A panel of FDA’s outside advisors recommended the agency approve GSK’s respiratory syncytial virus (RSV) vaccine for older adults, a day after backing Pfizer’s RSV vaccine candidate for that same population.
By votes of 12-0 on efficacy and 10-2 on safety, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) said the available data support GSK’s RSV prefusion F protein vaccine (RSVPreF3), adjuvanted with AS01Ε, for reducing RSV-related lower respiratory tract infections in adults 60 and older. The vaccine candidate carries a proposed trade name of Arexvy.
“The benefits of this vaccine outweigh the risks, and especially in severe disease, across all of the age groups,” said James Hildreth Sr., MD, PhD, of Meharry Medical College in Nashville, Tennessee. “I feel comfortable if this was to be given.”
But committee members wanted more data, frustrated that the data so far were limited to one season of RSV. AReSVi-006 (Adult Respiratory Syncytial Virus), the ongoing phase III trial that served as primary support for approval, is designed to cover three RSV seasons.
“I would be more comfortable with more years of data,” said Marie Griffin, MD, MPH, of Vanderbilt University Medical Center in Nashville, who voted against the vaccine on safety.
“We have a bad disease, we have a good vaccine … our collective thirst for additional data has no bounds,” said committee member David Kim, MD, of the Department of Health and Human Services.
Panelist Amanda Cohn, MD, of the CDC’s National Center for Immunizations and Respiratory Diseases in Atlanta, pointed out that accruing “more robust data” could help ensure public confidence in the vaccine.
In the long run, that “actually may be better for public health than getting this vaccine out during this season,” she said.
Safety questions surrounding a potential risk for Guillain-Barré syndrome (GBS) spilled over from the day before, though FDA staff reminded the committee that each vaccine was to be evaluated separately. In clinical trials, three cases of GBS were reported as being possibly related to the RSV vaccines, two in the case of Pfizer’s vaccine and one with GSK’s.
Jay Portnoy, MD, of Children’s Mercy Hospital in Kansas City, Missouri, noted that many of the safety events may be attributable to the ASO1Ε adjuvant, the same adjuvant used in GSK’s herpes zoster vaccine (Shingrix).
“I take comfort in the fact that it was used in Shingrix,” he said. During a presentation on Wednesday, GSK noted that its RSV vaccine contains half the amount of the adjuvant.
Discussion also arose over two cases of acute disseminated encephalomyelitis (ADEM), one fatal, in a separate GSK study testing co-administration of the RSV vaccine with a quadrivalent influenza vaccine. In a pre-meeting briefing document, FDA reviewers concluded that it considered the cases “possibly related” to either the RSV or flu vaccine.
AReSVi-006 included 24,960 adults age 60 and older who were randomized 1:1 to the vaccine or placebo. Interim data showed that a single dose yielded a vaccine efficacy of 82.6% against RSV-associated lower respiratory tract illness (96.95% CI 57.9-94.1), meeting the study’s primary endpoint, and vaccine efficacy landed at 94.1% against severe RSV illness (95% CI 62.4-99.9).
For the primary endpoint, the vaccine performed similarly across RSV subgroups and age groups.
Serious adverse events were rare in the phase III trial, with just six in the vaccine arm and five in the placebo arm. Deaths occurred in 0.4% of the vaccine recipients and 0.5% of those receiving placebo, with none considered to be related to the intervention.
Six cases combined of potential immune mediated diseases were deemed possibly related to the RSV vaccine by FDA staff: Bell’s palsy, pancytopenia, Graves’ disease, gout, and psoriasis.
Currently, there are no approved vaccines 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.
While the FDA is not required to follow the advice of its advisors, it typically does.