Beyfortus™—
Now ACIP Recommended!
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Efficacy & Safety

Trial design1

The efficacy of Beyfortus was evaluated in 3 randomized, double-blind, multicenter trials––Trial 04 (Phase 3 MELODY), Trial 03 (Phase 2b), and Trial 05 (Phase 2/3 MEDLEY)––for the prevention of RSV lower respiratory tract infection. A total of 3,224 pediatric subjects received the recommended dose of Beyfortus in Phase 2 and Phase 3 clinical trials.

  • Trial 04 included 1,490 late preterm and term infants (≥35 wGA) entering their first RSV season
  • Trial 03 was conducted in 1,453 preterm infants (≥29 to <35 wGA) entering their first RSV season
  • Trial 05 included 925 infants:
    • Entering first RSV season: Infants born at <35 weeks GA and infants born with CLD of prematurity or hemodynamically significant CHD
    • Entering second RSV season: Infants with CLD or CHD
TRIAL 04*†
N=1,490		TRIAL 03‡
N=1,453
BEYFORTUSn=994n=969
PLACEBOn=496n=484
DOSINGA single IM dose of Beyfortus (50 mg if <5 kg weight or 100 mg if ≥5 kg weight at the time of dosing), or placebo50 mg of Beyfortus or placebo were administered regardless of body weight at time of dosing
TRIAL 04*†
N=1,490
BEYFORTUSn=994
PLACEBOn=496
DOSING

A single IM dose of Beyfortus (50 mg if <5 kg weight or 100 mg if ≥5 kg weight at the time of dosing), or placebo

TRIAL 03‡
N=1,453
BEYFORTUSn=969
PLACEBOn=484
DOSING

50 mg of Beyfortus or placebo were administered regardless of body weight at time of dosing

Primary endpoint

Incidence of medically attended RSV lower respiratory tract infections (MA RSV-LRTIs) caused by RT-PCR–confirmed RSV, characterized predominantly as bronchiolitis or pneumonia through 150 days after dosing§

Secondary endpoint

Incidence of RSV lower respiratory tract infections (RSV-LRTIs) with hospitalization. RSV hospitalization was defined as hospitalization for LRTI with a positive RSV test

TRIAL 05
N=925		RSV SEASON ONERSV SEASON TWO
BEYFORTUSn=616n=220
PALIVIZUMABn=304n=42
POPULATIONInfants born at <35 weeks GA and infants born with CLD or CHD entering their first RSV seasonInfants with CLD or CHD only entering their second RSV season
TRIAL 05
N=925
RSV SEASON ONE
BEYFORTUSn=616
PALIVIZUMABn=304
POPULATION

Infants born at <35 weeks GA and infants born with CLD or CHD entering their first RSV season

RSV SEASON TWO
BEYFORTUSn=220
PALIVIZUMABn=42
POPULATION

Infants with CLD or CHD only entering their second RSV season

The safety and pharmacokinetics (PK) of Beyfortus were evaluated in a Phase 2/3 randomized, double-blind, palivizumab-controlled multicenter Trial 05 in pediatric subjects born <35 wGA and infants with CLD of prematurity or hemodynamically significant CHD.

This trial was not powered for efficacy, but efficacy was assessed as secondary endpoint.||

Signs of LRTI involvement included rhonchi, rales, crackles, or wheezing; and at least one sign of worsening clinical severity, including at least one of the following: increased respiratory rate, hypoxemia, acute hypoxic or ventilatory failure, new onset apnea, nasal flaring, retractions, grunting, or dehydration due to respiratory distress.

CHD, congenital heart disease; CLD, chronic lung disease; RT-PCR, reverse transcription polymerase chain reaction; wGA, gestational age (weeks).

*The primary efficacy analysis for Trial 04 is based on subjects from the Primary Cohort.

†Trial 04 safety analysis included both Primary and Safety Cohorts.

ǂAll subjects in Trial 03 were included in the efficacy analysis. All subjects in Trial 03 received 50 mg of Beyfortus IM injections regardless of body weight. The recommended Beyfortus dose in neonates and infants born during or entering their first RSV season is a single IM 50 mg and 100 mg dose for those who weigh <5 kg and ≥5 kg, respectively.

