Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants
Eric A F Simões, Eduardo Forleo-Neto, Gregory P Geba, Mohamed Kamal, Feng Yang, Helen Cicirello, Matthew R Houghton, Ronald Rideman, Qiong Zhao, Sarah L Benvin, Alicia Hawes, Erin D Fuller, Elzbieta Wloga, Jose M Novoa Pizarro, Flor M Munoz, Scott A Rush, Jason S McLellan, Leah Lipsich, Neil Stahl, George D Yancopoulos, David M Weinreich, Christos A Kyratsous, Sumathi Sivapalasingam, Eric A F Simões, Eduardo Forleo-Neto, Gregory P Geba, Mohamed Kamal, Feng Yang, Helen Cicirello, Matthew R Houghton, Ronald Rideman, Qiong Zhao, Sarah L Benvin, Alicia Hawes, Erin D Fuller, Elzbieta Wloga, Jose M Novoa Pizarro, Flor M Munoz, Scott A Rush, Jason S McLellan, Leah Lipsich, Neil Stahl, George D Yancopoulos, David M Weinreich, Christos A Kyratsous, Sumathi Sivapalasingam
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.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
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Source: PubMed