FDA Advisory Committee Recommends Approving First-Ever RSV Vaccine

Today, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted in favor of the safety and efficacy of Pfizer’s respiratory syncytial virus (RSV) vaccine candidate. If the US Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) abide by this recommendation, the vaccine, Abrysvo (RSVpreF), could become the first ever RSV vaccine.

Today was the first of 2 back-to-back VRBPAC sessions. Contagion will also be covering tomorrow’s meeting and subsequent vote regarding GSK’s RSV vaccine candidate.

The recommendation was admittedly reluctant, with many VRBPAC members wishing there were more data to inform their vote.

The VRBPAC Vote

At the end of the February 28 meeting, VRBPAC was instructed to vote “Yes” or “No” on the following 2 voting questions:

1. Are the available data adequate to support the safety of ABRYSVO (RSVpreF) when administered to individuals 60 years of age and older for the prevention of lower respiratory tract disease caused by RSV?
2. Are the available data adequate to support the effectiveness of ABRYSVO (RSVpreF) for the prevention of lower respiratory tract disease caused by RSV in individuals 60 years of age and older?

For both the first and second voting questions, 7 of 12 VRBPAC members voted yes, with 4 no’s and 1 abstention. One member who voted no, Dr. Marie Griffin, said the rate of 1 in 9000 participants developing Guillain-Barre syndrome (GBS) after RSVpreF vaccination was a safety concern. Griffin and other naysayers expressed hesitancy due to the lack of data analyzing the safety of coadministering Pfizer’s RSV vaccine with other vaccines.

It is notable that unlike past vaccine recommendations, VRBPAC was not unanimous in their vote. Indeed, several committee members voiced their disappointment that there was not more data. However, the “yes” voters affirmed that they felt RSVpreF met the criteria established by the voting questions.

RSV Virology and Illness Profile

Natalie Thornburg, PhD, of the CDC’s Coronaviruses and Other Respiratory Viruses Division, gave an overview of the complications of RSV and its subtypes. Thornburg explained the virology of RSV and its strain variations, before delineating the CDC’s surveillance measures.

The next presenter, Fiona Havers, MD, MHS, FIDSA, CDC team lead of the RESP-NET Hospitalization Surveillance Team, noted that RSV surveillance statistics do not accurately represent the number of infections.

“RSV is underdetected, as RSV testing is often not performed, even in hospitalized patients,” Havers explained. “And this is understandable, because as of now, there is currently no vaccine or recommended treatment for most RSV cases.”

Although most people who experience severe RSV disease are in their 70s or 80s, Havers showed this is complicated by social determinants of health, including race and ethnicity. “Generally speaking,” she said, “in younger age groups, there’s a higher proportion of Black and Hispanic patients.”

Havers’s presentation also demonstrated that severe RSV disease is most prevalent in individuals who are immunocompromised or have a comorbid condition.

H. Keipp Talbot, MD, MPH, FIDSA, an associate professor at Vanderbilt University Medical Center, discussed the clinical considerations of RSV in older adults. Keipp clarified that most children are exposed to RSV within their first 2 years, “So all the infections that we will be discussing in adults will be reinfections.”

Pfizer RSVpreF Safety and Efficacy Data Presentation

After initial data presentations covering RSV virology and illness severity, Pfizer representatives shared trial results from their Abrysvo (RSVpreF) vaccine candidate. Pfizer vice president of Vaccine Clinical Research and Development, Alejandra Gurtman, MD, FIDSA, gave the sponsor presentation, entitled “Safety and Efficacy of Bivalent RSV Prefusion F Vaccine in Adults ≥60 Years of Age.”

Pfizer’s safety data suggested their RSVpreF vaccine candidate was safe and well tolerated; local and systemic reactions were mostly mild-to-moderate and did not last long. Additionally, the adverse event profile “did not suggest any safety concerns for RSVpreF vaccination in adults 60 years of age and older,” said Gurtman. “The benefit-to-risk ration is highly favorable and supports the proposed indication.”

Pfizer’s proposed indication is as follows: “Prevention of acute respiratory disease and lower respiratory tract disease caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older by active immunization.”

Gurtman concluded that RSVpreF was highly efficacious in reducing RSV-associated lower respiratory tract infection (LRTI) and acute respiratory infection (ARI) in adults 60 years and older. Notably, vaccine efficacy was consistent across population subgroup analyses and across RSV subgroups A and B.

A 0.5 mL dosage of the intramuscularly administered RSVpreF vaccine contains 60 mcg of lyophilized recombinant prefusion F protein from both RSV-A and RSV-B subgroups expressed in CHO cells, 120 mcg of total protein.

In the pivotal study of RSVpreF, 17215 participants aged ≥60 years received a single 120 µg dose of the vaccine. RSVpreF was determined to be 66.7% effective at preventing LRTI-RSV with 2 or more symptoms, and 85.7% effective at preventing LRTI-RSV with 3 or more symptoms. The vaccine efficacy against a first episode of ARI-RSV was 62.1%.

Come back tomorrow for our coverage of the VRBPAC meeting and vote to recommend GSK’s RSV vaccine.