A committee of independent expert advisors for the Food and Drug Administration on Thursday voted largely in favor of the agency approving Pfizer’s vaccine for protecting infants from the common respiratory virus RSV—respiratory syncytial (sin-SISH-uhl) virus—which can be deadly to infants.
The vaccine, provisionally dubbed Abrysvo, is given to pregnant people between 24 and 36 weeks of pregnancy, allowing protective antibodies to develop and then cross the placenta to protect the fetus.
In a phase III trial involving nearly 7,400 pregnant people in 18 countries, the vaccine was nearly 82 percent effective at preventing severe RSV disease in the first 90 days of a baby’s life. It was 69 percent effective at 180 days. In terms of protecting against non-severe respiratory disease from RSV, the trial results didn’t meet the statistical criteria to find efficacy at 90 days, but data from 180 days suggested an efficacy of around 51 percent.
In the first of two votes in today’s day-long meeting, the FDA advisors voted unanimously, 14 to 0, that the efficacy data looked good and suggested the vaccine would protect infants from RSV.
But the safety data, which was the focus of the second vote, gave some of the members pause. While the vaccine appeared largely safe for pregnant people and infants compared with a placebo, data from a phase II trial and the phase III trial included a faint signal suggesting the vaccination could increase the risk of pre-term birth. In the phase III trial, there were 201 infants born premature (earlier than 37 weeks) in the vaccination group, while there were only 169 premature babies in the placebo group. Among these early births, 21 in the vaccination group were early premature births (before 34 weeks), while there were only 12 early premature births in the placebo group.
The differences overall weren’t statistically significant, and the rates of prematurity were lower than what’s seen in the general population usually. But, as several of the FDA advisors noted, the phase III trial wasn’t set up to address this signal, despite being seen in the earlier phase II trial. There was also an imbalance of where the signal was seen; Pfizer representatives emphasized that there was no difference in premature births in trial participants in high-income countries, including the US.
Concerns, but mostly excitement
Alone, this data blip may not have been enough to raise concerns. But it worried some advisors, who noted that GSK, another pharmaceutical giant, developed its own RSV vaccine and encountered the same signal. GSK had a vaccine of a similar design and dose that was similarly given to pregnant people in the same 24- to 36-week window of pregnancy. In its phase III trial, GSK saw a statistically significant increase in pre-term births. And the company dropped the trial because of it.
It’s a big deal when a pharmaceutical company abandons a trial, Dr. Paul Offit, professor of pediatrics at The Children’s Hospital of Philadelphia, noted in the discussion section of the meeting. “Those decisions are never made lightly,” Offit said.
When the vote came on whether the safety data for the vaccine was adequate, it was a 10 to 4 breakdown, with Offit among the four who voted “no.” After the vote, he reiterated that the data presented by Pfizer didn’t assuage his concerns about the GSK findings. “If you’re in any sense risking premature births with this vaccine, I think there’ll be a big price to pay,” he warned.
But most of the panel was less bothered by the uncertainty of the premature birth signal, and some expected it would reveal itself to be a statistical anomaly, lost when the vaccine is given to larger numbers. Some members also noted that the trial data on birth weights and similar rates of developmental delays were reassuring that the vaccine was safe. Pfizer outlined a post-market surveillance system to try to track such outcomes.
Overall, many advisors were enthusiastic about the vaccine’s potential. The efficacy is “very exciting,” Amanda Cohn, director of the division of birth defects and infant disorders at the Centers for Disease Control and Prevention, said after voting “yes” for both the efficacy and the safety questions. This is “a really important tool for prevention, [I’m] very excited.”
In the US, RSV is among the leading causes of hospitalization for children under 5 years old. In a typical RSV season, the virus sends between 58,000 and 80,000 children under 5 to the hospital, and between 100 to 300 die from the infection, the CDC estimates.
The FDA will now decide whether to approve the vaccine. If it does, the CDC will weigh in with recommendations for its use in the US.