Wikipedia

Nirsevimab

Nirsevimab, sold under the brand name Beyfortus, is a human recombinant monoclonal antibody with activity against respiratory syncytial virus (RSV).[10][11] It is a respiratory syncytial virus (RSV) F protein‑directed fusion inhibitor[6] that is designed to bind to the fusion protein on the surface of the RSV virus.[12][13]

Nirsevimab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetF protein of RSV
Clinical data
Trade namesBeyfortus
Other names
  • MEDI8897
  • nirsevimab-alip
AHFS/Drugs.comMicromedex Detailed Consumer Information
License data
Pregnancy
category
Routes of
administration		Intramuscular
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem SID
DrugBank
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6494H10060N1708O2050S46
Molar mass146336.58 g·mol−1

The most common side effects are rash, fever and injection site reactions (such as redness, swelling and pain where the injection is given).[8][14][15]

It was developed by AstraZeneca and Sanofi.[10][11] Nirsevimab was approved for medical use in both the European Union[9][16] and the United Kingdom in November 2022,[5] in Canada in April 2023,[2][17] and in the United States in July 2023.[15] Alternatively, in October 2023 the CDC recommended maternal RSVpreF vaccination during pregnancy, though both are not needed in most infants.

Medical uses

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In the European Union, nirsevimab is indicated for the prevention of respiratory syncytial virus RSV lower respiratory tract disease in neonates and infants during their first RSV season.[8]

In the United States, nirsevimab is indicated for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season and children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.[6][15] Alternatively, in October 2023 the CDC recommended maternal RSVpreF vaccination during pregnancy, though administration of both is not needed in most infants.[18]

Adverse effects

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No major hypersensitivity reactions have been reported, and adverse events of grade 3 or higher were only reported in 8% (77 of 968) of participants in clinical trial NCT02878330.[19][12]

Pharmacology

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Mechanism of action

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Nirsevimab binds to the prefusion conformation of the RSV fusion (F) protein, i.e. it binds to the site at which the virus would attach to a cell; effectively rendering it useless. It has a modified Fc region, extending the half-life of the drug in order for it to last the whole RSV season.[12]

History

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The opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) was based on data from two randomized, double-blind, placebo-controlled multicenter clinical trials that investigated the efficacy and safety of nirsevimab in healthy preterm (premature) and full-term infants entering their first RSV season.[14] These studies demonstrated that nirsevimab prevents lower respiratory tract infection caused by RSV requiring medical attention (such as bronchiolitis and pneumonia) in term and preterm infants during their first RSV season.[14]

The safety of nirsevimab was also evaluated in a phase II/III, randomized, double‑blind, multicenter trial in infants who were born five or more weeks prematurely (less than 35 weeks gestation) at higher risk for severe RSV disease and infants with chronic lung disease of prematurity (i.e. long-term respiratory problems faced by babies born prematurely) or congenital heart disease.[14] The results of this study showed that nirsevimab had a similar safety profile compared to palivizumab (Synagis).[14]

The US Food and Drug Administration (FDA) evaluated the safety and efficacy of nirsevimab based on three trials, two of which were randomized, double-blind, placebo-controlled, multicenter clinical trials (Trials 03, 04 and 05).[15] The key measure of efficacy was the incidence of medically attended RSV lower respiratory tract infection (MA RSV LRTI), evaluated during the 150 days after nirsevimab administration.[15] MA RSV LRTI included all health care provider visits (physician office, urgent care, emergency room visits and hospitalization) for lower respiratory tract disease with worsening clinical severity and a positive RSV test.[15]

Trial 03 included 1,453 preterm infants (born at greater than or equal to 29 weeks of gestational age up to less than 35 weeks of gestation) who were born during or entering their first RSV season.[15] Of the 1,453 preterm infants in the trial, 969 received a single dose of nirsevimab and 484 received placebo.[15] Among infants who were treated with nirsevimab, 25 (2.6%) experienced MA RSV LRTI compared with 46 (9.5%) infants who received placebo.[15] nirsevimab reduced the risk of MA RSV LRTI by approximately 70% relative to placebo.[15]

For Trial 04, the primary analysis group within the trial included 1,490 term and late preterm infants (born at greater than or equal to 35 weeks in gestational age), 994 of whom received a single dose of nirsevimab and 496 of whom received placebo.[15] Among infants who were treated with nirsevimab, 12 (1.2%) experienced MA RSV LRTI compared with 25 (5.0%) infants who received placebo.[15] Nirsevimab reduced the risk of MA RSV LRTI by approximately 75% relative to placebo.[15]

Trial 05, a randomized, double-blind, active (palivizumab)-controlled, multicenter trial, supported the use of nirsevimab in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.[15] The trial enrolled 925 preterm infants and infants with chronic lung disease of prematurity or congenital heart disease.[15] The safety and pharmacokinetic data from Trial 05 provided evidence for the use of nirsevimab to prevent MA RSV LRTI in this population.[15]

The FDA granted the application for nirsevimab a fast track designation.[15] and granted approval of Beyfortus to AstraZeneca.[15]

Society and culture

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On 15 September 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended to grant a marketing authorization for Beyfortus for the prevention of RSV lower respiratory tract disease in newborns and infants.[20][14] Beyfortus was reviewed under EMA's accelerated assessment program.[20] The applicant for this medicinal product is AstraZeneca AB.[20] In November 2022, nirsevimab was approved for medical use in the European Union,[9][16] and the United Kingdom.[21] It was approved in Canada in April 2023,[2][17] and in the United States in July 2023.[15]

