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In two somewhat close votes, an FDA panel of outside experts recommended the agency approve Pfizer's respiratory syncytial virus (RSV) vaccine for older adults, despite concerns over the potential risk for Guillain Barré syndrome.

By a tally of 7-4 for safety and efficacy (with one abstention in each case), the Vaccines and Related Biological Products Advisory Committee (VRBPAC) said the evidence favors the RSV prefusion F protein vaccine (RSVPreF) -- which carries a proposed trade name of Abrysvo -- for reducing RSV-related lower respiratory tract infections in adults 60 and up.

However, VRBPAC members showed reservations ranging from the largely health study population, rather than the more vulnerable group of older adults who need the vaccine most, to the limited number of events for the main outcomes.

"One or two cases in the opposite directions could have change the results," said Jay Portnoy, MD, of Children's Mercy Hospital in Kansas City, Missouri, who voted yes on safety but no on efficacy. "I think it's rushed. I would really have liked to see them complete the study, get another year's worth of RSV data."

"There are too many lingering questions in this data set," said Steven Pergam, MD, of the Seattle Cancer Care Alliance Seattle, who split his votes the same way.

"I'm really struggling with this because of the importance about this vaccine to public health," said Pergam, adding that the study "did not target the population of interest."

VRBPAC Chair Hana M. El Sahly, MD, of Baylor College of Medicine in Houston, noted that the population enrolled was not enriched for chronic obstructive pulmonary disease (COPD) and heart failure.

"These are the individuals that would have had significant disease with this virus," said El Sahly, who voted yes for efficacy but no on safety.

Despite the safety signal for Guillain Barré syndrome, Daniel Feikin, MD, MSPH, a respiratory disease consultant in Coppet, Switzerland, voted in favor of the vaccine for both safety and efficacy.

"I can't help but think about the risk-benefit analysis and ratio of the amount of disease that could potentially be prevented by this vaccine," he said.

Currently, no vaccines exist to protect against RSV infection. According to data from the CDC, an estimated 177,000 older adults in the U.S. were hospitalized due to RSV infections in 2017 alone, and 14,000 died.

Primary support for RSVPreF came in the form of the phase III RENOIR trial, which included 34,284 participants age 60 and up randomized to either a single intramuscular injection dose of vaccine (120 µg) or placebo.

Vaccine efficacy at an interim analysis reached 66.7% against two or more lower respiratory tract RSV symptoms (96.66% CI 28.8-85.8) and 85.7% against three or more symptoms (96.66% CI 32.0-98.7), meeting the co-primary endpoints of the study.

Holly Janes, PhD, of Fred Hutchinson Cancer Research Center in Seattle, pointed out that efficacy was based on just 44 cases of RSV in total.

But "I was swayed by the high estimates of efficacy, consistent estimates of efficacy across subgroups and the fact that the lower bounds of the confidence intervals were not just above 20%, but above 30%," said Janes, who voted in favor of both the vaccine's safety and efficacy.

During the meeting on Tuesday, Pfizer presented updated efficacy data that included an entire RSV season, which showed largely similar results, a small dip in efficacy for RSV with two or more symptoms but a slight uptick in efficacy for RSV cases with three or more symptoms.

Another concern raised by panelists were the two cases of Guillain-Barré syndrome in the vaccination group, which FDA reviewers flagged ahead of the meeting.

In the U.S. each year, it's estimated that roughly 1.5-3.0 cases of the rare neurological disorder occur per 100,000 people age 60 and older. But in the trial, the two cases both occurred within 2 weeks of vaccination.

"No matter what the background rates, you have to think in terms of the rates within a few weeks rather than within a year," said Marie Griffin, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee. "It seems to me, one case is a red flag, two cases is very concerning."

The FDA said that if approved, it would require enhanced pharmacovigilance for Guillain-Barré syndrome, along with a post-marketing study to further assess immune-mediated demodulating conditions.

Feikin said this postmarketing surveillance will be very important to monitor for safety as a larger population receives the vaccine.

Safety signals also included atrial fibrillation (10 events in the study group and four with placebo), and an event of hypersensitivity in the vaccine group. Serious adverse events occurred in 2.3% of each group, while deaths occurred in 0.3% of each group, with none considered related to the study intervention.

Given the limited follow-up duration of the trial to date, data are not yet available on the durability of the vaccine, or how effective the vaccine is in frail or immunocompromised individuals, or against severe illness.

While the FDA is not required to follow the recommendations of its advisors, it typically does.

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