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FDA Briefing Document Dermatologic and Ophthalmic Drugs Advisory FDA Briefing Document Dermatologic and Ophthalmic Drugs Advisory Committee Meeting July 19, 2016 Background Package for BLA 761032 Siliq (brodalumab) injection, 210 mg/1.5 ml FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF NEW DRUGS DIVISION OF DERMATOLOGY AND DENTAL PRODUCTS DISCLAIMER STATEMENT The attached package contains background information prepared by the Food and Drug Administration (FDA) for the panel members of the advisory committee. The FDA background package often contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. We have brought Siliq (brodalumab) injection, 210 mg/1.5 ml to this Advisory Committee in order to gain the Committee’s insights and opinions. The background package may not include all issues relevant to the final regulatory recommendation, but instead is intended to focus on issues identified by the Agency for discussion by the advisory committee. The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized. The final determination may be affected by issues not discussed at the advisory committee meeting. Table of Contents Division Director Memorandum ..................................................................................................... 5 I. INTRODUCTION ................................................................................................................... 7 II. SUMMARY OF EFFICACY ................................................................................................ 15 A. Clinical Trial Data ................................................................................................................. 15 B. Efficacy Across Biologics for Psoriasis ................................................................................ 16 III. SUMMARY OF SAFETY .................................................................................................... 17 A. Clinical Trial Data ................................................................................................................. 17 1. Deaths ................................................................................................................................ 17 a. Suicide Ideation and Behavior (SIB) ................................................................................. 18 i. Introduction to SIB ......................................................................................................... 18 ii. Division of Biometrics 7 (DB7) Analysis of SIB ....................................................... 19 iii. Division of Pharmacovigilance (DPV) Review of SIB and other Neuropsychiatric Events .................................................................................................................................... 26 iv. Division of Epidemiology (DEPI) Review of SIB ..................................................... 32 v. DPP Conclusions and Recommendations for SIB ...................................................... 36 b. Major Adverse Cardiovascular Events (MACE) ............................................................... 37 i. Introduction to MACE ................................................................................................... 37 ii. DB7 Analysis of MACE ............................................................................................. 37 iii. DEPI Review of MACE ............................................................................................. 41 iv. Division of Cardiorenal Products (DCRP) Review of MACE ................................... 43 2. Serious Adverse Events (SAEs)......................................................................................... 44 3. Common Adverse Events .................................................................................................. 46 4. Events of Special Interest................................................................................................... 46 a. Neutropenia ........................................................................................................................ 47 b. Infections and Infestations ................................................................................................. 48 c. Crohns’ Disease ................................................................................................................. 51 B. Clinical Pharmacology .......................................................................................................... 52 1. Pharmacokinetics (PK) of brodalumab in subjects with psoriasis ..................................... 52 2. Pharmacodynamics and potential role of IL-17A in suicidal ideation behavior (SIB) ...... 52 C. Risk Management .................................................................................................................. 55 1. Risk Management Options for Suicidal Ideation and Behavior (SIB) Observed in Clinical Trials with Brodalumab ............................................................................................................ 55 a. Introduction ........................................................................................................................ 55 b. Background ........................................................................................................................ 56 i. Product Information ........................................................................................................ 56 ii. Risk Evaluation and Mitigation Strategies ................................................................. 56 c. Benefit and Risk Considerations for brodalumab .............................................................. 57 i. Summary of the brodalumab Clinical Development Program ....................................... 57 ii. Key Findings of brodalumab Efficacy Results ........................................................... 58 iii. Serious Risk of suicidal ideation and behavior (SIB) Seen with brodalumab............ 58 iv. Risk Management Strategies Used in Clinical Trials ................................................. 58 d. Risk Management Proposed by the Product Sponsor ........................................................ 59 i. Product Sponsor Proposed Labeling .............................................................................. 59 ii. Product Sponsor Proposed REMS .............................................................................. 60 e. DRISK Risk Management Considerations for brodalumab............................................... 60 i. The Seriousness of Any Known or Potential Adverse Events Related to the Drug and Background Incidence of Such Events in the Population Likely to Use the Drug ............... 61 ii. The Size of the Population Likely to Use the Drug .................................................... 61 iii. The Seriousness of the Disease or Condition ............................................................. 62 iv. The Expected Benefit of the Drug .............................................................................. 62 v. The Expected or Actual Duration of Treatment ......................................................... 62 vi. Whether the Drug is a New Molecular Entity ............................................................ 62 vii. Additional Risk Management Considerations for brodalumab .................................. 63 f. Risk Management Options for SIB Observed with brodalumab ....................................... 63 i. Labeling .......................................................................................................................... 63 ii. Communication Plan .................................................................................................. 64 iii. Elements to Assure Safe Use (ETASU) ..................................................................... 64 2. Discussion .......................................................................................................................... 66 3. Summary ............................................................................................................................ 67 IV. PRELIMINARY TOPICS FOR THE ADVISORY COMMITTEE ..................................... 68 APPENDICES .............................................................................................................................. 69 Division of Psychiatry Products Review .................................................................................. 69 Division of Cardiorenal Products (DCRP) Review of MACE ................................................. 76 Division Director Memorandum Department of Health and Human Services Public Health Service Food and Drug Administration Center for Drug Evaluation and Research Office of Drug Evaluation III Division of Dermatology and Dental Products M E M O R A N D U M Date: June 22, 2016 From: Kendall A. Marcus, MD Director, Division of Dermatology and Dental Products Office of Drug Evaluation III, CDER, FDA To: Chair, Members and Invited Guests Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) Subject: Overview of the July 19, 2016 DODAC meeting Siliq (brodalumab) injection, 210 mg/1.5 ml for the treatment of adults with chronic
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