麻豆传媒

The Pfizer-BioNTech mRNA COVID-19 vaccine candidate (BNT162b2) appeared to meet criteria for an emergency use authorization, with no major concerns raised by FDA staff in a released by the agency Tuesday.

In what will arguably be the most-watched Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting ever, members are set to decide Dec. 10 whether, based on the totality of scientific evidence, the vaccine "may be effective" in preventing COVID-19 in individuals ages 16 and older, as well as whether the benefits outweigh the risks of the vaccine.

Overall, the FDA's technical staff raised few concerns with the sponsors' data. As previously reported in topline data, vaccine efficacy 7 days after the second vaccine dose was 95% (95% CI 90.3%-97.6%), and was 66% (three cases in the control group; one in the vaccine group) against severe COVID-19 at least 7 days after the second dose, albeit with a wide and nonsignificant confidence interval (95% CI -124.8% to 96.3%) given the small number of events.

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

Safety was comparable across demographic groups. The FDA noted most adverse events were mild to moderate, with injection site reactions, fatigue, and headache as the most common. Mild-to-moderate reactogenicity was reported more frequently in participants younger than age 55.

This data came from study , a randomized trial in which 75% of the participants -- adults and adolescents who were later added to the ongoing study -- were from the U.S. They were randomized 1:1 to receive two doses of the vaccine or placebo, 21 days apart.

The primary efficacy endpoint was presence of one 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 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 illness."

This trial had about 42,000 participants. Mean age at vaccination was 50, men comprised 51% of participants, and 42% of participants were ages 55 and older. About 80% of participants were white and 10% were Black. About a quarter reported Hispanic or Latino ethnicity and about 46% reported comorbidities, including about 35% with obesity.

Adverse events potentially related to the vaccine were lymphadenopathy, or abnormal-sized lymph nodes, where reports were "imbalanced" in the vaccine versus placebo group (64 vs six). Bell's palsy was reported by four patients in the vaccine group versus zero in the placebo group.

While the FDA said "there is no clear basis upon which to conclude a causal relationship at this time," they would recommend surveillance for cases of Bell's palsy once the vaccine is deployed into larger populations.

Appendicitis was the most common serious adverse event, with eight of 12 cases occurring in the vaccine group, though the agency added cases in the vaccine group were "not more frequent than expected in the general population." They also recommended this could be tracked following deployment.

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

While the FDA noted the overall median duration of follow-up was less than 2 months, because adolescents and patients with HIV were added to the group, they concluded data from both the safety and all-enrolled populations "altogether provide a comprehensive summary of safety."

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

While pregnancy was grounds for study exclusion, 23 pregnancies were reported through Nov. 14 (12 in the vaccine group; 11 with placebo). Two adverse events occurred in these pregnancies in the placebo group, including spontaneous abortion.

The number of enrolled adolescents was too small to evaluate efficacy in participants younger than age 16, the agency said. No data was available for participants ages 15 and younger, and only one case was reported in adolescents ages 16-17, though they argued it is "biologically reasonable" to extrapolate efficacy in this group from the younger adult data.

In addition to adolescents, there were insufficient data about vaccine safety among pregnant and lactating women and immunocompromised individuals.

The VRBPAC meeting on Thursday will be webcast by the FDA, and also streamed on YouTube and Twitter. The VRBPAC meeting in October drew over 15,000 views on YouTube.

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