Pfizer/BioNTech COVID-19 vaccine efficacy: Six key questions

The Pfizer/BioNTech announcement today on findings from their first interim analysis of its Phase 3 COVID-19 vaccine candidate study showing 90% efficacy among 94 cases included the following excerpts, with key data pending:

• “Submission for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) planned for soon after the required safety milestone is achieved, which is currently expected to occur in the third week of November.”
• “After discussion with the FDA, the companies recently elected to drop the 32-case interim analysis and conduct the first interim analysis at a minimum of 62 cases. Upon the conclusion of those discussions, the evaluable case count reached 94 and the DMC performed its first analysis on all cases. The case split between vaccinated individuals and those who received the placebo indicates a vaccine efficacy rate above 90%, at 7 days after the second dose. This means that protection is achieved 28 days after the initiation of the vaccination, which consists of a 2-dose schedule”.
• “The Phase 3 clinical trial of BNT162b2 began on July 27 and has enrolled 43,538 participants to date, 38,955 of whom have received a second dose of the vaccine candidate as of November 8, 2020. Approximately 42% of global participants and 30% of U.S. participants have racially and ethnically diverse backgrounds. The trial is continuing to enroll and is expected to continue through the final analysis when a total of 164 confirmed COVID-19 cases have accrued.”
• “The study also will evaluate the potential for the vaccine candidate to provide protection against COVID-19 in those who have had prior exposure to SARS-CoV-2, as well as vaccine prevention against severe COVID-19 disease.”
• “In addition to the primary efficacy endpoints evaluating confirmed COVID-19 cases accruing from 7 days after the second dose, the final analysis now will include, with the approval of the FDA, new secondary endpoints evaluating efficacy based on cases accruing 14 days after the second dose as well.”

This is encouraging news today by press release. Six key data questions are still pending in details. They will very likely be addressed when the request for FDA EUA is submitted later this month:

1. What is the detailed safety profile and specific adverse event profile?
2. What was the spectrum of clinical disease in the placebo group infected by the virus?
3. How many severe cases of COVID-19 were in the placebo group? (The FDA has stated at least 5 cases of severe disease are needed to help evaluate for Enhanced Respiratory Disease (ERD) in vaccine recipients).
4. What was the spectrum of clinical disease in the vaccine group infected by the virus?
5. Were there any severe cases (or any evidence of vaccine-associated enhanced respiratory disease (ERD) in the small number of persons infected after receiving the vaccine?
6. What impact did the vaccine have on transmission of the virus?