Research

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As of 2022, nirsevimab was investigated as an experimental passive immunization agent (different to active immunization agents, such as vaccines) against RSV in the general infant population.[10][11] The MELODY study is an ongoing, randomized, double-blind, placebo-controlled to evaluate the safety and efficacy of nirsevimab in late preterm and term infants. Initial results were promising, with nirsevimab reducing LRTI (lower respiratory tract infections) by 74.5% compared to placebo in infants born at term or late preterm.[13][22][23]

As of April 2023, ongoing trials for nirsevimab were:

References

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  1. ^ a b "Beyfortus APMDS". Therapeutic Goods Administration (TGA). 8 December 2023. Archived from the original on 7 March 2024. Retrieved 7 March 2024.
  2. ^ a b c "Beyfortus Product information". Health Canada. 22 October 2009. Archived from the original on 8 August 2023. Retrieved 7 August 2023.
  3. ^ "Summary Basis of Decision for Beyfortus". Health Canada. 7 June 2023. Archived from the original on 12 January 2024. Retrieved 20 August 2023.
  4. ^ "Details for: Beyfortus". Health Canada. 19 April 2023. Archived from the original on 3 March 2024. Retrieved 20 August 2023.
  5. ^ a b "Respiratory syncytial virus (RSV) immunisation programme: JCVI advice, 7 June 2023". Medicines and Healthcare products Regulatory Agency (MHRA). 22 June 2023. Archived from the original on 11 July 2023. Retrieved 7 August 2023.
  6. ^ a b c "Beyfortus- nirsevimab injection". DailyMed. 17 July 2023. Archived from the original on 7 August 2023. Retrieved 6 August 2023.
  7. ^ "Press Release: U.S. CDC Advisory Committee unanimously recommends routine use of Beyfortus (nirsevimab-alip) to protect infants against RSV disease" (Press release). Sanofi - Aventis Groupe. 3 August 2023. Archived from the original on 8 August 2023. Retrieved 7 August 2023 – via GlobeNewswire News Room.
  8. ^ a b c "Beyfortus EPAR". European Medicines Agency. 23 June 2023. Archived from the original on 1 August 2023. Retrieved 6 August 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. ^ a b c "Beyfortus Product information". Union Register of medicinal products. 3 November 2022. Archived from the original on 6 November 2022. Retrieved 6 November 2022.
  10. ^ a b c "Nirsevimab demonstrated protection against respiratory syncytial virus disease in healthy infants in Phase 3 trial" (Press release). Sanofi. 26 April 2021. Archived from the original on 27 December 2021. Retrieved 27 December 2021.
  11. ^ a b c "Nirsevimab MELODY Phase III trial met primary endpoint of reducing RSV lower respiratory tract infections in healthy infants" (Press release). AstraZeneca. 26 April 2021. Archived from the original on 26 December 2021. Retrieved 27 December 2021.
  12. ^ a b c Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, et al. (Nirsevimab Study Group) (July 2020). "Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants". The New England Journal of Medicine. 383 (5): 415–425. doi:10.1056/NEJMoa1913556. PMID 32726528. S2CID 220876651.
  13. ^ a b Hammitt LL, Dagan R, Yuan Y, Baca Cots M, Bosheva M, Madhi SA, et al. (March 2022). "Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants". The New England Journal of Medicine. 386 (9): 837–846. doi:10.1056/NEJMoa2110275. PMID 35235726. S2CID 247220023.
  14. ^ a b c d e f "New medicine to protect babies and infants from respiratory syncytial virus (RSV) infection". European Medicines Agency (EMA) (Press release). 16 September 2022. Archived from the original on 19 September 2022. Retrieved 18 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  15. ^ a b c d e f g h i j k l m n o p q r s "FDA Approves New Drug to Prevent RSV in Babies and Toddlers" (Press release). U.S. Food and Drug Administration (FDA). Archived from the original on 19 July 2023. Retrieved 19 July 2023.   This article incorporates text from this source, which is in the public domain.
  16. ^ a b "Beyfortus approved in the EU for the prevention of RSV lower respiratory tract disease in infants". AstraZeneca (Press release). 4 November 2022. Archived from the original on 6 November 2022. Retrieved 6 November 2022.
  17. ^ a b "Health Canada approves new antibody drug to help prevent serious RSV in babies". CTVNews. 22 April 2023. Archived from the original on 24 April 2023. Retrieved 24 April 2023.
  18. ^ Fleming-Dutra, Katherine E. (6 October 2023). "Use of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the Prevention of Respiratory Syncytial Virus–Associated Lower Respiratory Tract Disease in Infants: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023". MMWR. Morbidity and Mortality Weekly Report. 72 (41): 1115–1122. doi:10.15585/mmwr.mm7241e1. ISSN 0149-2195. PMC 10578951. PMID 37824423.
  19. ^ Clinical trial number NCT02878330 at ClinicalTrials.gov
  20. ^ a b c "Beyfortus: Pending EC decision". European Medicines Agency (EMA). 15 September 2022. Archived from the original on 19 September 2022. Retrieved 18 September 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  21. ^ "MHRA Grants Approval of Beyfortus (nirsevimab) for Prevention of RSV Disease in Infants" (Press release). Sanofi. 9 November 2022. Archived from the original on 13 April 2023. Retrieved 13 April 2023 – via BusinessWire.
  22. ^ Zacks Equity Research (25 March 2022). "Pfizer's (PFE) RSV Jab Gets Another Breakthrough Therapy Tag". Nasdaq. Archived from the original on 8 April 2022. Retrieved 8 April 2022.
  23. ^ "Nirsevimab significantly protected infants against RSV disease in Phase III MELODY trial". AstraZeneca (Press release). 3 March 2022. Archived from the original on 27 October 2022. Retrieved 6 November 2022.
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