FDA Panel Backs Pfizer’s Maternal RSV Vaccine Despite Safety Concerns
Pictured: Syringe pulling vaccine from a vial / Adobe Stock, weyo
Pfizer swept the efficacy vote and scored a 10-4 safety verdict, as outside experts voted that the data it submitted in its Biologics License Application support the effectiveness and safety of the vaccine in preventing severe disease in babies born to mothers vaccinated during pregnancy.
Overall, the data package spanned five clinical trials where more than 4,100 expectant mothers were dosed with the candidate, which will be known as Abrysvo if approved.
The verdict followed presentations from Pfizer, CDC scientists and the FDA. Panelists asked questions about the significance of a numerical imbalance in the number of preterm births in the vaccine group compared to placebo, according to Endpoints News. Saad Omer, director of the Yale Institute for Global Health, called this imbalance “the elephant in the room” during deliberations, according to Endpoints.
Amanda Cohn, director of the CDC’s division of birth defects and infant disorders, said that, on balance, she was comfortable voting in favor of the vaccine, according to STAT News. Even infants born preterm will benefit from the antibodies they would get in utero from the vaccine, she said.
The FDA is not required to follow VRBPAC’s guidance, though it often does. The regulator is expected to make a decision before the end of August.
Original story, published May 18:
FDA Shows Confidence in Pfizer’s Maternal RSV Shot Ahead of Panel
Abrysvo, Pfizer’s investigational vaccine for respiratory syncytial virus infection, appears to be safe and effective in the pediatric setting, according to the FDA’s briefing document published ahead of an advisory committee meeting.
The agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will convene Thursday to examine the risk-benefit profile of Abrysvo, which Pfizer is proposing to administer to mothers during their second or third trimester of pregnancy to immunize children from birth through six months of age.
Pfizer is backing Abrysvo’s Biologics License Application with data from five clinical trials, totaling more than 4,100 mothers dosed with the candidate. The company’s own briefing document showed that Abrysvo achieved a vaccine efficacy of 81.1% against laboratory-confirmed severe medically-attended lower respiratory tract infection (MA-LRTI) through 90 days after birth. By day 180, the candidate’s efficacy estimate remained high at 69.4%.
As for safety, Pfizer documented mostly mild or moderate local and systemic adverse reactions among inoculated mothers. Serious adverse events, stillbirths and fetal deaths were uncommon in general and were balanced between the treated and placebo groups.
Abrysvo was likewise safe for infants, with similar rates of adverse side effects, including preterm birth, low biirth weight and developmental delays, occurring in both vaccinated and placebo groups.
These data point to Abrysvo’s “favorable benefit/risk profile,” Pfizer wrote in the briefing document, adding that active immunization in pregnant mothers could strongly suppress severe MA-LRTI in infants and, in turn, “has the potential to have an impact on reducing global infant mortality due to RSV.”
Concerns with Safety Data
In the FDA’s analysis of Pfizer’s data, its reviewers cited Abrysvo’s “successful vaccine efficacy for prevention of severe [lower respiratory tract disease] caused by RSV in infants.”
However, the agency also flagged an “imbalance in the percentage of premature infants” in one of the Abrysvo studies. In this Phase III, randomized, double-blinded and placebo-controlled trial, 5.7% of infants in the Abrysvo group were born preterm, as opposed to 4.7% among placebo comparators.
This 1% difference was not statistically significant, and most premature births were still near term. In the Abrysvo arm, 5% of all live births were within 34 and 37 weeks of gestation. Moreover, only one infant in each study arm was born extremely prematurely.
“The safety data appear generally favorable for vaccine administration, and we noted potential uncertainty based on the numerical imbalance in premature deliveries,” the FDA’s reviewers wrote, adding that the VRBPAC should take this into consideration as the external experts vote on whether Pfizer’s data support a “favorable risk analysis” of Abrysvo.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at firstname.lastname@example.org or email@example.com.