Fast Track Drug Development The Clinical (Caleidoscopic) Perspective

Transcription

1 20 Years AGAH, Annual Meeting, Hamburg February 2010 Fast Track Drug Development The Clinical (Caleidoscopic) Perspective Fritz R. Bühler, MD ECPM, University of Basel European Innovative Medicine Initiative, PharmaTrain, Coordinator ex Roche Head Global Clinical Research and Development February 2010 / 1

2 Stakeholders Individual, Patient-specific Decision Patient Physician Drug- and Populationspecific Decisions Health Care Provider Regulator Industry (Academic) Researcher February 2010 / 2

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4 Pharma needs to alter the blockbuster approach Because Serendipitous discovery of one size fits all drugs is increasingly difficult and costly Scientific advances in biology, IT, mobile and networking technologies offer radically new approaches Health technology assessment is now part of health care decision making Patients and patient groups have growing influence and demand greater access to treatments Industry must deliver higher value medicines to patients and demonstrate clear benefits February 2010 / 4 Training Platform

5 Significant new Technologies emerged Protein chips Transgenic animals Proteomics In silico experimentation Pharmacogenomics Bioinformatics Cheminformatics Source: Strategic Planning Pharma Molecular modelling Functional genomics February 2010 / 5

6 which will trigger a paradigm shift in R&D and medicine From To Clinical definition of disease diagnosis Molecular definition diagnosis and predisposition Courtesy of Don Stanski, Novartis February 2010 / 6

7 New Technologies Understanding of disease at molecular level Better drug targets Preventive medicine Identification of drugs Diagnostics Knowledge of individual risk profiles Drug therapy will become more selective Gene therapy partly replacing existing therapies February 2010 / 7

8 Frontloaded High Throughput Drug Development Target validation HTS CCS POC EIM FDP NDA Approval Hit Market Lead Identification Optimization 00 0 I II III IIIB IV Combinatoral chemistry Genomics Proteomics February 2010 / 8 SAR HTS (Cell) Assays Mech ADME Tox Interactions Bioinformatics CLOP Exploratory clinical research Simulation Modeling Techniques Genome-based subject selection

9 Frontloaded High Throughput Drug Development Genomics-based (GB) Pathophysio (PP)-logical Whole body pharmacokinetic (PK) Toxicokinetic (TK) and Pharmacodynamic (PD) model February 2010 / 9

10 Key Drivers to Transform Development Modeling and simulation Rapid compound selection in man Biomarkers Innovative clinical trial design Innovative approaches to initial registration ( provisional approval ) Integrated safety assessment & risk management Quality by design manufacturing February 2010 / 10

11 Modeling and Simulation is fundamental to a new Paradigm of Drug Develoment Modeling & Simulation Build the model Market Access Confirm the model Provisional Approval Monitored Release Full Approval Full Release Biomarkers l continuous sharing of data with Health Authority l February 2010 / 11

12 Biomarkers A simple conceptual architecture Biomarkers Pharmacodiagnostic Biomarkers Treatment eligibility Response prediction Pharmacological Biomarkers Pharmacodynamic markers Pharmacokinetic markers Mechanism of action markers Disease Biomarkers Predisposition Early detection Prognosis Monitoring/ Recurrence February 2010 / 12

13 Disease Subset Definition Many currently defined diseases are clinical syndromes (defined observationally) undoubtedly comprised of a collection of distinct pathogenic states New genomic, proteomic, imaging, etc. biomarkers may provide better discrimination by providing more information on underlying pathologic pro-cesses (without necessarily providing full mecha-nistic, explanatory data) February 2010 / 13

14 Learn-Confirm Paradigm Framework for Optimal Drug Development Lewis B. Sheiner, M.D., Ph.D. Physician and Scientist Learning mechanistic (causal) understanding of product exposure response relationships LEARNING CONFIRMING Confirming demonstrating evidence of mechanism, therapeutic concept, safety & effectiveness February 2010 / 14

15 Frontloaded High Throughput Drug Development Target validation HTS CCS POC EIM FDP NDA Approval Hit Market Lead Identification Optimization 00 0 I II III IIIB IV Combinatoral chemistry Genomics Proteomics February 2010 / 15 SAR HTS (Cell) Assays Mech ADME Tox Interactions Bioinformatics CLOP Exploratory clinical research Simulation Modeling Techniques Genome-based subject selection

