Infant RSV Disease Prevention: Helping Patients Understand the Options to Help Protect Their Baby

Attributed to Dr. Ruth Ann Crystal
This article was sponsored by Sanofi.

For many in obstetrics, counseling patients on Respiratory Syncytial Virus (RSV) is new territory. Until last year we seldom discussed it with expectant parents, as those conversations were primarily handled by pediatricians. In 2023, we saw a shift in infant RSV disease prevention options, transitioning from one preventative medication made specifically for high-risk infants to having two immunizations approved by the United States Food and Drug Administration (FDA). These two options, one a maternal vaccine given in the third trimester of pregnancy and one a monoclonal antibody given directly to infants after birth, are recommended by the American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP).

Two out of three babies are infected with RSV by age one.¹ RSV is a seasonal disease that usually occurs from the fall through the spring, though timing can vary by local area.² Although most RSV presents with mild cold-like symptoms, RSV is unpredictable and can progress from cold-like symptoms to hospitalization fairly quickly, even in term babies, as infants have very small airways that can make them more susceptible to bronchiolitis.^3,4 Infants are 16x more likely to be hospitalized with an RSV lung infection than with the flu.⁵

Helping to prevent RSV in babies whose immune systems have not fully matured is crucial for reducing severe RSV lower respiratory tract disease (LRTD). With these two immunizations available, we can now help turn the page on RSV, helping to potentially reduce the burden typically placed on babies.

Navigating the different options as we counsel patients on RSV disease prevention options

ACOG guidelines state that clinicians who work with pregnant patients should counsel on both FDA-approved options to help protect babies against RSV. Here are some things I think about when I am counseling on RSV prevention.

• Framing the Conversation: I like to emphasize the safety and efficacy of both the vaccine given to pregnant patients as well as the monoclonal antibody option given directly to babies, highlighting that both methods are designed to help protect their baby against RSV LRTD.
• Timing the Conversation: The maternal vaccine should be given between 32-36 weeks of pregnancy for babies expected to be born during the RSV season. As expectant parents are preparing for their baby’s arrival during their third trimester, it is an optimal time to discuss RSV disease and both immunization options to help protect their little one.
• Educating on the available options: Maternal vaccines operate by stimulating the pregnant parent’s immune system to generate antibodies, which are then transferred to the baby via the placenta. At least 14 days are needed after maternal vaccination for enough antibodies to be made to help protect the baby after birth. In some cases, babies that are born less than 14 days after maternal vaccination may also receive the monoclonal antibody after birth. Regardless of maternal vaccination status, infants born at less than 34 weeks should receive the monoclonal antibody.
  The RSV monoclonal antibody is a type of infant immunization that delivers ready-made antibodies, providing fast-acting passive immunization directly to the infant without relying on a maturing immune system to mount a response.* It is given to the baby after birth and should protect against RSV disease through 5 months based on clinical data.
• Support Parents Where They Are At: We have all experienced the COVID-19 pandemic and the onslaught of vaccine misinformation and misperceptions – and we have learned a lot from it, including how to approach immunization conversations and customize them for our different patients. Offering expectant parents clear, right-sized information on ways to help protect their babies against RSV LRTD can help lead them to the decision of which option is best for them.

Taking a closer look at data on Beyfortus^® (nirsevimab-alip 50 mg and 100 mg injection), the monoclonal antibody given to baby after birth

Beyfortus is a monoclonal antibody immunization indicated for the prevention of RSV LRTD in neonates and infants born during or entering their first RSV season and children up to 24 months who remain vulnerable to severe RSV disease through their second RSV season.⁶ 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. If a baby is born outside of the season, depending on their local area, they can get Beyfortus at a regular checkup, just before RSV season, when other routine childhood vaccines are given. Beyfortus is the first and only monoclonal antibody product designed to protect a broad infant population through their first RSV season. Beyfortus is indicated for full term and preterm infants, those born healthy or with underlying conditions, who are born during or entering the RSV season.**

Initially after FDA approval, there was insufficient supply of Beyfortus to meet the demand for the 2023-2024 season. The Centers for Disease Control and Protection (CDC) therefore issued an official Health Advisory notice to prioritize high-risk infants and younger infants to receive Beyfortus. By January 2024, additional supply became available, which allowed a return to the original CDC recommendations of administering to all eligible babies going into their first RSV season, no matter if they are premature, born at term or immunocompromised.

