The pharmaceutical giant GlaxoSmithKline (GSK) abandoned a maternal vaccine because there was an unexplained higher incidence of preterm birth among infants whose mothers received the shot, the company has disclosed in a new study.
Among women who received GSK’s respiratory syncytial virus (RSV) vaccine, known as RSVPreF3-Mat, during pregnancy, 237 had infants born prematurely. Just 89 in the placebo group suffered the same problem.
Of the vaccinated women, 6.8 percent had infants born prematurely, compared with 4.9 percent of women who received a placebo, researchers reported in the New England Journal of Medicine.
“For every 54 infants born to women who received RSVPreF3-Mat rather than placebo during pregnancy, one additional preterm birth occurred,” the researchers said.
If the phase III trial results had been better, it would have likely been the last test before regulatory approval.
Researchers were unable to determine why infants of vaccinated women were more likely to be born prematurely.
“The intervals from vaccination to preterm delivery generally ranged from weeks to months, which suggests the absence of a direct effect of vaccination on mechanisms that initiated preterm birth,” they said.
“Although inflammatory processes have been associated with premature birth, post hoc analyses in the current trial showed no association between cytokine levels in maternal participants (as assessed in serum samples obtained before and 1 month after vaccination) and preterm birth. However, blood samples were not obtained soon enough after vaccination to reliably detect vaccine-related increases in cytokine levels.”
Investigators also found that seven infants who were born preterm and whose mothers received a shot died. Zero preterm infants whose mothers received a placebo died.
Data from the trial suggest that “any between-group difference in the incidence of neonatal death was attributable to the higher incidence of preterm birth in the vaccine group than in the placebo group,” the researchers said.
The numbers came from data at day 43 after birth from 3,494 infants whose mothers were vaccinated and 1,739 infants whose mothers were in the placebo group.
The efficacy results indicated that the vaccine could be successful, with a significantly lower percentage of infants of vaccinated women contracting RSV-associated lower respiratory tract disease and severe RSV-associated lower respiratory tract disease, according to the researchers.
The results “suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower in the vaccine group than in the placebo group but that the risk of preterm birth was higher in the vaccine group,” they said.
The results shed more light on why GSK announced in 2022 that it was pausing enrollment and vaccination in multiple trials for the maternal RSV vaccine over safety concerns. The pause was later turned into a halt in enrollment and vaccination.
Apart from preterm birth, no other safety signals were observed in the trial, according to the researchers, including Dr. Philip Dormitzer, a GSK employee.
Limitations of the trial included that it became unblinded, potentially changing efficacy and safety outcomes.
The FDA has also approved two RSV vaccines—one from Pfizer and one from GSK—for people aged 60 and older.
RSV is a respiratory virus that causes symptoms such as coughing and wheezing. According to the U.S. Centers for Disease Control and Prevention, nearly all children will have been infected by RSV by age 2.
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