FDA Staff Find Few Faults with Pfizer-BioNTech COVID-19 Vax

The Pfizer-BioNTech mRNA COVID-19 vaccine candidate (BNT162b2) appeared to meet the criteria for an emergency use authorization, without FDA staff raising significant concerns in a briefing document released by the agency Tuesday.

In what will be arguably the most-watched Vaccine and Related Biological Products Advisory Committee (VRBPAC) meeting in history, members will decide on December 10 whether, based on the totality of scientific evidence, the vaccine “can be effective “to prevent COVID. -19 in people over 16 years of age, as well as whether the benefits outweigh the risks of the vaccine.

Overall, FDA technical staff expressed few concerns with the sponsors’ data. As previously reported in the first-line data, the efficacy of the vaccine 7 days after the second dose of vaccine was 95% (95% CI: 90.3% -97.6%) and was 66% (three cases in the control group; one in the vaccine group) versus severe cases. COVID-19 at least 7 days after the second dose, although with a non-significant and wide confidence interval (95% CI -124.8% to 96.3%) given the small number of events.

In October, the FDA noted that manufacturers needed “sufficient” cases of severe COVID-19, which could be fewer than five cases if the vaccine were effective enough.

Safety was comparable across all demographic groups. The FDA noted that the majority of adverse events were mild to moderate, with injection site reactions, fatigue, and headaches being the most common. Mild to moderate reactogenicity was reported more frequently in participants under 55 years of age.

These data come from Study C4591001, a randomized trial in which 75% of the participants (adults and adolescents later added to the ongoing study) were from the US They were randomized 1: 1 to receive two doses of the vaccine or placebo, 21 days apart.

The primary efficacy endpoint was the presence of a COVID-19 symptom, such as fever, new / increased cough, or new / increased shortness of breath, and a positive SARS-CoV-2 nucleic acid amplification test within the 4 days of the symptomatic period. Criteria for severe COVID-19 cases, a secondary endpoint, included respiratory failure, evidence of shock, and “clinical signs at rest indicative of severe systemic disease.”

This trial had about 42,000 participants. The mean age at vaccination was 50 years, men made up 51% of the participants, and 42% of the participants were 55 years or older. Approximately 80% of the participants were white and 10% were black. About a quarter reported being Hispanic or Latino and about 46% reported comorbidities, including about 35% with obesity.

Potentially vaccine-related adverse events were lymphadenopathy, or abnormally sized lymph nodes, where reports were ‘unbalanced’ in the vaccine versus placebo group (64 versus six). Four patients in the vaccine group reported Bell’s palsy versus zero in the placebo group.

While the FDA said there is “no clear basis on which to conclude a causal relationship at this time,” they would recommend surveillance for Bell’s palsy cases once the vaccine is applied to larger populations.

Appendicitis was the most common serious adverse event, with eight of the 12 cases occurring in the vaccine group, although the agency added that cases in the vaccine group “were not more frequent than expected in the general population. “. They also recommended that this be traceable after implementation.

As of November 14, approximately 51% of vaccine recipients in the safety population completed at least 2 months of follow-up after the second dose, and approximately 92% completed at least 1 month.

While the FDA noted that the overall median duration of follow-up was less than 2 months, because adolescents and HIV patients were added to the group, they concluded that data from the safety populations and from all enrollees “collectively provide a complete summary of safety. “

There were six deaths in the study (two in the vaccine group; four in the placebo). Deaths in the vaccine group were due to atherosclerosis, 3 days after the first dose and cardiac arrest. Two causes of death were unknown in the placebo group; two others were hemorrhagic stroke and myocardial infarction.

Although pregnancy was a reason for exclusion from the study, 23 pregnancies were reported as of November 14 (12 in the vaccine group; 11 with placebo). Two adverse events occurred in these pregnancies in the placebo group, including miscarriage.

The number of teens enrolled was too small to assess efficacy in participants younger than 16, the agency said. No data were available for participants aged 15 years or younger, and only one case was reported in adolescents aged 16 to 17 years, although they argued that it is “biologically reasonable” to extrapolate efficacy in this group from data from younger adults.

Besides adolescents, there was insufficient data on the safety of the vaccine among pregnant and lactating women and immunosuppressed people.

Thursday’s VRBPAC meeting will be webcast by the FDA as well as on YouTube and Twitter. The VRBPAC meeting in October attracted more than 15,000 views on YouTube.