Real-World Evidence
Tested, Trusted, and Demonstrated

Beyfortus Pivotal Trial Data

In 2 randomized, placebo-controlled pivotal trials, Beyfortus demonstrated efficacy against MA RSV-LRTI and RSV hospitalization^1-4*

In Trial 04, Beyfortus exhibited a reduction in MA RSV hospitalization
compared to placebo: healthy preterm infants (≥35 wGA)

In Trial 03, Beyfortus exhibited a reduction in MA RSV-LRTI and RSV hospitalization compared to placebo: healthy preterm infants (≥29 to <35 wGA)^2,5

The most common adverse reactions in Trial 04 and Trial 03 were rash (0.9%) and injection site reactions (0.3%).^2**

Trial 04 and Trial 03 were pooled to evaluate the safety of Beyfortus (N=2,570) compared to placebo (N=1,284).²
• Adverse reactions were reported in 1.2% of infants who received Beyfortus; most (97%) of adverse reactions were mild to moderate in severity

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.²

CI, confidence interval; IM, intramuscular; MA RSV-LRTI, medically attended respiratory syncytial virus lower respiratory tract infection; RWE, real-world evidence; RRR, relative risk reduction; wGA weeks gestational age.

*Results of Trials 04 and 03 for infants entering their first RSV season.^2
†Primary Cohort: 1,490 healthy term and late preterm infants (≥35 wGA) in Trial 04.^2
‡During Trial 04, the COVID-19 pandemic interrupted trial enrollment. The efficacy analysis is based on the Primary Cohort, which included those participants enrolled prior to the pause due to COVID-19. Trial 04 continued monitoring the Primary Cohort and included an additional 1,522 subjects enrolled after the pause to comprise the full study cohort. The full study cohort included 3,012 infants randomized to receive Beyfortus or placebo in the post hoc analysis.^4
§Efficacy for MA RSV-LRTI based on RRR against placebo adjusted for age at randomization.^2
||1,453 preterm infants (≥29 to <35 wGA) in Trial 03.^2
¶Efficacy for MA RSV-LRTI based on RRR against placebo adjusted for age at randomization and hemisphere.^2
#860 infants from the full study cohort of 1,453 healthy preterm infants in Trial 03 were analyzed in a post hoc analysis. For infants in their first RSV season, the recommended dose is 50 mg for infants <5 kg or 100 mg for infants ≥5 kg via IM injection.^1,2
**The Safety Population includes all infants who received the recommended dose of Beyfortus in Trials 04 and 03: Primary and Safety cohorts from Trial 04; infants who weighed <5 kg and who received the recommended dose of Beyfortus (single 50 mg IM dose) in Trial 03.²

Discover real-world data for Beyfortus

Beyfortus effectiveness against medically attended respiratory syncytial virus (RSV) events in infants (BEAR) is an observational, retrospective cohort study that assessed the effectiveness of Beyfortus at Kaiser Permanente Northern California (KPNC) during the 2023-2024 RSV season.⁶

Download the summary >

Study Design

Beyfortus was associated with a reduction in MA RSV-LRTI and RSV hospitalization in healthy term US infants (aged <8 months and born at ≥37 wGA).⁶

This study included 31,900 healthy term infants aged <8 months (≥37 wGA) born on or after April 1, 2023, without a pre-defined high-risk condition during the 2023-2024 RSV season. Beyfortus was routinely administered beginning October 19, 2023, at KPNC.^6*

• 15,647 infants received Beyfortus compared to 16,253 infants who were non-immunized

Co-primary endpoints⁶:

• First episode of PCR-confirmed RSV-LRTI during the RSV season^†
• Healthcare utilization as measured by the total number of medical encounters related to each RSV-LRTI episode^‡

Post hoc analysis⁶:

• RSV hospitalization^§

BEAR Study Results⁶

Co-primary endpoints

Total RSV-LRTI medical encounters related to RSV-LRTI episodes⁶:

Post hoc analysis

The findings in this analysis are subject to limitations⁶:

• Investigators were unable to assess how soon after receipt Beyfortus protection occurs because few RSV-LRTI cases occurred within 7 days
• Although KPNC performs a large amount of PCR testing, investigators did not quantify what proportion of infants with respiratory symptoms were tested, so testing biases among RSV-positive infants were possible
• As an observational study, unmeasured confounders that increase one’s risk of RSV (eg, lower socioeconomic status, having siblings, and/or daycare attendance) could affect results
• The analysis population of healthy term infants may not be generalizable to infants at higher risk of RSV-LRTI
• While KPNC has a large and diverse population, the study population may not be representative of other health systems’ populations

 CI, confidence interval; ED, emergency department; MA RSV-LRTI, medically attended respiratory syncytial virus lower respiratory tract infection; PCR, polymerase chain reaction; wGA, weeks gestational age. 

*Eligible infants born on or after this date were offered the treatment before discharge, during urgent care visits, or at outpatient well-child appointments. Eligible infants born prior to this date were contacted by KPNC as part of routine care for catch-up dosing in outpatient clinics.^6
†An episode is defined as having at least 1 LRTI-associated encounter in any setting in the 7 days before, and up to 10 days after, a positive RSV PCR test.^6
‡Each medical encounter was categorized as outpatient, emergency department, inpatient, or intensive care unit.^6
§Episodes that included at least 1 hospitalization were considered a hospitalized RSV-LRTI.⁶

The analysis was a population-based, prospective, active surveillance study that assessed the effectiveness of Beyfortus within the New Vaccine Surveillance Network (NVSN) during the 2023-2024 RSV season.⁷

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Study Design

Beyfortus was associated with preventing MA RSV ARI and RSV hospitalization in US infants (aged <8 months)^7*

This study included infants <8 months as of October 1, 2023, or born after October 1, 2023, who had medically attended acute respiratory illness (ARI) between October 2023 and March 2024, who had verified Beyfortus status and medical records to assess underlying medical conditions, and were within the NVSN, which includes 7 sites.^†

• N=1,616 medically attended ARI (case patients receiving positive RSV test result n=765, control patients receiving negative RSV test result n=851)^‡
• Infants were considered Beyfortus recipients if they received Beyfortus ≥7 days before symptom onset^§

CDC real-world analysis results⁷

Estimated effectiveness against MA RSV ARI

Estimated effectiveness against RSV hospitalization⁷

Among RSV isolates, there were no variants in the Beyfortus binding site on the F protein that would alter susceptibility of RSV to Beyfortus⁷

The findings in this report are subject to limitations⁷:

• The efficacy and safety follow-up had a short duration of approximately 3 months for the majority of infants
• The trial design did not include blinded group assignments; parents and legally acceptable representatives knew which arm their infant was enrolled in. Bias mitigation steps were taken
• Infants without LRTI may have been hospitalized for reasons related to RSV, such as dehydration (among 158 infants hospitalized for any-cause LRTI, 16 did not undergo RSV testing)

CDC, Centers for Disease Control and Prevention; IQR, interquartile range; MA RSV ARI, medically attended respiratory syncytial virus acute respiratory illness.

*Medically attended RSV was defined as any medically attended RSV-associated ARI and hospitalization was defined as RSV-associated hospitalization for ARI.^7
†ARI is defined as one or more of the following signs or symptoms present for <14 days before enrollment encounter: apnea, cough, earache, fever, myalgia, nasal congestion, runny nose, sore throat, vomiting after coughing, shortness of breath (rapid or shallow breathing), wheezing, or apparent life-threatening event or brief resolved unexplained event.^7
‡Ten out of 765 case patients who received Beyfortus were RSV positive compared with 126 out of 851 control patients who were negative for RSV.^7
§Receipt of Beyfortus was ascertained through parent/guardian interviews, medical record abstraction, outpatient records, and state immunization information systems.^7
‖Based on the median time from receipt of Beyfortus to symptom onset of 44 days (IQR=21-73 days).^7
¶Based on the median time from receipt of Beyfortus to symptom onset of 41 days (IQR=18-68 days).^7
#Of 875 hospitalized patients, 531 (61%) were case patients with a positive RSV result and 344 (39%) were control patients with a negative RSV result. Six out of 531 case patients who received Beyfortus were RSV positive compared with 67 out of 344 control patients who were negative for RSV.⁷

