Nirsevimab for the prevention of RSV in infants

 by Ioanna Barkas, MD (’24)

 

The FDA recently approved the availability of Nirsevimab (trade name of Beyfortus) for the 2023-2024 viral season for the prevention of RSV lower respiratory tract disease in infants. Given the novelty of this prophylaxis and the media coverage of RSV, we will receive questions from parents regarding the efficacy and safety of Nirsevimab.  This is a summary of the CDC guidelines and
our current institutional guidelines for nirsevimab prophylaxis as well as a
summary of the Melody III clinical trial assessing safety and efficacy of
Nirsevimab in infants.

 What is Nirsevimab?

Nirsevimab is not a vaccine. It is a long
acting monoclonal antibody against the RSV fusion protein which is required for
entry into human cells.

 What are the AAP & CDC recommendations? 2,3

Nirsevimab should be offered to:

   All infants who are born during
the RSV season

   All infants who are <8months of
age at the start of RSV season

   Infants who are 8-19 months at the
start of RSV season and meet any of the following criteria:

   Diagnosis of CLD requiring chronic
steroids, diuretics or supplemental oxygen in the prior 6 months

   Diagnosis of CF with prior
hospitalization or persistent abnormalities on chest imaging OR
weight-for-length below 10th percentile

   American Indian or Alaskan native
children

   If determined by provider to
be  high risk for severe RSV disease

 

Nirsevimab SHOULD NOT be offered to:

   A newborn whose mother received
the RSV vaccine between 32-36 weeks and at least 2 weeks prior to delivery
(unless mother is immunocompromised or baby underwent cardiac bypass or ECMO)

   Any infant who has a history of a
serious hypersensitivity reaction to any of the active

 

Dosing guide:

Infants weighing <5 kg: 50 mg dose

Infants weighing ≥5 kg: 100 mg dose

Children receiving Nirsevimab in their second
RSV season: 200 mg dose administered through 2 separate 100 mg IM injections

 What did the clinical trial show & how robust was the
data?

The MELODY trial was a double-blind, placebo controlled trial to evaluate safety and efficacy of  nirsevimab for the prevention of RSV.  Infants included in the trial were born at or later than 35 weeks gestation and enrolled during or entering their first RSV season. The major results of the trial included efficacy of 77% of a single nirsevimab injection for medically attended RSV associated lower respiratory tract infection with a NNT (number needed to treat)  of 12 (95% confidence interval 59.8 to 86.8) and a significant p value of <0.001. Efficacy for hospitalization for any respiratory illness due to RSV was 61.1% with a NNT of 62 (95% confidence interval of -3.7 to 85.4). Given large confidence interval that crosses zero, later result is not significant. The adverse event profile was very similar among recipients who received nirsevimab and those who received the placebo. The adverse events that were reported included recurrent vomiting, hypoglycemia and anemia all attributed to other underlying diagnoses and three deaths all attributed to other causes. The one adverse event of significance identified by the researchers was a grade 3 generalized macular rash with no associated systemic symptoms that appeared on day 6 post injection and resolved by day 201 . There were no reported cases of serious hypersensitivity reactions or anaphylaxis.

Overall, the clinical data that was most robust for the MELODY trial and the data that we can use tocounsel patients in clinic is the efficacy for hospitalization for any respiratory illness- 1 in 12 infants who received a single dose of nirsevimab
prior to the RSV season did not require hospitalization for an RSV associated
respiratory illness.

References

1)    Hammitt LL, Dagan R,
Yuan Y, Baca Cots M, Bosheva M, Madhi SA, Muller WJ, Zar
HJ, Brooks D,
Grenham A, Wählby Hamrén U, Mankad VS, Ren P, Takas T, Abram ME, Leach A,
Griffin MP, Villafana T; MELODY Study Group. Nirsevimab for Prevention of RSV
in Healthy Late-Preterm and Term Infants. N Engl J Med. 2022 Mar
3;386(9):837-846. doi: 10.1056/NEJMoa2110275. PMID: 35235726.

2)   
Lifespan Pharmacy
Beyfortus/Nirsevimab guidelines, 2023 

3)     Jones JM, Fleming-Dutra KE, Prill MM, et al.
Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease
Among Infants and Young Children: Recommendations of the Advisory Committee on
Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep
2023;72:920–925. DOI:
http://dx.doi.org/10.15585/mmwr.mm7234a4