FDA Provides Guidance for Vaccine Assessment Against COVID-19 Variants

The US Food and Drug Administration (FDA) has advised vaccine developers against conducting long-term, randomized control trials designed to evaluate vaccine candidates against emerging variants of the SARS-CoV-2 virus.

On Monday, FDA leadership including acting commissioner Janet Woodcock, MD, issued and gave statement around a new recommendation advising coronavirus 2019 (COVID-19) vaccines modified to respond to prominent virus variants be assessed through immunogenicity trials comparing immune responses of the modified vaccine against the targeted SARS-CoV-2 variant, with that of the prototype vaccine against its targeted virus.

Immunogenicity trials may be conducted in a single age group, with results extrapolated to other groups for which the prototype vaccine had already been authorized, as well as previously infected individuals in the same age groups.

Modified vaccines may be assessed for safety outcomes as simple as solicited local and systemic adverse events observed daily for ≥7 days after each study vaccination, as well as serious and other unsolicited adverse events during the immunogenicity study.

The update to this October 2020 guidance on Emergency Use Authorization (EUA) for COVID-19 vaccines—which includes testing and treatment guidance relative to variants—reflects currently available information suggesting vaccines already authorized by the FDA will remain effective against currently circulating SARS-CoV-2 strains.

“However, if there is an emergence of SARS-CoV-2 variant(s) in the US that are moderately or fully resistant to the antibody response elicited by the current generation of COVID-19 vaccines, it may be necessary to tailor the vaccines to the variant(s),” the FDA wrote.

Citing their experience in providing clinical guidance against new variants observed in previous epidemics including HIV and influenza, the FDA stressed that it had anticipated potential SARS-CoV-2 mutations which could alter prevention and mitigation strategies.

“While the FDA has already been communicating with individual medical product sponsors to provide information and scientific advice as they evaluate the impact of SARS-CoV-2 variants on their products, in the spirit of transparency and to continue to encourage public input on this important topic, the agency published this suite of guidances,” the FDA wrote.

Currently, just Pfizer-BioNTech’s BNT162b2 and Moderna’s mRNA-1273 are the lone COVID-19 vaccines granted EUA by the FDA. Both developers have stated in the last week intention to assess their two-dose mRNA vaccine’s product versus prominent variants based out of the UK and/or South Africa, or to at least seek out more information on clinical trial standards.

The updated vaccine trial guidance also comes 4 days prior to the scheduled Vaccines and Related Biologic Products Advisory Committee (VRBPAC) meeting for Johnson & Johnson’s single-dose adenovirus-based COVID-19 vaccine candidate. Pending assessment and discussion of submitted phase 3 data of the vaccine’s efficacy and safety in preventing COVID-19 in persons previously uninfected with the virus, the expert panel will weigh whether to recommend its authorization to the FDA.

Last month, the company shared preliminary data showing the vaccine was 85% effective in preventing severe COVID-19 disease in patients in regions including the US, Latin America, and South Africa, 28 days after vaccination.

Efficacy against severe disease increased over time, with no cases in vaccinated participants reported after day 49 in all adults 18 years and older. The vaccine's level of protection against moderate to severe COVID-19 infection was 72% in the US, 66% in Latin America, and 57% in South Africa.