HARMONIE is a Phase 3b, open-label, 2-arm, randomized trial to determine the efficacy and safety of Beyfortus in preventing RSV hospitalization in infants entering their first RSV season in Europe (2022-2023 RSV season).⁵

Download the summary >

Study Design

Beyfortus was associated with a reduction in RSV hospitalization in healthy term and preterm infants (aged ≤12 months and born at ≥29 wGA)^8*

The phase 3b HARMONIE study was a pragmatic, open-label, randomized, parallel, 2-arm trial that studied Beyfortus vs no intervention in healthy term and preterm infants ≤12 months (≥29 wGA) entering their first RSV season in France, Germany, or the United Kingdom. The RSV season ended on February 28, 2023, in each country.⁸

The findings in this report are subject to limitations⁸:

• The efficacy and safety follow-up had a short duration of approximately 3 months for the majority of infants
• The trial design did not include blinded group assignments; parents and legally acceptable representatives knew which arm their infant was enrolled in. Bias mitigation steps were taken
• Infants without LRTI may have been hospitalized for reasons related to RSV, such as dehydration (among 158 infants hospitalized for any-cause LRTI, 16 did not undergo RSV testing)

HARMONIE interim safety results^8-10

Adverse reactions in safety analysis population: healthy infants aged ≤12 months⁸

Most adverse events in the two trial groups were grade 1 or 2 in severity

*RSV hospitalization was defined as hospitalization for RSV-associated LRTI with hospital admission and an RSV-positive test result.^8
†Infants could be born before or during the RSV season, which began on September 11, 2022 (week 37) in France; on October 9, 2022 (week 41) in Germany; and on September 4, 2022 (week 36) in the United Kingdom. The RSV season ended on February 28, 2023, in each country.^8
‡Overall incidence of hospitalization for RSV-LRTI was defined as admission to the hospital on the basis of the treating physician’s decision and confirmation of RSV by means of a positive result of a test performed in accordance with routine practice, during the RSV season in France, Germany, and the United Kingdom.^8
§8,058 infants were randomized 1:1 to receive either a single IM injection of Beyfortus or the standard care (no intervention) (Beyfortus [n=4,037] or no intervention [n=4,021]) before or during the 2022-2023 RSV season. The characteristics of infants at randomization were similar in the 2 groups and 85.2% of infants were ≥37 wGA at birth. The trial was closed to recruitment on February 28, 2023, which was used as the data-cutoff date for the initial event-driven primary analysis. The final analysis will be performed when all the enrolled infants complete the scheduled 12-month safety follow-up.<sup>8

||</sup>The 2-sided 95% Cl for the efficacy is calculated by an exact method assuming a binomial distribution of the number of RSV-LRTI hospitalizations in the Beyfortus group conditional on the total number in both groups (described by Breslow and Day) accounting for the follow-up time post-dosing/randomization.^9
¶Four infants had at least one adverse event of special interest, all of which were assessed to be grade 1 or 2 in severity.^8
#One infant had a grade 3 serious adverse event 23 days after the receipt of Beyfortus that was considered to be related to the trial treatment because the relationship to Beyfortus could not be excluded; however, the occurrence of this event was within the expected background rate for a trial of this size. Two infants discontinued the trial because of safety events. All the medically attended adverse events occurred in a similar percentage of infants in each trial group. No deaths were reported.^8,10
**Medically attended adverse events are listed according to system organ classes and preferred terms in the Medical Dictionary for Regulatory Activities, version 25.0, and include those that occurred in at least 1% of infants in at least 1 of the 2 trial groups. Medically attended adverse events were events that prompted the infant’s parents or legally acceptable representatives to seek unplanned in-person medical advice in any clinical setting.^8,9