Drug Update · Pediatrics

FDA Approves Nirsevimab for RSV Prevention: 74.5% MA RSV LRTI in MELODY

July 08, 2026

drug

nirsevimab (Beyfortus)

approval_date

2023-07-17

primary_result

74.5% efficacy for medically attended RSV-associated LRTI; 1.2% vs 5.0% through 150 days (95% CI, 49.6 to 87.1; P<0.001) [1]

trial_name

MELODY (Trial 04 primary cohort)

approved_dose

First RSV season: 50 mg if <5 kg; 100 mg if ≥5 kg. Second RSV season: 200 mg (2 × 100 mg) [12][3]

Clinical Perspective

Pediatricians, neonatologists, family physicians, and pharmacists caring for infants should note that BEYFORTUS is now an FDA-approved single-dose intramuscular prophylaxis to prevent RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and for certain children up to 24 months in a second season ^[4]^[2]. The randomized-trial data support substantial reduction in medically attended RSV LRTI through 150 days after dosing, which may influence decisions around seasonal prophylaxis in eligible infants ^[1]^[3]^[4]. Clinicians should verify weight at dosing, follow the weight-based dose schedule in the prescribing information, and monitor for hypersensitivity reactions after administration ^[2]^[4].

Dr. Sneha Rao · Pediatrics

The FDA approved nirsevimab (Beyfortus) on July 17, 2023 for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season and in children up to 24 months who remain vulnerable through a second RSV season ^[4]^[3]. Approval was supported by randomized trials including the MELODY trial, in which nirsevimab reduced medically attended RSV-associated lower respiratory tract infection by 74.5% (1.2% vs 5.0%) through 150 days after a single dose (95% CI, 49.6 to 87.1; P<0.001) ^[1]^[3].

Clinical Context

Nirsevimab is a respiratory syncytial virus F protein-directed monoclonal antibody developed to provide passive immunoprophylaxis against RSV in infants and young children ^[4]. It is manufactured and marketed as BEYFORTUS by Sanofi Vaccines US Inc. and was evaluated across multiple Phase 2 and Phase 3 trials including Trials 03, 04, and 05 as summarized in regulatory materials and labeling ^[4]^[3]^[2]. The regulatory dossier and labeling describe intramuscular administration with weight-based dosing for the first RSV season and a two-injection 200 mg regimen for select children in a second season ^[4]^[2]. Clinicians should consult current prescribing information for full dosing guidance. The approval references efficacy for prevention of medically attended RSV lower respiratory tract infection measured through 150 days after dosing in randomized, placebo-controlled trials ^[1]^[3]^[4].

Key Findings

The MELODY trial (Trial 04 primary cohort) showed nirsevimab achieved medically attended RSV-associated lower respiratory tract infection in 1.2% of recipients versus 5.0% with placebo through 150 days after injection, corresponding to an efficacy of 74.5% (95% CI, 49.6 to 87.1; P<0.001) ^[1].
In Trial 03 (preterm infants ≥29 to <35 weeks), BEYFORTUS reduced MA RSV LRTI from 9.5% with placebo to 2.6% with nirsevimab, with an efficacy of 70.1% (95% CI, 52.3 to 81.2; P=<0.001) ^[4]^[1].
Hospitalization for RSV-associated LRTI was a prespecified secondary endpoint; in MELODY hospitalization occurred in 0.6% with nirsevimab versus 1.6% with placebo (efficacy 62.1%; 95% CI, -8.6 to 86.8; P = 0.07) in the larger trial report ^[1].
The FDA-approved dosing for the first RSV season is weight-based: 50 mg IM for neonates and infants weighing less than 5 kg and 100 mg IM for those weighing greater than or equal to 5 kg; for children up to 24 months who remain vulnerable in a second RSV season the recommended dose is 200 mg administered as two 100 mg IM injections (2 × 100 mg) ^[4]^[2]. Clinicians should consult current prescribing information for complete dosing guidance.

Safety & Tolerability

Serious hypersensitivity reactions including anaphylaxis, and signs such as urticaria, dyspnea, cyanosis, and hypotonia have been reported with BEYFORTUS administration ^[2].
Most common adverse reactions listed in the prescribing information were rash (0.9%) and injection site reactions (0.3%) ^[2].
In clinical trials, antidrug antibodies after baseline were detected in 58 of 951 (6.1%) in the nirsevimab group and in 5 of 473 (1.1%) in the placebo group among infants with data to day 361 ^[1].
Serious adverse events were reported in 67 of 987 infants (6.8%) who received nirsevimab and in 36 of 491 infants (7.3%) who received placebo in the trial safety datasets ^[1].

Study Design

The FDA approval was supported by multiple trials summarized in the prescribing information and the NEJM MELODY publication. Trial 04 (MELODY) was a Phase 3, randomized, double-blind, placebo-controlled multicenter trial in infants born at greater than or equal to 35 weeks gestational age; subjects were randomized 2:1 to receive a single IM dose of nirsevimab (50 mg if <5 kg or 100 mg if ≥5 kg) or placebo, with the primary endpoint of medically attended RSV-associated lower respiratory tract infection through 150 days after dosing ^[1]^[4]. Clinicians should consult current prescribing information for full dosing guidance. Trial 03 enrolled infants ≥29 to <35 weeks GA and was randomized 2:1 to nirsevimab or placebo; efficacy and safety populations and pooled safety analyses are described in the labeling and NEJM report ^[4]^[1].

FAQ

What is nirsevimab (Beyfortus) approved for?

BEYFORTUS (nirsevimab-alip) is approved to prevent Respiratory Syncytial Virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season, per the FDA-approved labeling and press announcement.

How does nirsevimab work?

Nirsevimab is a monoclonal antibody directed against the RSV fusion (F) protein; it is designed to neutralize the virus and provide passive immunity when administered as a single intramuscular injection prior to or during RSV season, according to the FDA labeling and clinical study descriptions.

What is the recommended dose of nirsevimab for infants?

For neonates and infants in their first RSV season, the recommended dosage is weight-based: 50 mg by intramuscular injection for those weighing less than 5 kg and 100 mg by intramuscular injection for those weighing greater than or equal to 5 kg. For children up to 24 months who remain vulnerable in a second RSV season the recommended dose is 200 mg administered as two 100 mg intramuscular injections (2 × 100 mg). BEYFORTUS must be administered by a healthcare provider; consult the full prescribing information for administration and special dosing guidance. Clinicians should consult current prescribing information for complete dosing guidance.

What are the side effects of nirsevimab?

The prescribing information lists hypersensitivity reactions including anaphylaxis and associated signs such as urticaria, dyspnea, cyanosis, and hypotonia. The most common adverse reactions were rash (0.9%) and injection site reactions (0.3%). Trial safety data reported antidrug antibodies in 58 of 951 (6.1%) nirsevimab recipients versus 5 of 473 (1.1%) placebo and serious adverse events in 67 of 987 (6.8%) nirsevimab recipients versus 36 of 491 (7.3%) placebo in pooled safety datasets. Clinicians should monitor for hypersensitivity after administration and consult the full labeling for complete safety and contraindication information.

FDA Approves Nirsevimab for RSV Prevention: 74.5% MA RSV LRTI in MELODY

FDA Approves Nirsevimab for RSV Prevention: 74.5% MA RSV LRTI in MELODY

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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