Profile
General Information
Beyfortus (nirsevimab-alip) is a respiratory syncytial virus (RSV) F protein-directed fusion inhibitor.
Beyfortus is specifically indicated for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease (LRTD) in:
Neonates and infants born during or entering their first RSV season
Children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
Dosing/Administration
Beyfortus is supplied as an intramuscular injection.
Recommended dosage:
- Neonates and infants born during or entering their first RSV season: 50 mg if less than 5 kg in body weight. 100 mg if greater than or equal to 5 kg in body weight.
- Children who remain vulnerable through their second RSV season: • 200 mg (2 x 100 mg injections)
Mechanism of Action
Nirsevimab-alip is a recombinant human IgG1κ monoclonal antibody that provides passive immunity by targeting the prefusion conformation of the RSV F protein. Nirsevimab-alip is long-acting due to a triple amino acid substitution (YTE) in the Fc region which increases binding to the neonatal Fc receptor and thereby extends serum half-life. Nirsevimab-alip binds to a conserved epitope in antigenic site on the prefusion protein with dissociation constants KD = 0.12 nM and KD = 1.22 nM for RSV subtype A and B strains, respectively; it neutralizes RSV by inhibiting conformation changes in the F protein necessary for fusion of the viral and cellular membranes and viral entry.
Side Effects
Adverse effects associated with the use of Beyfortus may include, but are not limited to, the following:
- rash
- injection site reactions
Hypersensitivity Including Anaphylaxis: Serious hypersensitivity reactions, including anaphylaxis, have been observed with other human IgG1 monoclonal antibodies. Initiate appropriate medications and/or supportive therapy.
Clinical Trial Results
FDA approval was based on the following trials:
MEDLEY (Trial 05) was a Phase II/III, randomized, double-blind, Synagis-controlled trial with the primary objective of assessing safety and tolerability for Beyfortus in preterm infants of less than 35 weeks gestational age and infants with congenital heart disease (CHD) and/or chronic lung disease of prematurity (CLD) eligible to receive Synagis. Between July 2019 and May 2021 a total of 925 infants entering their first RSV season were randomized to receive Beyfortus or Synagis.
The primary endpoint of the MELODY trial was met, reducing the incidence of medically attended LRTI, such as bronchiolitis or pneumonia, caused by RSV by 74.9% compared to placebo. Observed events were 1.2% in treatment arm vs 5% in placebo arm. The efficacy of Beyfortus against the secondary endpoint of hospitalisation was 60.2%. Observed events were 0.6% in treatment arm vs 1.6% in placebo arm.
The Phase IIb (Trial 03) study was a randomised, placebo-controlled trial designed to measure the efficacy of Beyfortus against medically attended (MA) Lower Respiratory Tract Infection (LRTI) through 150 days post-dose. Healthy preterm infants of 29 to less than 35 weeks’ gestational age were randomised (2:1) to receive a single 50mg intramuscular injection of Beyfortus or placebo regardless of weight.
The primary endpoint of the Phase IIb study was met, reducing the incidence of medically attended LRTI caused by RSV by 70.1% compared to placebo. Observed events were 2.6% in treatment arm vs 9.5% in placebo arm. Between November 2016 and December 2017, 1,453 infants were randomised (Beyfortus, n=969; placebo, n=484) at the RSV season start.
In a prespecified secondary endpoint, Beyfortus reduced medically attended RSV LRTI with hospitalization by 78.4% versus placebo. Observed events were 0.8% in treatment arm vs 4.1% in placebo arm.nA post-hoc analysis of the Phase IIb study that applied the recommended 50 mg dose in a subgroup of infants weighing less than 5 kg showed the efficacy of Beyfortus against medically attended RSV LRTI and medically attended RSV LRTI with hospitalization was 86.2% and 86.5%, respectively.