Emergency Use Authorization (EUA) for an Unapproved Product Review Memorandum Identifying Information Application Type EUA (Event-driven EUA request) Application Number 27205 Sponsor Janssen Biotech, Inc. Submission Date February 4, 2021 Receipt Date February 4, 2021 Signatory Authority Marion F. Gruber, Ph.D., Director, CBER/OVRR Principal Discipline Reviewers Sudhakar Agnihothram, Ph.D., Committee chair, OVRR/DVRPA; from the Review Team Bharat Khurana, DVM, Ph.D., MBA, Regulatory Project Manager, OVRR/DVRPA; Rachel Zhang, M.D., Clinical reviewer, OVRR/DVRPA; Yosefa Hefter, M.D., Clinical reviewer, OVRR/DVRPA; Claudia Wrzesinski, Ph.D., Toxicology reviewer, OVRR/DVRPA; Ye Yang, Ph.D., Biostatistics reviewer, OBE/DB; Lei Huang, Ph.D., Biostatistics reviewer, OBE/DB; Marian Major, Ph.D., CMC/Product reviewer, OVRR/DVP; Alla Kachko, Ph.D., CMC/Product reviewer, OVRR/DVP; Pankaj (Pete) Amin, B.S., CMC/Facility reviewer; OCBQ/DMPQ; Holly Brevig, Ph.D., CMC/Facility reviewer; OCBQ/DMPQ; Jane Woo, M.D., Pharmacovigilance reviewer, OBE/DE; Brenda Baldwin, Ph.D., Data Integrity reviewer, OVRR/DVRPA; Haecin Chun, M.S., BIMO reviewer, OCBQ/DIS/BMB; Bhanu Kannan, M.S., BIMO reviewer, OCBQ/DIS/BMB; Oluchi Elekwachi, Pharm.D., MPH, Labeling reviewer, OCBQ/DCM/APLB Review Completion Date February 27, 2021 Established Name/Other names Janssen COVID-19 vaccine (Ad26.COV2.S) used during development Dosage Forms/Strengths and A 0.5 mL suspension administered as a single intramuscular Route of Administration injection at the dose level of 5×1010 virus particles (vp) Intended Use for EUA Active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Intended Population Individuals 18 years of age and older Janssen Ad26.COV2.S (COVID-19) Vaccine VRBPAC Briefing Document Table of Contents List of Tables ................................................................................................................................. 3 List of Figures ............................................................................................................................... 4 Glossary ........................................................................................................................................ 5 1. Executive Summary ................................................................................................................. 6 2. Background .............................................................................................................................. 8 2.1 SARS-CoV-2 Pandemic .................................................................................................... 8 2.2 Available Vaccines and Therapies for COVID-19 ............................................................. 9 2.3 EUA Request for the Janssen COVID-19 Vaccine ........................................................... 9 2.4 U.S. Requirements to Support Issuance of an EUA for a Biological Product ............................................................................................................................ 10 2.5 Applicable Guidance for Industry .................................................................................... 11 3. Janssen COVID-19 Vaccine .................................................................................................. 12 3.1 Vaccine Composition, Dosing Regimen .......................................................................... 12 3.2 Safety Experience of Ad26-based Vaccines ................................................................... 13 3.3 Proposed Use Under EUA .............................................................................................. 13 4. FDA Review of Clinical Safety and Effectiveness Data ......................................................... 13 4.1 Overview of Clinical Studies ............................................................................................ 13 4.2 Study 3001 ...................................................................................................................... 14 4.2.1 Design ..................................................................................................................... 14 4.2.2 Compliance with Good Clinical Practice ................................................................. 18 4.2.3 FDA Assessment of Phase 3 Follow-Up Duration .................................................. 18 4.2.4 Participant Disposition and Inclusion in Analysis Populations ................................ 19 4.2.5 Demographics and Other Baseline Characteristics ................................................ 20 4.2.6 Vaccine Efficacy ...................................................................................................... 25 4.2.7 Safety ...................................................................................................................... 39 5. FDA Review of Other Information Submitted in Support of the EUA ..................................... 54 5.1 Sponsor’s Plans for Continuing Blinded, Placebo-Controlled Follow-up ......................... 54 5.2 Pharmacovigilance Activities ........................................................................................... 55 5.3 Non-Clinical Studies ........................................................................................................ 56 5.4 Chemistry, Manufacturing, and Control (CMC) Information ............................................ 57 5.5 Clinical Assay Information ............................................................................................... 58 5.6 Inspections of Clinical Study Sites .................................................................................. 58 5.7 EUA Prescribing Information and Fact Sheets ................................................................ 59 6. Benefit/Risk Assessment in the Context of Proposed Indication and Use Under EUA .................................................................................................................................. 59 6.1 Known Benefits ............................................................................................................... 59 6.2 Unknown Benefits/Data Gaps ......................................................................................... 59 6.3 Known Risks ................................................................................................................... 61 6.4 Unknown Risks/Data Gaps ............................................................................................. 61 2 Janssen COVID-19 Vaccine Emergency Use Authorization Review Memorandum 7. VRBPAC Meeting Summary .................................................................................................. 62 8. Overall Summary and Recommendation ............................................................................... 63 9. References ............................................................................................................................ 65 10. Appendix A. Other Clinical Studies Ad26.COV2.S ................................................................ 67 11. Appendix B. Case Definitions for Mild COVID-19 and FDA Harmonized COVID-19 ................................................................................................................................... 69 List of Tables Table 1. Clinical Trials Submitted in Support of Efficacy and Safety Determinations of the Janssen COVID-19 Vaccine ............................................................................................... 13 Table 2. Analysis Populations ..................................................................................................... 17 Table 3. Participant Disposition by Age Group and Comorbidities, Full Analysis Set, Study 3001 .......................................................................................................................... 18 Table 4. Dispositiona, Efficacy Analysis Population, Study 3001 ................................................ 19 Table 5. Disposition, Safety Analysis Population, Study 3001 .................................................... 20 Table 6. Demographic Characteristics, Per-Protocol Set, Study 3001 ....................................... 21 Table 7. Demographic Characteristics, Full Analysis Set, Study 3001 ....................................... 22 Table 8. Participants With Comorbidities, Full Analysis Set, Study 3001 ................................... 23 Table 9. Demographic Characteristics, Safety Subset, Study 3001 ........................................... 24 Table 10. Vaccine Efficacy Against Centrally Confirmed Moderate to Severe/Critical COVID-19 With Onset at Least 14 and at Least 28 Days After Vaccination, Per- Protocol Set, Study 3001 .................................................................................................... 25 Table 11. Demographic Characteristics of Participants With Moderate to Severe/Critical COVID-19, Including Non-centrally Confirmed Cases, With Onset at Least 14 days After Vaccination, Per-Protocol Set .................................................................................... 26 Table 12. Vaccine Efficacy of First Occurrence of Moderate to Severe/Critical COVID-19, Including Non-centrally Confirmed Cases, With Onset at Least 14 or at Least 28 Days After Vaccination, by Demographic Characteristics, Per-Protocol Set, Study 3001 ........... 27 Table 13. Vaccine Efficacy of First