Tuesday, December 08, 2020

Pfizer COVID-19 Vaccine Report Issued Today In Preparation For Emergency Authorization Meeting December 10

Summary of Pfizer COVID Vaccine Report Issued Today

Today Pfizer-BioNTech released it's long awaited report titled "Vaccines and Related Biological Products" intended for review by the FDA's Vaccines and Related Biological Products Advisory Committee's public meeting on December 10, 2020, as Pfizer has applied for emergency authorization for the Pfizer-BioNTech COVID-19 Vaccine.

The 53-page report is filled with detailed Tables and study specifics, and will not be easy reading for those mandated to study all those details and conclusions in order to quickly approve or not approve the vaccine for emergency use at this time. 

UPDATE: On Thursday, after 9 hours of presentation, discussions and questioning, the Advisory Committee voted 17 to 4 in favor of recommending to the FDA that the vaccine will provide more benefit than harm to release it for Emergency use by 16 year old and older. There was discussion of what will happen to the control group who originally were part of the vaccine trials for the last six months  haven twice taken a placebo vaccine, and the ramification if or when they will be offered the actual vaccine which will complicate or end the trial to compare the control group versus the group taking the actual vaccine, the trial which was scheduled to last for 24 months.

Errors In Report Found?

On page 20 (Table 4) it appears that there are numerical errors on the "Demographic Characteristics" of Participants, the number stated for age groups and the percentages stated in the Table do not appear to be correct as the totals combined for each age group don't agree with the totals as show as the top of the Table, making the percentages for each age group much lower than stated, and presumably incorrect. If incorrect, those numbers may possibly throw off statistics as reported in the other tables and final report conclusions.

Efficiency Claimed To Be 95% With Second Dose

In it's summary for the Advisory Committee meeting coming up Thursday it said, "In a mid-November analysis of 36,621 participants randomized 1 to 1 to vaccine or placebo who were included in the per-protocol efficacy analysis... efficacy in preventing confirmed COVID-19 occurring at least 7 days after the second dose of vaccine was 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group.

"Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across age groups, genders, racial and ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19. Secondary efficacy analyses suggested benefit of the vaccine in preventing severe COVID-19, in preventing COVID-19 following the first dose, and in preventing COVID-19 in individuals with prior SARS-CoV-2 infection, although available data for these outcomes did not allow for firm conclusions. 

"Safety data from approximately 38,000 participants greater than16 years of age randomized 1:1 to vaccine or placebo with a median of 2 months of follow up after the second dose suggest a favorable safety profile, with no specific safety concerns identified that would preclude issuance of an EUA. "

Adverse Reactions

"The most common solicited 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%), fever (14.2%); severe adverse reactions occurred in 0.0% to 4.6% of participants, were more frequent after Dose 2 than after Dose 1, and were generally less frequent in participants greater than 55 years of age (≤ 2.8%) as compared to younger participants (≤4.6%)."

The report says "Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile. From a safety perspective, a 2-month median follow-up following completion of the full vaccination regimen will allow identification of potential adverse events that were not apparent in the immediate postvaccination period. 

"Adverse events considered plausibly linked to vaccination generally start within 6 weeks of vaccine receipt. Therefore, a 2- month follow-up period may allow for identification of potential immune-mediated adverse events that began within 6 weeks of vaccination. From the perspective of vaccine efficacy, it is important to assess whether protection mediated by early responses has not started to wane. 

"A 2-month median follow-up is the shortest follow-up period to achieve some confidence that any protection against COVID-19 is likely to be more than short-lived. The EUA request should include a plan for active follow-up for safety (including deaths, hospitalizations, and other serious or clinically significant adverse events) among individuals administered the vaccine under an EUA in order to inform ongoing benefit-risk determinations to support continuation of the EUA."

Duration of protection of vaccine unknown

"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."

Vaccine effectiveness against asymptomatic infection unknown 

"Data are limited to assess the effect of the vaccine against asymptomatic infection as measured by detection of the virus and/or detection of antibodies against non-vaccine antigens that would indicate infection rather than an immune response induced by the vaccine. Additional evaluations will be needed to assess the effect of the vaccine in preventing asymptomatic infection, including data from clinical trials and from the vaccine’s use post-authorization." 

Vaccine effectiveness against long-term effects of COVID-19 disease 

"COVID-19 disease 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 (A pathological condition resulting from a prior disease, injury, or attack) of COVID-19 disease in individuals who are infected despite vaccination. 

"Demonstrated high efficacy against symptomatic COVID-19 should translate to overall prevention of COVID-19- related sequelae in vaccinated populations, though it is possible that asymptomatic infections may not be prevented as effectively as symptomatic infections and may be associated with sequelae that are either late-onset or undetected at the time of infection (e.g., myocarditis). 

"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 from the vaccine’s use postauthorization."

Other Safety Concerns To Be Monitored - Respiratory Disease, Pregnancy, Pediatric Concerns

Pfizer submitted a Pharmacovigilance Plan (PVP) to monitor safety concerns that could be associated with Pfizer-BioNTech COVID-19 Vaccine. "The Sponsor identified vaccine-associated enhanced disease including vaccine-associated enhanced respiratory disease as an important potential risk. Use in pregnancy and lactation and vaccine effectiveness are areas the Sponsor identified as missing information. In addition to the safety concerns specified by the Sponsor, FDA requested that the Sponsor update their PVP to include missing information in pediatric participants less than 16 years of age."

Vaccine effectiveness against transmission of SARS-CoV-2 Unknown 

Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination. 

"Additional evaluations including data from clinical trials and from 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." 

How the vaccine is administered

"The Pfizer-BioNTech COVID-19 Vaccine is supplied as a frozen [between -80°C to -60°C (- 112°F to -76°F)] multi-dose (5-dose) vial. The vaccine must be thawed and diluted in its original vial with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to administration. 

"After dilution, the vial contains 5 doses of 0.3 mL per dose. After dilution, the multiple-dose vials must be stored between 2°C to 25°C (35°F to 77°F) and used within 6 hours from the time of dilution. 

"The Pfizer-BioNTech COVID-19 Vaccine, BNT162b2 (30 μg), is administered intramuscularly (IM) as a series of two 30 μg doses (0.3 mL each) 21 days apart."

Pfizer's Full Report Available Here

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