A study was published recently by the New England Journal of Medicine, that reported on the former investigational candidate, RSV prefusion F protein–based maternal vaccine (RSVPreF3-Mat, GSK), and the specifics which led to the decision to stop development on it. Specifically, the vaccine was found to be efficacious, but raised a safety concern, leading to the trial to be halted.
“The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine,” the investigators wrote in the published paper.
Study Parameters
As part of RSV MAT-009 trial, investigators conducted a phase 3 study involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat. They included 2 cohorts: 3426 infants in the vaccine group; and 1711 in the placebo group. They were all followed from birth to 6 months of age.
The study participants were randomly assigned in a 2:1 ratio to receive RSVPreF3-Mat vaccine or placebo between 24 weeks 0 days and 34 weeks 0 days of gestation. They identified the primary outcomes as severe medically assessed RSV-associated lower respiratory tract disease in infants from birth to 6 months of age and safety in infants from birth to 12 months of age.
After the observation of a higher risk of preterm birth in the vaccine group than in the placebo group, enrollment and vaccination were stopped early, and exploratory analyses of the safety signal of preterm birth were performed.
What You Need to Know
The investigational candidate RSV prefusion F protein–based maternal vaccine (RSVPreF3-Mat, GSK) showed efficacy in reducing the risk of medically assessed RSV-associated lower respiratory tract disease among infants.
Despite the positive efficacy results, safety concerns emerged during the trial. The study observed a higher risk of preterm birth among infants born to mothers who received the RSVPreF3-Mat vaccine compared to those who received the placebo. This safety signal led to the decision to halt the trial prematurely. The relative risk of preterm birth was 1.37 times higher in the vaccine group than in the placebo group.
Due to the observed safety concern regarding preterm birth and the imbalance in neonatal death rates, the manufacturer of the vaccine, GSK, decided to halt the development of the RSVPreF3-Mat vaccine in February 2022.
Study Results
The investigators did identify a favorable efficacy in the vaccine group. “Between birth and 6 months of age, medically assessed RSV-associated lower respiratory tract disease occurred in 16 infants in the vaccine group and in 24 infants in the placebo group (vaccine efficacy, 65.5%; 95% credible interval, 37.5 to 82.0), and severe medically assessed RSV-associated lower respiratory tract disease occurred in 8 and 14 infants, respectively (vaccine efficacy, 69.0%; 95% credible interval, 33.0 to 87.6),” the investigators wrote.
And with the preterm birth risk, the investigators reported there was a slight increase over the placebo group’s results.
“Preterm birth occurred in 6.8% of the infants (237 of 3494) in the vaccine group and in 4.9% of those (86 of 1739) in the placebo group (relative risk, 1.37; 95% confidence interval [CI], 1.08 to 1.74; P=0.01); neonatal death occurred in 0.4% (13 of 3494) and 0.2% (3 of 1739), respectively (relative risk, 2.16; 95% CI, 0.62 to 7.56; P=0.23), an imbalance probably attributable to the greater percentage of preterm births in the vaccine group,” the investigators wrote. They also said there were no other safety signals observed.
The vaccine’s manufacturer, GSK, stopped the development of this maternal RSV vaccine in February 2022.
Interested in learning more about the clinical considerations or RSV vaccine recommendations? Check out our series, RSV: A New Era in Prevention, which also includes a roundtable of clinicians who discuss the new vaccines and immunizations.
Reference
Dieussaert I, Hyung Kim J, Luik S, et al. RSV Prefusion F Protein-Based Maternal Vaccine - Preterm Birth and Other Outcomes. N Engl J Med. 2024;390(11):1009-1021. doi:10.1056/NEJMoa2305478
