Vaccines and Related Biological Products Advisory Committee Meeting February 26, 2021 FDA Briefing Document Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19 Sponsor: Janssen Biotech, Inc. 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 EUA Request for the Janssen Ad26.COV2.S Vaccine .....................................................8 2.3 U.S. Requirements to Support Issuance of an EUA for a Biological Product ............................................................................................................................9 2.4 Available Vaccines and Therapies for COVID-19 ............................................................9 2.5 Applicable Guidance for Industry ...................................................................................10 2.6 Safety and Effectiveness Information Needed to Support an EUA .................................10 2.7 Continuation of Clinical Trials Following Issuance of an EUA for a COVID-19 Vaccine ........................................................................................................11 2.8 Previous Meetings of the VRBPAC to Discuss Vaccines to Prevent COVID-19 ......................................................................................................................11 3. Topics for VRBPAC Discussion ...........................................................................................12 4. Janssen Ad26.COV2.S (COVID-19) Vaccine .......................................................................12 4.1 Vaccine Composition, Dosing Regimen .........................................................................12 4.2 Safety Experience of Ad26-based Vaccines ..................................................................13 4.3 Proposed Use Under EUA .............................................................................................13 5. FDA Review of Clinical Safety and Effectiveness Data ........................................................13 5.1 Overview of Clinical Studies ..........................................................................................13 5.2 Study 3001 ....................................................................................................................14 5.2.1 Design ...................................................................................................................14 5.2.2 FDA Assessment of Phase 3 Follow-Up Duration ..................................................17 5.2.3 Participant Disposition and Inclusion in Analysis Populations ................................18 5.2.4 Demographics and Other Baseline Characteristics ................................................20 5.2.5 Vaccine Efficacy ....................................................................................................25 5.2.6 Safety ....................................................................................................................39 6. Sponsor’s Plans for Continuing Blinded, Placebo-Controlled Follow-Up ..............................53 7. Pharmacovigilance Activities ................................................................................................54 8. Benefit/Risk Assessment in the Context of Proposed Indication and Use Under EUA ................................................................................................................................55 8.1 Known Benefits .............................................................................................................55 8.2 Unknown Benefits/Data Gaps........................................................................................56 8.3 Known Risks .................................................................................................................57 8.4 Unknown Risks/Data Gaps ............................................................................................58 2 Janssen Ad26.COV2.S (COVID-19) Vaccine VRBPAC Briefing Document 9. References ..........................................................................................................................59 10. Appendix A. Other Clinical Studies Ad26.COV2.S ...............................................................60 10.1 Study 1001 ..................................................................................................................60 10.2 Study 1002 ..................................................................................................................60 10.3 Study 2001 ..................................................................................................................60 10.4 Study 3009 ..................................................................................................................61 11. Appendix B. Case Definitions for Mild COVID-19 and FDA Harmonized COVID-19 .................................................................................................................................62 11.1 Case Definition for Mild COVID-19 ..............................................................................62 11.2 FDA Harmonized Case Definition for COVID-19 ..........................................................62 List of Tables Table 1. Clinical Trials Submitted in Support of Efficacy and Safety Determinations of the Janssen Ad26.COV2.S (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 .......................................20 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 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 Risk Factors for Severe COVID-19, Per-Protocol Set, Study 3001..................................................................................................................................29 Table 14. 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 Baseline SARS-CoV-2 Statusa, Full Analysis Set .............................30 Table 15. Vaccine Efficacy Against Centrally Confirmed COVID-19a With Onset at Least 14 or at Least 28 Days After Vaccination, Per-Protocol Set, Study 3001................................31 Table 16. Vaccine Efficacy Against Adjudicated Severe/Critical COVID-19 With Onset at Least 14 or at Least 28 Days After Vaccination, Per-Protocol Set, Study 3001 .................32 3 Janssen Ad26.COV2.S (COVID-19) Vaccine VRBPAC Briefing Document Table 17. Vaccine Efficacy of First Occurrence COVID-19 Requiring Medical Intervention Based on MRU, With Onset at Least 14 or at Least 28 Days After Vaccination, Per-Protocol Set, Study 3001 ............................................................................................33 Table 18. Vaccine Efficacy of First Occurrence COVID-19 Requiring Hospitalization,