Nirsevimab, sold under the brand name Beyfortus, is a human recombinant

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

with activity against

respiratory syncytial virus Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. Its name is derive ...

(RSV). It is a respiratory syncytial virus (RSV) F protein‑directed

fusion inhibitor Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a Cell (biology), cell, for example, by blocking a Receptor (biochemistry), receptor. Entry inhibitors are used to treat condition ...

that is designed to bind to the

fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...

on the surface of the RSV virus. The most common side effects are rash, fever and

injection site reaction Injection site reactions (ISRs) are reactions that occur at the site of injection of a drug. They may be mild or severe and may or may not require medical intervention. Some reactions may appear immediately after injection, and some may be delayed ...

s (such as redness, swelling and pain where the injection is given). It was developed by

AstraZeneca AstraZeneca plc () (AZ) is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, UK. It has a portfolio of products for major diseases in areas includi ...

and

Sanofi Sanofi S.A. is a French Multinational corporation, multinational pharmaceutical and healthcare company headquartered in Paris, France. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 200 ...

. Nirsevimab was approved for medical use in both the European Union and the United Kingdom in November 2022, in Canada in April 2023, and in the United States in July 2023.

Medical uses

In the European Union, nirsevimab is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the prevention of

RSV lower respiratory tract disease in neonates and infants during their first RSV season. 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. Alternatively, in October 2023 the CDC recommended maternal RSVpreF vaccination during pregnancy, though administration of both is not needed in most infants.

Adverse effects

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.

Pharmacology

Mechanism of action

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 F_c region, extending the half-life of the drug in order for it to last the whole RSV season.

History

The opinion by the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

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. The studies demonstrated that nirsevimab prevents lower respiratory tract infection caused by RSV requiring medical attention (such as

bronchiolitis Bronchiolitis is inflammation of the small airways also known as the bronchioles in the lungs. Acute bronchiolitis is caused by a viral infection, usually affecting children younger than two years of age. Symptoms may include fever, cough, run ...

and

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

) in term and preterm infants during their first RSV season. The safety of nirsevimab was also evaluated in a phase II/III, randomized, double‑blind, multi-center 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 A congenital heart defect (CHD), also known as a congenital heart anomaly, congenital cardiovascular malformation, and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital he ...

. The results of this study showed that nirsevimab had a similar safety profile compared to

palivizumab Palivizumab, sold under the brand name Synagis, is a monoclonal antibody produced by recombinant DNA technology used to prevent severe disease caused by respiratory syncytial virus (RSV) infections. It is recommended for infants at high-risk for ...

(Synagis). The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(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). 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. 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. 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. Of the 1,453 preterm infants in the trial, 969 received a single dose of nirsevimab and 484 received placebo. Among infants who were treated with nirsevimab, 25 (2.6%) experienced MA RSV LRTI compared with 46 (9.5%) infants who received placebo. nirsevimab reduced the risk of MA RSV LRTI by approximately 70% relative to placebo. For Trial 04, the primary analysis group within the trial included 1,490 term and

late preterm infant Late preterm infants are infants born at a gestational age between weeks and weeks. They have higher morbidity and mortality rates than term infants (gestational age ≥37 weeks) due to their relative physiologic and metabolic immaturity, even t ...

s (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. Among infants who were treated with nirsevimab, 12 (1.2%) experienced MA RSV LRTI compared with 25 (5.0%) infants who received placebo. Nirsevimab reduced the risk of MA RSV LRTI by approximately 75% relative to placebo. Trial 05, a randomized, double-blind, active (

)-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. The trial enrolled 925 preterm infants and infants with chronic lung disease of prematurity or congenital heart disease. The safety and pharmacokinetic data from Trial 05 provided evidence for the use of nirsevimab to prevent MA RSV LRTI in this population. The FDA granted the application for nirsevimab a

fast track Fast Track, Fast track, or Fasttrack may refer to: Processes and systems * Fast track (FDA), a U.S. Food and Drug Administration expedited review program * Fast track (trade), the authority of the U.S. President to broker trade agreements with lim ...

designation. and granted approval of Beyfortus to AstraZeneca.

Society and culture

Legal status

In 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. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Beyfortus was reviewed under EMA's accelerated assessment program. The applicant for this medicinal product is AstraZeneca AB. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In November 2022, nirsevimab was approved for medical use in the European Union, and the United Kingdom. It was approved in Canada in April 2023, and in the United States in July 2023.

Research

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. 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. As of April 2023, ongoing trials for nirsevimab were: * * *

References

{{Portal bar , Medicine , Viruses Antiviral drugs Drugs developed by AstraZeneca Monoclonal antibodies Sanofi Respiratory syncytial virus