The manufacturers expanded the Beyfortus manufacturing network to allow for a significant increase in supply for the 2024/2025 season to cover the entire US demand. They are also producing Beyfortus well in advance of the RSV season, with the vast majority of doses available by October.

Beyfortus is supported both by clinical trials and now by real-world evidence

Beyfortus was studied in two randomized, placebo-controlled studies with the same primary endpoint: incidence of medically attended (MA) RSV Lower Respiratory Tract Infection (LRTI) (including inpatient and outpatient) vs placebo through 150 days post 1 dose. Medically attended includes all healthcare provider visits such as physician’s office, urgent care, emergency room, and hospitalizations.

Beyfortus significantly reduced the risk of MA RSV-LRTI in term and late preterm healthy infants***⁶:

• In Trial 04, Beyfortus demonstrated a relative risk reduction of 74.9% (95% CI: 50.6, 87.3; P<0.001). N=1,490 infants ≥35 weeks gestational age (wGA) (placebo: 5.0% [25/496], Beyfortus: 1.2% [12/994]). Beyfortus dose: 50 mg for <5 kg; 100 mg for ≥5 kg
• In Trial 03, Beyfortus demonstrated a relative risk reduction of 70.1% (95% CI: 52.3, 81.2; P<0.001). N=1,453 infants ≥29 to <35 wGA (placebo: 9.5% [46/484], Beyfortus: 2.6% [25/969]). Beyfortus dose: 50 mg regardless of weight

In both studies, the secondary endpoint was the incidence of RSV-LRTI with hospitalization in term and preterm healthy infants through 150 days post 1 dose***^6,7,8,9,10:

• In Trial 04, Beyfortus demonstrated a relative risk reduction of 60.2% (95% CI: -14.6, 86.2; P=0.09). Primary Cohort: N=1,490 infants ≥35 wGA (placebo: 1.6% [8/496], Beyfortus: 0.6% [6/994])
  • In an exploratory, post hoc analysis of all infants (full study cohort) in Trial 04, Beyfortus demonstrated a relative risk reduction of 76.8% (95% CI: 49.4, 89.4). N=3,012 infants ≥35 wGA (placebo: 2.0% [20/1,003], Beyfortus: 0.4% [9/2,009]) ^8,9
• In Trial 03, Beyfortus demonstrated a relative risk reduction of 78.4% (95% CI: 51.9, 90.3; P=0.0002). N=1,453 infants ≥29 to <35 wGA (placebo: 4.1% [20/484], Beyfortus: 0.8% [8/969]) ^6,10

The most common adverse reactions in Trial 04 and Trial 03 were rash (0.9%) and injection site reactions (0.3%).⁶

An analysis from the CDC earlier this year provided an early estimate of Beyfortus effectiveness for the prevention of RSV-associated hospitalization among infants entering their first RSV season. In the CDC analysis, conducted in 4 out of 7 sites within the New Vaccine Surveillance Network, Beyfortus effectiveness against RSV-associated hospitalization was estimated using a test-negative, case-control study design. The analysis included 699 infants <8 months of age who were hospitalized with acute respiratory illness. Of these, 407 (58%) were case patients with a positive RSV result and 292 (42%) were control patients with a negative RSV result. 6 out of 407 case patients who received Beyfortus were RSV-positive, compared with 53 out of 292 case patients who were negative for RSV.¹¹

Effectiveness was estimated using regression models (adjusted for potential bias), comparing the odds of receipt of Beyfortus among case patients and control patients. Regression models controlled for age, month of illness, enrollment site, and high-risk medical conditions.¹¹

Interestingly, this early estimate analysis found that Beyfortus was 90% effective (95% CI: 75-96) in preventing RSV-associated hospitalization from October 1, 2023, to February 29, 2024, with a median time from receipt to symptom onset of 45 days (interquartile range (IQR) =19-76 days).¹¹

The CDC will continue to monitor Beyfortus effectiveness.

