With SARS-CoV-2 vaccine distribution and vaccination expected to be well underway in prioritized groups this month, data for the first of the vaccines revealed at an FDA panel meeting show that benefits from the Pfizer and BioNTech vaccine begin early. Trial data show that efficacy is maintained for more than 79 days after completing the two-shot regimen.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) met on Dec. 10 to discuss the Pfizer data and voted 17-4 (with one abstention) that the evidence supported an EUA in those 16 and older. Once granted, the EUA marks the beginning of a new phase of the pandemic, with new challenges and also new reasons for hope that the crisis will begin to ebb next year. Vaccines are slowly rolling out across the globe, with the UK authorizing the Pfizer vaccine on Dec. 2, followed by Canada on Dec. 9.
Pfizer had reported that the vaccine efficacy was 95% seven days after the second dose, meaning that 95% fewer individuals in the vaccine group had symptomatic COVID-19 than in the placebo group. Pfizer’s vaccine is delivered in two intramuscular injections administered 21 days apart.
According to FDA briefing materials published on Dec. 8, efficacy can be detected starting about 14 days after the first dose, with early efficacy of 52% between the first and second dose. Efficacy reaches 95% at day 28, seven days after the second dose.
Pfizer is not proposing a one-dose regimen and the FDA cautioned against reading too much into the single-shot results between the first and second doses. “These data do not provide information about longer term protection beyond 21 days,” the agency concluded. The pivotal trial supporting Pfizer and BioNTech’s EUA application did not have a single-dose arm.
The FDA panel meeting also offered the first look at the breakdown in efficacy and safety by groups most at risk for severe adverse outcomes from COVID-19, including minorities, older individuals and those with comorbid conditions.
Overall, the efficacy was similar across age groups (95.6% in people 16 to 55 years old; 93.7% in those over 55). When the data were parsed by age and risk of severe outcomes due to comorbid conditions, the efficacy differed slightly, though the sample sizes were smaller. For example, the efficacy was 100% in those over 65 who were not at risk compared with 92% for those in the same age group but at risk.
Across racial demographics for which there were at least 1,000 participants in each arm, the efficacy was similar to the 95% seen in the broader population. However, the number of participants and cases in some of the racial subgroups “limits the interpretability of the [vaccine efficacy] results,” the FDA said.
The FDA concluded that the safety profile “did not raise specific safety concerns.” Pain at the injection site was the most common reaction (83.1% first shot; 78% second shot) followed by redness (4.5%; 5.9%) and swelling (5.8%; 6.3%) in participants 18-55 years of age. Pain reports were lower in those over 55 while rates of redness and swelling were similar after the first dose but slightly higher than the younger cohort after the second dose (7.2% and 7.5%, respectively).
Systemic events were greater after the second dose, which could allay some concerns that individuals will not return for the second dose because of tolerability, including fever (2.7% for the first dose; 13.6% for the second), fatigue (41.5%; 55.5%), headache (34.5%; 46.1%) and chills (10.6%; 29.6%).
While the company did include individuals down to age 12 in the pivotal Phase II/III trial, Pfizer requested authorization for those 16 and older because it had only recently expanded recruitment to younger people and didn’t yet have enough data to support a benefit-risk analysis in that population.
Pfizer’s vaccine uses messenger RNA (mRNA) to encode harmless segments of a key part of the SARS-CoV-2 virus. Upon injection, the mRNA is delivered to cells that then use the mRNA as a blueprint to make the virus’ protein segments. Once the body senses these virus proteins, it mounts an immune response against them. This process prepares the body’s immune system should it encounter the SARS-CoV-2 virus. The technology is still relatively new, but the high rate of efficacy at preventing symptomatic COVID-19 cases could translate into greater use of the technology in the future.
As the first vaccines start to roll out to vaccination centers in the US, attention is turning to supply logistics as well as how companies such as Pfizer will be able to assess the long-term safety and efficacy of the vaccine once it becomes available to the broader population.
The CDC’s Advisory Committee on Immunization Practices (ACIP) said that healthcare workers and residents of long-term care facilities should be first in line for the vaccines, and the leaders of Operation Warp Speed have said they expect Pfizer will be able to supply 20 million doses of its vaccine this month, enough to fully vaccinate 10 million Americans. The US has a contract for up to 100 million doses from Pfizer.
Moderna Therapeutics is expected to supply a similar number of doses to the US for its COVID-19 vaccine, which will be reviewed by the FDA VRBPAC on Dec. 17 and likely available just days after. HHS Secretary Alex Azar said on Dec. 2 that the US is “on track to be able to ship enough vaccine for 20 million Americans before the end of the year.”
One question to be answered as vaccines are authorized is how to handle individuals in the placebo group. The concern is that placebo participants who are in the prioritized groups for vaccination would ethically have to be unblinded (that is, told they were given placebo) and then may drop out of the trial to receive the vaccine.
The FDA has requested that companies include strategies in EUA applications about how to maintain the blind in their Phase III trials. In its briefing materials, Pfizer said that it may permit the placebo patients to cross over to the treatment arm and receive the vaccine, which would keep them enrolled in the trial to monitor safety and efficacy. “Safety follow up of actively vaccinated participants, including monitoring for COVID-19 cases, will provide ongoing information on continuing effectiveness, even in the absence of a placebo group, particularly by reference to local COVID-19 rates,” the company said.