References:
  1. American Medical Association: Statement on a nonproprietary name adopted by the USAN council (nirsevimab) [Link]
Download FASTA Format
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
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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

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofLower respiratory tract disease caused by respiratory syncytial virus (rsv)•••••••••••••••••••••••• •• •••••• •••••••• •••••••••• •••••••••••••••••
Prevention ofLower respiratory tract disease caused by respiratory syncytial virus (rsv)••••••••••••••••••• •••••••••••••••••
Prevention ofLower respiratory tract disease caused by respiratory syncytial virus (rsv)•••••••••••••••••••••• •• •••••• •••••••• •••••••••• ••••••••
Prevention ofLower respiratory tract disease caused by respiratory syncytial virus (rsv)••••••••••••••••••• •••••••••••••••••
Contraindications & Blackbox Warnings
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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

TargetActionsOrganism
AFusion glycoprotein F0
antibody
Human respiratory syncytial virus B (strain 18537)
AFusion glycoprotein F0
antibody
Human respiratory syncytial virus A (strain A2)
AFusion glycoprotein F0
antibody
Human 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
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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.
DrugInteraction
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ImlifidaseThe therapeutic efficacy of Nirsevimab can be decreased when used in combination with Imlifidase.
Food Interactions
No interactions found.

Products

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International/Other Brands
Beyfortus (AstraZeneca AB)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BeyfortusSolution50 mg / 0.5 mLIntramuscularSanofi Pasteur LimitedNot applicableNot applicableCanada flag
BeyfortusInjection100 mg/1mLIntramuscularSanofi Pasteur Inc.2023-07-18Not applicableUS flag
BeyfortusSolution100 mg / 1 mLIntramuscularSanofi Pasteur LimitedNot applicableNot applicableCanada flag
BeyfortusInjection50 mg/0.5mLIntramuscularSanofi Pasteur Inc.2023-07-18Not applicableUS flag

Categories

ATC Codes
J06BD08 — Nirsevimab
Drug Categories
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Venkatesan P: Nirsevimab: a promising therapy for RSV. Lancet Microbe. 2022 May;3(5):e335. doi: 10.1016/S2666-5247(22)00097-0. [Article]
  6. EMA Summary of Product Characteristics: Beyfortus (nirsevimab) solution for injection [Link]
  7. Health Canada Approved Drug Products: BEYFORTUS (nirsevimab) Intramuscular Injection [Link]
  8. FDA Approved Drug Products: BEYFORTUS (nirsevimab-alip) injection, for intramuscular use [Link]
  9. Press Release: FDA approves Beyfortus™ (nirsevimab-alip) to protect infants against RSV disease [Link]
RxNav
2642401
Wikipedia
Nirsevimab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingPreventionHealthy Volunteers (HV) / RSV Immunization1
3Active Not RecruitingPreventionRespiratory Syncytial Virus (RSV) Infection2
3CompletedPreventionRespiratory Syncytial Virus (RSV) Infection1
3RecruitingPreventionLower Respiratory Tract Infection (LRTI)1
2CompletedPreventionRespiratory Syncytial Virus (RSV) Infection2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntramuscular100 mg/1mL
InjectionIntramuscular50 mg/0.5mL
Injection, solutionIntramuscular100 mg
Injection, solutionIntramuscular50 mg
SolutionIntramuscular100 mg / 1 mL
SolutionIntramuscular50 mg / 0.5 mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Details1. Fusion glycoprotein F0
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
  1. 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]
  2. EMA Summary of Product Characteristics: Beyfortus (nirsevimab) solution for injection [Link]
Details2. Fusion glycoprotein F0
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
  1. 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]
  2. EMA Summary of Product Characteristics: Beyfortus (nirsevimab) solution for injection [Link]
Details3. Fusion glycoprotein F0
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
  1. 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]
  2. 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