Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants

  • Clin Infect Dis. 2021 Dec 6;73(11):e4400-e4408. doi: 10.1093/cid/ciaa951.
Eric A F Simões  1 ,  Eduardo Forleo-Neto  2 ,  Gregory P Geba  2 ,  Mohamed Kamal  2 ,  Feng Yang  2 ,  Helen Cicirello  2 ,  Matthew R Houghton  2 ,  Ronald Rideman  2 ,  Qiong Zhao  2 ,  Sarah L Benvin  2 ,  Alicia Hawes  3 ,  Erin D Fuller  3 ,  Elzbieta Wloga  2 ,  Jose M Novoa Pizarro  4 ,  Flor M Munoz  5 ,  Scott A Rush  6 ,  Jason S McLellan  6 ,  Leah Lipsich  2 ,  Neil Stahl  2 ,  George D Yancopoulos  2 ,  David M Weinreich  2 ,  Christos A Kyratsous  2 ,  Sumathi Sivapalasingam  2
Affiliations
  • 1. Department of Pediatrics, University of Colorado School of Medicine, and The Children's Hospital Colorado, Aurora, Colorado, USA.
  • 2. Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USA.
  • 3. Regeneron Genetics Center, Tarrytown, New York, USA.
  • 4. Facultad Medicina Universidad del Desarrollo/CAS, Hospital Padre Hurtado, Santiago, Chile.
  • 5. Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
  • 6. Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
PMID: 32897368 DOI: 10.1093/cid/ciaa951
Abstract

Background: Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory Infection (MARI).

Methods: We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract Infection (LRTI).

Results: There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks, .38; 95% confidence interval [CI], .14-1.05 in the 1-dose group and .39 [95% CI, .14-1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI, .73-2.56] in the 1-dose group and 1.69 [95% CI, .92-3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2-amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups.

Conclusions: Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts.

Clinical trials registration: NCT02325791.

Keywords
efficacy; infants; respiratory syncytial virus; safety.
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