§Medically attended (MA) includes all healthcare provider visits such as physician’s office, urgent care, emergency room, and hospitalizations.

||The efficacy of Beyfortus in preterm infants (GA less than 35 weeks) during their first RSV season and in pediatric subjects up to 24 months of age with CLD or CHD during their first and second RSV season was established by extrapolation of efficacy of Beyfortus from Trial 03 and Trial 04 to the population enrolled in Trial 05 based on similar nirsevimab-alip exposures among subjects enrolled in Trial 04 and Trial 05.

Efficacy

Incidence of MA RSV-LRTI
through 150 days post dose (primary endpoint)

INFANTS BORN AT ≥35 wGA

Trial 04

74.9

%

RRR

(95% CI: 50.6, 87.3; P≤0.001)1*†

Beyfortus: 1.2% (12)

Placebo: 5.0% (25)

INFANTS BORN AT ≥29 TO <35 wGA

Trial 03

70.1

%

RRR

(95% CI: 52.3, 81.2; P<0.001)1‡§

Beyfortus: 2.6% (25)

Placebo: 9.5% (46)

Cl, confidence interval; MA RSV-LRTI, medically attended respiratory syncytial virus lower respiratory tract infection; RRR, relative risk reduction; wGA, gestational age (weeks).

*The primary efficacy analysis for Trial 04 is based on subjects from the Primary Cohort.

†Efficacy for MA RSV-LRTI based on relative risk reduction against placebo adjusted for age at randomization.

‡Efficacy for MA RSV-LRTI based on relative risk reduction against placebo adjusted for age at randomization and hemisphere.

§In a post hoc analysis of all randomized infants in Trial 03 weighing <5 kg at baseline, and who received the recommended dose of Beyfortus, efficacy for MA RSV-LRTI based on relative risk reduction against placebo was 86.2% (95% CI: 68.0, 94.0); efficacy for RSV-LRTI with hospitalization based on relative risk reduction against placebo was 86.5% (95% CI: 53.5, 96.1).

Trial 03 and Trial 04 clinical results

Incidence of MA RSV-LRTI in Infants Born at ≥29 to <35 wGA Through 150 Days Post Dose (Trial 03)1

NINCIDENCE
% (n)		EFFICACY* (95% CI)
Beyfortus9692.6% (25)70.1% (52.3, 81.2)†‡  
Placebo4849.5% (46)
Incidence of MA RSV-LRTI in Infants Born at ≥29 to <35 wGA Through 150 Days Post Dose (Trial 03)1
BeyfortusN
969
INCIDENCE % (n)
2.6% (25)
PlaceboN
484
INCIDENCE % (n)
9.5% (46)
EFFICACY* (95% CI)
70.1% (52.3, 81.2)†‡

*Efficacy for MA RSV-LRTI based on relative risk reduction against placebo adjusted for age at randomization and hemisphere.

†p-value =<0.001.

‡In a post hoc analysis of all randomized infants in Trial 03 weighing <5 kg at baseline, and who received the recommended dose of Beyfortus, efficacy for MA RSV-LRTI based on relative risk reduction against placebo was 86.2% (95% CI: 68.0, 94.0); efficacy for RSV-LRTI with hospitalization based on relative risk reduction against placebo was 86.5% (95% CI: 53.5, 96.1).

Incidence of MA RSV-LRTI in Infants Born at ≥35 wGA Through 150 Days Post Dose (Trial 04)1*

NINCIDENCE
% (n)		EFFICACY† (95% CI)
Beyfortus9941.2% (12)74.9% (50.6, 87.3)‡  
Placebo4965.0% (25)
Incidence of MA RSV-LRTI in Infants Born at ≥35 wGA Through 150 Days Post Dose (Trial 04)1*
BeyfortusN
994
INCIDENCE % (n)
1.2% (12)
PlaceboN
496
INCIDENCE % (n)
5.0% (25)
EFFICACY† (95% CI)
74.9% (50.6, 87.3)‡

*The primary efficacy analysis for Trial 04 is based on infants from the Primary Cohort.

†Efficacy for MA RSV-LRTI based on relative risk reduction against placebo adjusted for age at randomization.

‡p-value =<0.001.

