Abstract
BACKGROUND: Data describing respiratory syncytial virus (RSV) neutralizing antibody (nAb) levels for nirsevimab, a recently approved, extended half-life, anti-RSV fusion protein (F protein) monoclonal antibody, relative to the previous standard of care, palivizumab, have not been reported. METHODS: MEDLEY was a randomized, palivizumab-controlled, phase 2/3 study of nirsevimab during 2 RSV seasons (season 1 and 2) in infants born preterm (#35 weeks’ gestational age; dosed season 1 only) or with congenital heart disease or chronic lung disease of prematurity (dosed seasons 1 and 2). Participants were randomly assigned to receive a single dose of nirsevimab followed by 4 monthly placebo doses, or 5 once-monthly doses of palivizumab. Anti-RSV F protein serology (ie, levels of prefusion [pre-F]/postfusion [post-F] conformation antibodies), nirsevimab and palivizumab concentrations, and RSV nAbs were measured in participant serum collected at baseline (pre-dose) and days 31, 151, and 361. RESULTS: Serologic data were similar in seasons 1 and 2. Nirsevimab predominately conferred pre-F antibodies, whereas palivizumab conferred pre-F and post-F antibodies. Nirsevimab and palivizumab serum concentrations highly correlated with nAb levels in both seasons. In season 1, nAb levels in nirsevimab recipients were highest in day 31 samples and gradually declined but remained 17-fold above baseline at day 361. nAb levels in palivizumab recipients increased incrementally with monthly doses to day 151. nAb levels followed similar patterns in season 2. nAb levels were ∼10-fold higher with nirsevimab compared with palivizumab across both seasons. CONCLUSIONS: Nirsevimab prophylaxis confers ∼10-fold higher and more sustained RSV nAb levels relative to palivizumab.
| Original language | English (US) |
|---|---|
| Article number | e2024067174 |
| Journal | Pediatrics |
| Volume | 154 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2024 |
Funding
We thank the MEDLEY trial participants and their families, members of the investigator teams, and the full clinical team at AstraZeneca. We would like to thank PPD Vaccines, Richmond, Virginia, for their assistance in developing the RSV multiplex serology assay and measuring anti-RSV nAbs, as reported in this article. The authors acknowledge Rebecca A. Bachmann, PhD, of AstraZeneca, for facilitating author discussion and providing strategic advice and critical review of this manuscript. Medical writing support was provided by Craig O\u2019Hare, PhD, of Ashfield MedComms, an Inizio company, which was in accordance with Good Publication Practice 2022 guidelines (https://www.ismpp.org/gpp-2022; Ann Intern Med. 2022 doi:10.7326/M22-1460) and funded by AstraZeneca. The MEDLEY trial was funded by AstraZeneca and Sanofi. Nirsevimab is being developed and commercialized in partnership between AstraZeneca and Sanofi. All authors and authors employed by the sponsor contributed to the trial concept, design, conduct, and interpretation of data. Trial site investigators contracted by the sponsor contributed to data collection, analysis, and interpretation. The first draft of the manuscript was written by a medical writer funded by the trial sponsors under the direction of all the authors. The decision to submit the manuscript for publication was made by all authors, including those employed by the sponsor: Deidre Wilkins, Ulrika W\u00E4hlby Hamr\u00E9n, and Tonya Villafana.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health