FDA biomarker qualification program Paul Hockings, Imaging Director - PowerPoint PPT Presentation

FDA biomarker qualification program Paul Hockings, Imaging Director Antaros Medical - An externalized R&D function - Design and Delivery of Decision enabling studies in cardiometabolic drug development

Objectives • Overview of regulatory framework for biomarkers • Concept of Use • Next steps

Guidelines for prevention of CKD The primary efficacy endpoint should be the prevention or slowing of decline in the level of renal function, defined as “Clinically meaningful and stable GFR loss rate” with or without: • Prevention of proteinuria/albuminuria or • Time to occurrence of CKD 3 or • Incidence rate of CKD 3 or higher NKF workshop March 15-16 on validation of novel surrogate endpoints in early CKD

Biomarkers in Drug Development /Clinical Practice Biomarkers in Drug Biomarkers as a diagnostic Development tool Objective: Establish EMA/US EMA/US the biomarker for use in multiple development programs Biomarker Qualification Acceptance through stand alone studies Letter of intent Acceptance through Drug Approval US Responsible : Generally Consortia EU Responsible: Anybody Responsible parties : Anybody FDA Process : CDRH process – 90 days/PMA 120 days FDA/EMA EU notified body : Devices except FDA Responsible parties : Sponsors EMA IVD • Review Team: BQRT FDA Process : Review division Day -60 : letter of intent IVDs self registration • Consultation and advice EMA Process: Discuss CHMP • Public consultation • Review and comments working party Day 190 : CHMP • Approval adoption • Public comments Biomarker Information Biomarker Information Biomarker Information Stand alone IFU Embedded in drug labels Qualified biomarkers announced E.g.: Troponin E.g.: Immune cancer therapy as draft guidance

Concept of Use Diagnostic/Enrichment e.g. fast progressors Diagnostic/Prognostic e.g. hyperfilterers Drug Development Tool Patient Selection Understanding disease biology/treatment action Use of a prognostic biomarker Exploratory Biomarker Patient Stratification Acceleration of development timelines Pharmacodynamic Biomarker Surrogate Endpoint Repeat Measurements Monitoring A biomarker to evaluate Drug safety/mode of action Assessment of drug/target engagement Drug Metabolism Target Engagement

FDA 21st Century Cures Act • 21st Century Cures Act enacted December 2016 • Qualification of Drug Development Tools (DDT) was added • Formally establishes an updated, multi-step process for DDT qualification • Qualification of a DDT is for a specific context of use (COU) • The qualification process includes three submissions: • Letter of Intent (LOI) • Qualification Plan (QP) • Full Qualification Package (FQP)

Initial FDA interaction - Critical Path Innovation Meeting To receive early indication of regulatory feasibility National Kidney Foundation FDA: PARENCHIMA Consortium Biomarker Qualification Program • Deputy Director FDA: DCaRP* • Deputy Director Critical Path Institute • Medical division lead • Director • Medical Reviewer FDA: In Vitro Diagnostics and Radiological Health • Biomarker engineer • Need of alignment between consortiums and diagnostic companies • Concept of Use is key for the LOI process * Division of Cardiovascular and Renal Products (DCaRP)

Qualification of Biomarker and/or Diagnostic tool Qualification of Biomarker • Craft letter of intent – one letter to both FDA and EMA • Information included • Proposed Context of Use (COU) (limited to 500 characters) • Describe PARENCHIMA program – emphasizing current knowledge EMA will give feedback first time 90 days after submission • 150 days after submission we will be asked to come back with clinical evidence and get recommendations • After supplying data we might have approval after an additional 100 days FDA no specific timelines • 2-4 months after submission we will be asked for briefing document or suggested to go to CPIM Diagnostic tool • DeNovo 510 K – define Pro/Con – Timing • CE marking – define Pro/Con – Timing

EMA Procedures for Qualification of Biomarker Abbreviations: QT : Qualification team SAWP : Scientific advice working party CHMP : Committee for Medicinal Products for Human Use Qualification of novel methodologies for drug development: guidance to applicants EMA/CHMP/SAWP/72894/2008

FDA Biomarker Qualification Process Note: The timeline based on our experience to date and may vary. This timeline does not capture the time needed by submitters to generate the data and submit the necessary documents (Letter of Intent (LOI), Briefing document, and Final Qualification Package) or requested additional information. Amur et al, Clin. Pharm. Ther. 98 (1) 34-46, 2015

Conclusion • Need to decide Diagnostic Tool vs Drug Development Tool • Need to decide Concept of Use • FDA, EMA or both • Need to establish links to the National Kidney Foundation and other advisory bodies • Method qualification is stronger if broad • many sites, many countries can replicate findings • deliver data with multiple different drugs • open platforms create better penetration • Big Pharma have Regulatory Departments with expertise in interactions with authorities

Questions?