Unanimous thumbs up from FDA committee for Moderna booster

Regulatory NewsRegulatory News | 14 October 2021 |  By 

An advisory committee to the US Food and Drug Administration (FDA) voted unanimously to recommend a half-strength booster dose of the mRNA COVID-19 developed by Moderna and the National Institutes of Health for those 65 years and older, and for certain younger populations at high risk of severe COVID-19.
Moderna has requested an emergency use authorization (EUA) for the 50 mcg booster dose for individuals who have already completed the two-dose series of the Moderna vaccine; the booster would be delivered at least 6 months after the initial series has been completed.
All 19 voting members of Thursday’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC) voted for boosters for the over-65 population as well as for individuals aged 18-64 years with health conditions that put them at risk for severe COVID-19 disease, or those with occupational or institutional exposure that puts them at risk for serious complications from COVID-19.
However, in a discussion question that was not put to a vote, the committee also expressed uniform reservations about extending Moderna boosters to the general adult population. “I am not so sure that the epidemiology in the US right now supports boosters,” said VRBPAC member Archana Chatterjee, dean of the Chicago Medical School and a pediatric infectious disease expert. She was loathe to place her confidence in Israeli data that showed cases plummeting along with the rollout of boosters to progressively younger age groups, noting that new COVID-19 cases are also falling in the US, where there is no broad booster campaign.
Chatterjee, along with others, expressed concern about the small datasets presented by Moderna in support of its EUA submission. VRBPAC member Paul Offit, a vaccines expert and professor of pediatrics at the Children’s Hospital of Philadelphia, said, “I agree completely with Dr. Chatterjee about going down the path of approving boosters based completely on data from Israel.”
Offit, also a member of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (CDC’s ACIP), also voiced concern that a strong emphasis on boosters may be sending ”the wrong messages” to the general public about the importance of vaccinating the unvaccinated, who still continue to be the primary occupants of intensive care units across the country.
Some committee members bemoaned the lack of a firm correlate of protection they could use as a guide for when boosters would be needed. Doran Fink, deputy director in CBER’s Office of Vaccines, responded to such a query: “Boy, I wish I could tell you what FDA thinks is the correlate of protection. That would make all our lives so much easier, wouldn’t it?”
The agency still doesn’t have enough data to understand which specific antibody thresholds or other correlates can be used in COVID-19, Fink said, adding that immunobridging studies are the technique to rely on at this stage of the public health emergency of the pandemic.
Before either Moderna or FDA presented data, the committee heard data from Israel showing steep declines in cases as boosters were rolled out amid a fifth wave of the Israeli pandemic. Notably, the Israeli data also showed a nearly 6-fold reduction in the rates of severe disease for those aged 60 years and up who had received a booster shot. Most Israelis have received the Pfizer initial series and booster, though some Moderna doses have also been administered.
Data presented by Moderna looking at “early” and “late” recipients of the 2-dose vaccine series showed a higher incidence of breakthrough COVID-19 cases in the early vaccinees. Looking at breakthrough cases in July and August 2021, when the SARS-CoV-2 delta variant predominated in the US, early vaccinees were 36.4% more likely to experience a breakthrough case, with 77.1 cases per 1,000 person-years, compared with 49 cases per 1,000 person-years in the late vaccinee group.
Immunogenicity data were presented in several different ways by FDA and Moderna, but the ability of a booster to bolster antibody titers was not in question. Safety data were similarly overall reassuring, with no serious adverse events or deaths seen in the 344 patients studied for the booster dose EUA submission.
FDA also presented surveillance updates from its Biologics and Effectiveness Safety (BEST) system, which looked at over 12,000,000 doses of Pfizer vaccine and 8,000,000 Moderna doses. Incidence rates of myocarditis or pericarditis within 7 days after receipt of either vaccine was higher among males in the 18-25 year age group, but no BEST data partner reported a rate higher than 10 per 1 million person-days for this age group. Also, a meta-analysis of reports of myocarditis/pericarditis did not show higher risk among young male Moderna recipients than in those who received the Pfizer vaccine.
Peter Marks, director of FDA’s Center for Biologics Evaluation and Research (CBER), together with VRBPAC member Amanda Cohn, chief medical officer for the National Center for Immunizations and Respiratory Diseases at the CDC, clarified for the committee that a patient population specified in an EUA request can later only be narrowed, and not broadened, by ACIP. Cohn also serves as ACIP’s executive secretary.
ACIP is scheduled to meet on 21 and 22 October to discuss the topics addressed by this week’s VRBPAC meeting. The FDA usually follows the advice of its advisory committees, though it is not obligated to do so.
VRBPAC reconvenes on Friday to hear data supporting Johnson & Johnson’s request for an EUA for a booster for its vaccine; the committee will also review the evidence for “mix and match” booster regimens. Focus will be in (virtual) attendance.
VRBPAC briefing documents and livestream links


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