16 How will the R&D process look in 2020? Today Intensive all-or-nothing regulation Discovery & screening Developing leads Pre-clinical evaluation Phase I Phase II Phase III Submission MAA / NDA Phase IIIb / IV Scientific advice / pre-ind Submission of CTA / IND CIM CIS Launch 2020 Collaborative, evolving, automated regulation Instant automated Patho approvals Physiology CIM = Confidence in mechanism CIS = Confidence in safety IND = Investigative New Drug CTA = Clinical Trial Application MAA = Marketing Authorisation Application CIM Discussion and agreed plan of action with Regulators Courtesy of Steven Arlington, PWC Automated In-life Molecule submission/ licensing Development approvals trials CIS Limited launch with Living Licence Development loop for extended indications and regulatory activities February 2010 / 16

17 How will the R&D process look in 2020? Patho Physiology Instant automated approvals CIM Discussion and agreed plan of action with Regulators Disease knowledge Public domain knowledge Automated In-life Molecule submission/ licensing Development approvals trials CIS Limited launch with Living Licence Contextual Testable Pathophysiology hypotheses Internal understanding Development loop for extended indications and regulatory activities CIM = Confidence in mechanism CIS = Confidence in safety Early human IND = Investigative New Drug Studies (POC) CTA = Clinical Trial Application MAA = Marketing Authorisation Application February 2010 / 17 Biology Epidemiology omics Etc. Disease subtype Mechanisms Targets Biomarkers Safety Incidence Economics Differentiation Targets Molecular entities Patient sub-type Disease specific biomarkers Efficacy biomarkers Safety biomarkers Differentiation

18 How will the R&D process look in 2020? Patho Physiology Instant automated approvals CIM Discussion and agreed plan of action with Regulators Automated In-life Molecule submission/ licensing Development approvals trials CIS Limited launch with Living Licence Pharm Sci, Biomarkers External understanding Devices Development loop for extended indications and regulatory activities CIM = Confidence in mechanism CIS = Confidence in safety IND = Investigative New Drug CTA = Clinical Trial Application MAA = Marketing Authorisation Application Regulatory Toxicology Efficacy & Safety Clinical trials Submission Preparation Biomarker, Device, live licence February 2010 / 18

19 February 2010 / 19 PharmaTrain

20 Four Education and Training Excellence Programmes: European Medicines Research Training Network EMTrain European Modular Education and Training Progarmme in Safety Sciences for Medicine Safe SciMET Pharmaceutical Medicine Training Programme PharmaTrain European progarmme of Pahrmacovigilance and Pharmacoepidemiology Eu2P February 2010 / 20 PharmaTrain

21 Postgraduate Three Tier Modular Process: Good Bologna Practice, GBP Diploma Exam MDDS/MSc Concept Syllabus-based Learning outcomes Base Course / Master extension Modularity ECTS/modul (1+3+1) Mobility Base- Courses Extension Modules Work-Project Thesis (10 ECTS) Electives (Research) Project Learning Paths mono-centric, 20% e-blended multi-centric, 50% e-blended distant, 80% e-blended CPD Lifelong learning Workload 60 ECTS à 30 hrs = 1800 hrs = 1 academic year February 2010 / ECTS Knowledge 60 ECTS Expertise 90 ECTS Competence

22 MDDS-Example Disease-Biology- Based Pharmacology Medicinal Chemistry - Base Course Modules (circle) - MDDS mandatory Extension Modules (elipse) - Elective Modules (stippled) Global Drug Development and Pharmaceutical Business Environment Pharmacology ADME, PK/PD Pharmaceutical Technologies From Preclinical Testing to Proof of Concept in Humans Learning and Confirming Trials: Finding and Confirrming the Right Dose Drug Safety / Surveillance CMC/GMP Master Thesis Confirming Trials: Methodology and Biostatistics The Global Registration and Market Approval Process Practice of Clinical Trials & Regulation European Course for Biobusiness Development Integrated Product Development, Portfolio Management and Marketing Pharmacoepidemiology Principles of Marketing Management Ethical Issues in Biomedical Research European Course for Life Sciences Exe.Leadership Few examples of the PharmaTrain (IMI E+T?) Electives Platform February 2010 / 22