2. Academic Validation
  3. Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants

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

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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