Pfizer-BioNTech COVID-19 Vaccine VRBPAC Briefing Document PFIZER-BIONTECH COVID-19 VACCINE (BNT162, PF-07302048) VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE BRIEFING DOCUMENT MEETING DATE: 10 December 2020 Page 1 090177e195a63925\Approved\Approved On: 30-Nov-2020 14:23 (GMT) Pfizer-BioNTech COVID-19 Vaccine VRBPAC Briefing Document TABLE OF CONTENTS LIST OF TABLES.....................................................................................................................3 LIST OF FIGURES ...................................................................................................................4 APPENDICES ...........................................................................................................................5 ABBREVIATIONS ...................................................................................................................6 EXECUTIVE SUMMARY .......................................................................................................8 1. BACKGROUND INFORMATION AND UNMET MEDICAL NEED ............................10 1.1. Regulatory Considerations ......................................................................................10 2. GENERAL PRODUCT INFORMATION ..........................................................................10 2.1. Coronavirus Spike Glycoprotein as Vaccine Target ...............................................11 2.2. RNA-Lipid Nanoparticle Formulation ....................................................................11 3. PROPOSED EUA INDICATION .......................................................................................12 4. SUMMARY OF KEY NONCLINICAL DATA .................................................................12 5. OVERVIEW OF CLINICAL STUDIES .............................................................................13 5.1. First-in-Human Phase 1/2 Study BNT162-01.........................................................14 5.2. Registration Phase 1/2/3 Study C4591001 ..............................................................14 5.2.1. Rationale for Vaccine Candidate and Dose Selection for Phase 2/3 Development....................................................................................................16 5.2.2. Continuation of Blinded Phase 3 Registration Study .................................16 5.2.3. Evaluation of Safety, Immunogenicity, and Efficacy in Study C4591001 .17 6. SUMMARY OF CLINICAL DATA ...................................................................................21 6.1. Study BNT162-01 Phase 1......................................................................................21 6.1.1. Demographics and Disposition in Study BNT162-01 Phase 1 ...................21 6.1.2. Immunogenicity in Study BNT162-01 Phase 1 ..........................................22 6.2. Study C4591001 Phase 1.........................................................................................25 6.2.1. Demographics and Disposition in Study C4591001 Phase 1 .....................25 6.2.2. Immunogenicity in Study C4591001 Phase 1 ............................................26 6.2.3. Safety in Study C4591001 Phase 1.............................................................27 6.3. Study C4591001 Phase 2/3 .....................................................................................30 6.3.1. Study Population in Study C4591001 Phase 2/3 ........................................30 6.3.2. Immunogenicity in Study C4591001 Phase 2 ............................................34 6.3.3. Safety in Study C4591001 Phase 2/3..........................................................35 6.3.4. Efficacy in Study C4591001 Phase 2/3 ......................................................53 Page 2 090177e195a63925\Approved\Approved On: 30-Nov-2020 14:23 (GMT) Pfizer-BioNTech COVID-19 Vaccine VRBPAC Briefing Document 7. PHARMACOVIGILANCE AND PHARMACOEPIDEMIOLOGY PLAN ......................72 8. RISK/BENEFIT ASSESSMENT ........................................................................................74 9. REFERENCES ....................................................................................................................75 LIST OF TABLES Table 1. Summary of Key Nonclinical Studies ......................................................12 Table 2. Summary of Clinical Studies ....................................................................13 Table 3. Follow-Up Time After Dose 2 – ~38000 Subjects for Phase 2/3 Analysis – Safety Population ....................................................................30 Table 4. Demographic Characteristics – ~38000 Subjects for Phase 2/3 Analysis – Safety Population ...................................................................................31 Table 5. Disposition of All Randomized Subjects – ~38000 Subjects for Phase 2/3 Analysis ..............................................................................................33 Table 6. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to 1 Month After Dose 2 – ~38000 Subjects for Phase 2/3 Analysis – Safety Population ....................................................................43 Table 7. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to Data Cutoff Date (14NOV2020) – Subjects With 2 Months Follow-Up Time After Dose 2 for Phase 2/3 Analysis – Safety Population .................................................................................................44 Table 8. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to Data Cutoff Date (14NOV2020) – Phase 2/3 (All Subjects) – Safety Population ......................................................................................46 Table 9. Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2 – Subjects Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population ...................................55 Table 10. Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2 – Subjects With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population .................56 Table 11. Vaccine Efficacy – First COVID-19 Occurrence After Dose 1 – Dose 1 All-Available Efficacy Population ...........................................................57 Table 12. Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Subgroup – Subjects Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population ..............59 Table 13. Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Risk Status – Subjects Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population..........61 Page 3 Pfizer-BioNTech COVID-19 Vaccine VRBPAC Briefing Document Table 14. Vaccine Efficacy – First COVID-19 Occurrence From 14 Days After Dose 2 – Subjects Without Evidence of Infection Prior to 14 Days After Dose 2 – Evaluable Efficacy (14 Days) Population........ ................63 Table 15. Vaccine Efficacy – First COVID-19 Occurrence From 14 Days After Dose 2 – Subjects With or Without Evidence of Infection Prior to 14 Days After Dose 2 – Evaluable Efficacy (14 Days) Population ...............64 Table 16. Vaccine Efficacy – First Severe COVID-19 Occurrence From 7 Days After Dose 2 – Subjects Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population......... .................65 Table 17. Vaccine Efficacy – First Severe COVID-19 Occurrence From 7 Days After Dose 2 – Subjects With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population ..............66 Table 18. Vaccine Efficacy – First Severe COVID-19 Occurrence After Dose 1 – Dose 1 All-Available Efficacy Population ...............................................67 Table 19. Vaccine Efficacy – First Severe COVID-19 Occurrence From 14 Days After Dose 2 – Subjects Without Evidence of Infection Prior to 14 Days After Dose 2 – Evaluable Efficacy (14 Days) Population ...............68 Table 20. Vaccine Efficacy – First Severe COVID-19 Occurrence From 14 Days After Dose 2 – Subjects With or Without Evidence of Infection Prior to 14 Days After Dose 2 – Evaluable Efficacy (14 Days) Population ..........69 Table 21. Vaccine Efficacy – First COVID-19 Occurrence Based on CDC- Defined Symptoms From 7 Days After Dose 2 – Subjects Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population ....................................................................70 Table 22. Vaccine Efficacy – First COVID-19 Occurrence Based on CDC- Defined Symptoms From 7 Days After Dose 2 – Subjects With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population ...................................................71 Table 23. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred Term – ~38000 Subjects for Phase 2/3 Analysis – Safety Population .................................................................................................87 LIST OF FIGURES Figure 1. Safety Evaluation Follow-Up Periods in Study C4591001 ......................18 Figure 2. Frequency and Magnitude of BNT162b2-induced CD4+ and CD8+ T Cell Responses ..........................................................................................22 Figure 3. S-Specific