Safety1

The safety profile of Beyfortus in infants in their first RSV season was comparable to placebo1*†

*Based on trials: Trial 03 evaluated the efficacy and safety of a single 50 mg dose of Beyfortus in 1,453 very and moderately preterm (≥29 to <35 wGA) infants (age 12 months or under) entering their first RSV season (N=969) vs placebo (N=484). Trial 04 evaluated the efficacy and safety of a single 50 mg or 100 mg administration of Beyfortus for the prevention of LRTls in 1,490 term and late preterm (≥35 wGA) infants (age 12 months or under) entering their first RSV season (N=994) vs placebo (N=496). Trial 05 evaluated the safety of Beyfortus compared to palivizumab, randomizing a total of 925 infants at higher risk for severe RSV disease, including infants with CLD of prematurity or hemodynamically significant CHD, and preterm infants (<35 wGA) entering their first RSV season.

†Studies included healthy preterm infants, healthy full term infants, and infants with underlying conditions. Higher risk infants included 196 extremely preterm infants (<29 wGA) and 306 infants with CLD, prematurity, or hemodynamically significant CHD.

Safety was comparable to placebo––neonates and infants entering their first RSV season1

Infants who received the recommended dose in Trial 03 and infants in Trial 04 were pooled to evaluate the safety of Beyfortus (N=2,570) compared to placebo (N=1,284).

    This included:
  • 1,998 full term and late preterm infants (≥35 wGA)
  • 572 very and moderately preterm infants (≥29 to <35 wGA)
    Safety results found that:
  • Majority of adverse reactions were mild to moderate in severity

Adverse Reactions Reported at an Incidence Higher Than Placebo in the Safety Population Trial 03 and Trial 041*

ADVERSE
REACTION		BEYFORTUS
N=2,570
%  		PLACEBO
N=1,284
%  
RASH*†
(occurring within 14 days post dose)		0.90.6
INJECTION SITE REACTION‡
(occurring within 7 days post dose)		0.30.0

*The Safety Population includes all infants who received the recommended dose of Beyfortus in Trials 03 and 04: Primary and Safety cohorts from Trial 04; infants who weighed less than 5 kg and who received the recommended dose of Beyfortus (single 50 mg IM dose) in Trial 03.

†Rash was defined by the following grouped preferred terms: rash, rash maculopapular, rash macular, rash papular.1

‡Injection site reaction was defined by the following group preferred terms: injection site reaction, injection site pain, injection site induration, injection site edema, injection site swelling.1

Safety studies in a broad range of infants, including those at higher risk of severe disease1

RSV season one

  • The safety of Beyfortus was evaluated in Trial 05, a randomized, double-blind, palivizumab-controlled multicenter trial in subjects at high risk for severe RSV disease
  • Adverse reactions reported among Trial 05 subjects who received Beyfortus in their first RSV season were similar to those reported in subjects who received Beyfortus in Trials 03 and 04

RSV season two (Subjects with CLD of prematurity and hemodynamically significant CHD)

  • Subjects with CLD of prematurity or hemodynamically significant CHD could continue in Trial 05 and receive Beyfortus or palivizumab prior to their second RSV season. All subjects who received Beyfortus in the first RSV season also received Beyfortus in the second RSV season (N=180)
  • The safety profile of Beyfortus in these subjects during their second RSV season was consistent with the safety profile of Beyfortus observed during their first RSV season

CHD, congenital heart disease; CLD, chronic lung disease.

IMPORTANT SAFETY INFORMATION
Contraindication

Beyfortus is contraindicated in infants and children with a history of serious hypersensitivity reactions, including anaphylaxis, to nirsevimab-alip or to any of the excipients.

Warnings and Precautions

  • Hypersensitivity Including Anaphylaxis: Serious hypersensitivity reactions, including anaphylaxis, have been observed with other human IgG1 monoclonal antibodies. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, initiate appropriate medications and/or supportive therapy.

  • Use in Individuals with Clinically Significant Bleeding Disorders: As with other IM injections, Beyfortus should be given with caution to infants and children with thrombocytopenia, any coagulation disorder or to individuals on anticoagulation therapy.

Most common adverse reactions with Beyfortus were rash (0.9%) and injection site reactions (0.3%).

Please see full Prescribing Information.

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INDICATION

Beyfortus is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease 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.
IMPORTANT SAFETY INFORMATION
Contraindication

Beyfortus is contraindicated in infants and children with a history of serious hypersensitivity reactions, including anaphylaxis, to nirsevimab-alip or to any of the excipients.

Warnings and Precautions
INDICATION

Beyfortus is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in:

  • Neonates and infants born during or entering their first RSV season.
INDICATION

Beyfortus is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in:

Reference: 1. Beyfortus (nirsevimab-alip). Prescribing Information. Sanofi.