Vaccines and Related Biological Products Advisory Committee Meeting Individuals using assistive technology may not be able to fully access the information contained in this file. For assistance, please send an e-mail to: [email protected] and include 508 Accommodation and the title of the document in the subject line of your e- mail. JANSSEN BIOTECH, INC. (A PHARMACEUTICAL COMPANY OF JOHNSON & JOHNSON) COVID-19 Vaccine Ad26.COV2.S VAC31518 (JNJ-78436735) SPONSOR BRIEFING DOCUMENT VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE MEETING DATE: 26 FEBRUARY 2021 Page 1 of 118 Janssen Biotech, Inc. COVID-19 Vaccine Ad26.COV2.S VRBPAC Briefing Document TABLE OF CONTENTS Table of Contents ........................................................................................................................2 List of Tables ..........................................................................................................................5 List of Figures .........................................................................................................................7 List of Abbreviations...................................................................................................................9 1 Executive Summary .......................................................................................................... 11 2 Background on COVID-19 ................................................................................................ 25 2.1 Overview of COVID-19 ............................................................................................ 25 2.2 Unmet Medical Need ................................................................................................. 25 2.3 Current Vaccine Options ............................................................................................ 26 3 Product Description, Platform Data and Candidate selection .............................................. 27 3.1 Product Description ................................................................................................... 27 3.1.1 AdVac® Platform ................................................................................................. 27 3.1.2 Mechanism of Action ........................................................................................... 28 3.1.3 Vaccine Candidate Selection ................................................................................ 29 3.2 Ad26.COV2.S Dose Selection Rationale .................................................................... 29 3.3 Proposed Emergency Use Authorization (EUA) Indication Statement ........................ 30 4 Supporting Nonclinical Investigations ............................................................................... 31 4.1 Nonclinical Immunogenicity and Efficacy ................................................................. 31 4.2 Nonclinical Safety ..................................................................................................... 31 4.2.1 Biodistribution ..................................................................................................... 31 4.2.2 Toxicology ........................................................................................................... 31 5 Regulatory and Clinical Development Overview ............................................................... 33 5.1 Regulatory Overview ................................................................................................. 33 5.2 Clinical Development Program: Initiated Studies ....................................................... 33 5.3 Clinical Development Program: Planned Studies ....................................................... 34 6 Clinical Immunogenicity ................................................................................................... 35 6.1 Assays Used for Immunogenicity Assessments .......................................................... 35 6.2 Phase 1/2a Study COV1001 ....................................................................................... 36 6.2.1 Study Design ....................................................................................................... 36 6.2.2 Humoral Immunogenicity .................................................................................... 37 6.2.3 Cellular Immunogenicity...................................................................................... 40 Page 2 of 118 Janssen Biotech, Inc. COVID-19 Vaccine Ad26.COV2.S VRBPAC Briefing Document 6.3 Phase 1 Study COV1002............................................................................................ 42 6.4 Phase 2a Study COV2001 .......................................................................................... 42 6.5 Phase 3 Study COV3001 Interim Immunogenicity Results ......................................... 43 7 Clinical Efficacy ................................................................................................................ 45 7.1 Phase 3 Study COV3001 (ENSEMBLE) – Single Dose Ad26.COV2.S...................... 46 7.1.1 Study Design ....................................................................................................... 46 Overall Design .............................................................................................. 46 Enrollment Criteria ....................................................................................... 47 Independent Review of Severe/Critical COVID-19 ....................................... 48 Endpoints ...................................................................................................... 48 Case Definitions ........................................................................................... 49 7.1.1.5.1 Case Definition for Moderate COVID-19 ................................................. 49 7.1.1.5.2 Case Definition for Severe/Critical COVID-19 ......................................... 50 7.1.1.5.3 Case Definition for Mild COVID-19 ......................................................... 51 7.1.1.5.4 US FDA Harmonized Case Definition for COVID-19 ............................... 51 7.1.1.5.5 Case Definition for Asymptomatic or Undetected COVID-19 ................... 51 Statistical Analyses ....................................................................................... 52 7.1.1.6.1 Sample Size Determination ....................................................................... 52 7.1.1.6.2 Analysis Populations ................................................................................ 52 7.1.1.6.3 Efficacy Analysis ...................................................................................... 53 7.1.2 Epidemiological Setting ....................................................................................... 54 7.1.3 Participant Disposition ......................................................................................... 55 7.1.4 Participant Demographics .................................................................................... 56 7.1.5 Primary Endpoint Results – Moderate and Severe Disease ................................... 58 Co-Primary Efficacy Results ......................................................................... 58 7.1.6 Secondary Endpoint Results ................................................................................. 61 Vaccine Efficacy Against Severe/Critical COVID-19 ................................... 61 Prevention of COVID-19 Requiring Medical Intervention ............................ 63 Prevention of COVID-19-Related Death ....................................................... 64 Vaccine Efficacy Against All Symptomatic COVID-19 (BOD) .................... 64 Vaccine Impact on Symptom Severity .......................................................... 64 Vaccine Impact on Asymptomatic COVID-19 Infections as Inferred Through Seroconversion .............................................................................................................. 66 Page 3 of 118 Janssen Biotech, Inc. COVID-19 Vaccine Ad26.COV2.S VRBPAC Briefing Document Effect of Vaccine on SARS-CoV-2 Viral Load ............................................. 66 Vaccine Efficacy Against US FDA Harmonized COVID-19 Definition ........ 66 7.1.7 Efficacy in Subgroups .......................................................................................... 67 Efficacy by Region/Country .......................................................................... 67 Efficacy by Demographic and Baseline Characteristics: Age, Sex, Race, Ethnicity, Comorbidities and Location ........................................................................... 67 Efficacy in HIV-Infected Participants ........................................................... 70 Efficacy in Regions with Newly Emerging SARS-CoV-2 Strains .................. 70 7.2 Proposed Amendment to Study Design for Placebo-controlled Studies with Ad26.COV2.S After Obtaining EUA ..................................................................................... 71 8 Clinical Safety and Reactogenicity .................................................................................... 73 8.1 Introduction and Methodology ................................................................................... 73 8.2 Safety Population ....................................................................................................... 74 8.3 Vaccine Exposure .....................................................................................................