The findings in this report are subject to limitations¹¹:

• A small proportion of hospitalized infants with acute respiratory illness received Beyfortus, likely in part because of delayed availability at the start of the season and intermittent supply shortages, and infants who received.
• Because Beyfortus became available at most sites in the United States after seasonal RSV circulation began, some infants in this analysis might have had an RSV infection before receipt of Beyfortus, which might have affected estimated effectiveness.
• Beyfortus effectiveness was not estimated by dosage because Beyfortus dosage was not ascertained.
• The low number of case patients who received Beyfortus did not allow for stratified estimates by time since receipt of Beyfortus.
• Effectiveness estimate in this report is limited to the prevention of RSV-associated hospitalization and does not include outpatient or emergency department visits.

Helping protect the health of babies through RSV education

As the first touchpoint on the road to parenthood, OB/GYNs, midwives, and family medicine doctors play a pivotal role in guiding expectant parents through the available options to prevent RSV LRTD. We have two exciting interventions to offer this year – a maternal immunization given between 32 and 36 weeks of pregnancy and Beyfortus, the monoclonal antibody that can be given to baby after birth in the hospital or at the pediatrician’s office during a routine visit. Initiating discussions early in pregnancy helps parents-to-be understand the risks of RSV, gives them time to get comfortable with their options and supports them in making an informed decision with confidence.

*Time to maximum concentration is 6 days in adults and uptake half-life is 1.7 days in infants.

**Epidemiology research will further define when local RSV seasons start.

***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.

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

• Hypersensitivity Reactions Including Anaphylaxis: Serious hypersensitivity reactions have been reported following Beyfortus administration. These reactions included urticaria, dyspnea, cyanosis, and/or hypotonia. Anaphylaxis has been observed with human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs and symptoms of anaphylaxis or other clinically significant hypersensitivity reactions occur, initiate appropriate treatment.
• 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.

Ruth Ann Crystal, MD Bio

Dr. Crystal is a board certified, OB/GYN physician entrepreneur with interests in healthcare innovation and human-centered design.

Dr. Crystal has an interest in healthcare startups focusing on the unmet needs of physicians, nurses and patients. At StartX, Stanford’s startup accelerator, Dr. Crystal mentors at startups and is the physician lead for the StartX COVID Task Force since 2020.

¹ Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986;140(6):543-546. doi:10.1001/archpedi.1986.02140200053026

² RSV (Respiratory Syncytial Virus) | CDC. https://www.cdc.gov/rsv/index.html. Accessed July 2024.

³ Arriola CS, Kim L, Langley G, et al. Estimated Burden of Community-Onset Respiratory Syncytial Virus-Associated Hospitalizations Among Children Aged <2 Years in the United States, J Pediatric Infect 2014-15.

⁴ RSV in Infants and Young Children | CDC. https://www.cdc.gov/rsv/high-risk/infants-young-children.html. Accessed April 20, 2022.

⁵ Zhou H, et al. Hospitalizations associated with influenza and respiratory syncytial virus in the United States, Clin Infect Dis. 2012; 54(10):1427-1436.

⁶ Beyfortus (nirsevimab-alip). Prescribing Information. Sanofi.

⁷ Data on file, November 2023.

⁸ Muller WJ, Madhi SA, Nuñez BS, et al. Nirsevimab for prevention of RSV in term and late-preterm infants. N Engl J Med. 2023;388(16):1533-1534.

⁹ Muller WJ, Madhi SA, Nuñez BS, et al. Nirsevimab for prevention of RSV in term and late-preterm infants. N Engl J Med. 2023;388(16)(suppl):1533-1534.

¹⁰ Griffin MP, Yuan Y, Takas T, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med. 2020;383(5):416-425.

¹¹ Moline HL, Tannis A, Toepfer AP, et al. Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus–Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season — New Vaccine Surveillance Network, October 2023–February 2024. MMWR Morb Mortal Wkly Rep 2024;73:209–214.