Pfizer’s Covid-19 vaccine offers ‘some protection’ after first dose, FDA says it meets ‘success criteria’
The FDA had earlier indicated it would authorize a vaccine that is safe and at least 50% effective. The agency’s analysis shows that Pfizer's vaccine candidate appears to meet the safety requirements
Pfizer and its partner BioNTech’s coronavirus vaccine candidate has “met the prespecified success criteria,” according to a detailed analysis by the US Food and Drug Administration (FDA) before a crucial meeting of its vaccine advisory group. This sets the stage for an emergency authorization as early as this week.
On November 20, 2020, Pfizer and BioNTech submitted an emergency use authorization (EUA) request to FDA for its Covid-19 vaccine candidate, BNT162b2. The proposed dosing regimen is 2 doses, 30 µg each, administered 21 days apart. “The data submitted in this EUA request were consistent with the recommendations set forth in the FDA guidance on EUA for vaccines to Prevent COVID-19 and met the prespecified success criteria established in the protocol,” notes the agency.
The 53-page document reveals that Pfizer’s vaccine candidate offers “some protection” after the first dose itself. Data show the vaccine was at least 52.4% effective before the second dose. “Based on the number of cases accumulated after dose 1 and before dose 2, there does seem to be some protection against Covid-19 disease following one dose. However, these data do not provide information about longer-term protection beyond 21 days after a single dose. The efficacy observed after dose 1 and before dose 2, from a posthoc analysis, cannot support a conclusion on the efficacy of a single dose of the vaccine, because the time of observation is limited by the fact that most of the participants received a second dose after three weeks,” the scientists explain.
The agency says that two doses of the vaccine spaced three weeks apart were “highly effective” in preventing confirmed cases of Covid-19 at least seven days following the second dose. Overall, the vaccine was found to be 94.8% effective after the second dose, seven days of the inoculation.
The FDA had earlier indicated it would authorize a vaccine that is safe and at least 50% effective. The agency’s analysis shows that Pfizer's vaccine candidate appears to meet the safety and efficacy requirements necessary for EUA. According to the study, data “suggests a favorable safety profile, with no specific safety concerns identified that would preclude issuance” of EUA.
“The median duration of at least 2 months follow-up after completion of the 2-dose primary vaccination series meets the agency’s expectations in FDA’s guidance on its EUA for vaccines to prevent Covid-19. As such, FDA has determined that the sponsor has provided adequate information to ensure the vaccine’s quality and consistency for authorization of the product under EUA,” notes the FDA.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the FDA will meet on December 10 to discuss Pfizer’s EUA request. The committee will also discuss what additional studies should be conducted by the vaccine manufacturer following the issuance of the EUA to gather further data on the safety and effectiveness of this vaccine.
What does the report say?
Scientists found that the vaccine was effective in reducing the risk of confirmed severe disease after the first dose, an important finding as some health experts are concerned Covid-19 vaccines would protect against only mild to moderate disease. “The known benefits among recipients of the proposed vaccine relative to placebo are reduction in the risk of confirmed Covid-19 occurring at least 7 days after dose 2; reduction in the risk of confirmed Covid-19 after dose 1 and before dose 2; and reduction in the risk of confirmed severe Covid-19 any time after dose 1,” they explain.
There were 10 cases of severe illness in the trial, with nine of those in the placebo group. “The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe Covid-19 disease,” the findings state.
The most common adverse reactions were injection site reactions (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), and fever (14.2%). Severe adverse reactions were rare, most frequent after the second dose and generally less frequent in adults 55 years and older (2.8%), as compared to younger participants (4.6%). The FDA concludes that there were no “meaningful imbalances” in serious health complications or adverse events, between the two (vaccine and placebo) groups. “Available safety data from all participants enrolled was consistent with the safety profile for the approximately 38,000 participants with a median follow-up of 2 months,” write authors.
There were four cases of Bell’s palsy, temporary paralysis of facial muscles, in the group that received the vaccine, but reviewers did not suspect a link to the vaccine. A total of six deaths occurred in the reporting period: 2 deaths in the vaccine group and 4 in the placebo. All deaths represent events that occur in the general population of the age groups where they occurred, at a similar rate,” the study says.
The review found the efficacy of the vaccine was “uniformly high” across subgroups, except for participants identifying as multiracial and those who had been infected with the coronavirus before enrollment. It shows there were too few Covid-19 cases in those subgroups to interpret efficacy.
What is currently unknown?
Duration of protection: As the interim and final analyses have a limited length of follow-up, it is not possible to assess sustained efficacy over a period longer than 2 months, indicate authors.
Vaccine effectiveness against coronavirus transmission: The review stresses that data are limited to assess the effect of the vaccine against Covid-19 transmission from individuals who are infected despite vaccination. “Demonstrated high efficacy against symptomatic Covid-19 may translate to overall prevention of transmission in populations with high enough vaccine uptake, though it is possible that if efficacy against asymptomatic infection were lower than efficacy against symptomatic infection, asymptomatic cases in combination with reduced mask-wearing and social distancing could result in significant continued transmission,” it explains. According to researchers, additional evaluations, including data from clinical trials and vaccine use post-authorization, will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, in particular in individuals with asymptomatic infection.
Vaccine effectiveness against asymptomatic infection: Data is currently limited to assess the effect of the vaccine against asymptomatic infection. The FDA notes that additional evaluations will be needed to assess the effect of the vaccine in preventing asymptomatic infection, including data from clinical trials and the vaccine’s use post-authorization.
Effectiveness in individuals previously infected: According to experts, the primary endpoint was evaluated in individuals without prior evidence of coronavirus, and very few cases of confirmed Covid-19 occurred among participants with evidence of infection before vaccination. “Therefore, available data are insufficient to make conclusions about benefit in individuals with prior infection. However, available data, while limited, do suggest that previously infected individuals can be at risk of Covid-19 (that is, reinfection) and could benefit from vaccination,” they state.
Effectiveness against long-term effects of the disease: Covid-19 may have long-term effects on certain organs and at present, it is not possible to assess whether the vaccine will have an impact “on specific long-term sequelae of the disease in individuals who are infected despite vaccination.” Additional evaluations will be needed to assess the effect of the vaccine in preventing long-term effects of Covid-19, including data from clinical trials and the vaccine’s use post-authorization, recommends FDA.
Effectiveness in other groups: There is currently insufficient data to make conclusions about the safety of the vaccine in children under age 16, pregnant women and people with compromised immune systems.
Vaccine effectiveness against death: A larger number of individuals at high risk of Covid-19 and higher attack rates would be needed to confirm the efficacy of the vaccine against mortality, suggest experts. “However, non-Covid-19 vaccines (for example, influenza) that are efficacious against disease have also been shown to prevent disease-associated death. Benefits in preventing death should be evaluated in large observational studies following authorization,” conclude researchers.