Biomarkers in Drug Development

MICHAEL R. BLEAVINS, PhD, is cofounder of MichiganTechnology and Research Institute. He retired fromPfizer/Warner-Lambert/Parke-Davis in 2006 and has twenty-threeyears of experience in pharmaceutical research, development, andbiomarkers with more than sixty-five peer-reviewed publications. CLAUDIO CARINI, MD, PhD, FRCPath, is Chief MedicalOfficer and Vice President for Clinical Research at Fresenius.Previously, Claudio served as Global Head of Translational Medicineat MDS and Global Head of Biomarkers at Hoffmann-La Roche. Claudiohas more than twenty years of experience in the field of immunologyand biomarkers and has authored more than 200 publications ininternational and domestic peer-reviewed journals. MALLE JURIMA-ROMET, PhD, is Senior Director forDevelopment and Regulatory Services at MDS Pharma Services, whereshe provides strategic and scientific consulting to pharmaceuticaland biotech sponsors, and leads drug development program teams.Malle has authored over forty peer-reviewed publications andis an adjunct professor at the University of Montreal. RAMIN RAHBARI, MS, is cofounder and Senior Consultant atInnovative Scientific Management. Previously, Ramin has heldpositions at Pfizer, Synaptic, and Parke-Davis pharmaceuticalcompanies, leading cross-functional biomarker teams.

Contributors. Preface. PART I BIOMARKERS AND THEIR ROLES IN DRUGDEVELOPMENT. 1 Biomarkers Are Not New (Ian Dews). 2 Biomarkers: Facing the Challenges at the Crossroads ofResearch and Health Care (Gregory J. Downing). 3 Enabling Go/No Go Decisions (J. Fred Pritchard andMalle Jurima-Romet). PART II IDENTIFYING NEW BIOMARKERS: TECHNOLOGYAPPROACHES. 4 Imaging as a Localized Biomarker: Opportunities and Challenges(Jonathan B. Moody, Philip S. Murphy, Edward P. Ficaro). 5 Protein Biomarker Discovery Using Mass Spectrometry-BasedProteomics (Joanna M. Hunter and Daniel Chelsky). 6 Quantitative Multiplexed Patterning of Immune-RelatedBiomarkers (Dominic Eisinger, Ralph McDade, and ThomasJoos). 7 Gene Expression Profiles as Preclinical and Clinical CancerBiomarkers of Prognosis, Drug Response, and Drug Toxicity (JasonA. Sprowl and Amadeo M. Parissenti). 8 Use of High-Throughput Proteomic Arrays for the Discovery ofDisease-Associated Molecules (Douglas M. Molina, W. John W.Morrow, and Xiaowu Liang). PART III CHARACTERIZATION AND VALIDATION. 9 Characterization and Validation Biomarkers in DrugDevelopment: Regulatory Perspective (Federico Goodsaid). 10 Fit-for-Purpose Method Validation and Assays for BiomarkerCharacterization to Support Drug Development (Jean W. Lee,Yuling Wu, and Jin Wang). 11 Molecular Biomarkers from a Diagnostic Perspective (KlausLindpaintner). 12 Strategies for the Co-Development of Drugs and Diagnostics:FDA Perspective on Diagnostics Regulation (Francis Kalush andSteven Gutman). 13 Importance of Statistics in the Qualification and Applicationof Biomarkers (Mary Zacour). PART IV BIOMARKERS IN DISCOVERY AND PRECLINICALSAFETY. 14 Qualification of Safety Biomarkers for Application to EarlyDrug Development (William B. Mattes and Frank D.Sistare). 15 Development of Serum Calcium and Phosphorus as ClinicalBiomarkers for Drug-Induced Systemic Mineralization: Case Studywith a MEK Inhibitor (Alan P. Brown). 16 Biomarkers for the Immunogenicity of Therapeutic Proteins andits Clinical Consequences (Claire Cornips and HuubShellekens). 17 New Markers of Kidney Injury (Sven A. Beushausen). PART V TRANSLATING FROM PRECLINICAL RESULTS TO CLINICAL ANDBACK. 18 Translational Medicine-A Paradigm Shift in Modern DrugDiscovery and Development: The Role of Biomarkers (Giora Z.Feuerstein, Salvatore Alesci, Frank L. Walsh, J. Lynn Rutkowski,and Robert R. Ruffolo, Jr.). 19 Clinical Validation and Biomarker Translation (David Lin,Andreas Scherer, Raymond Ng, Robert Balshaw, Shawna Flynn, PaulKeown, Rob McMaster, and Bruce McManus). 20 Predicting and Assessing an Inflammatory Disease and ItsComplications: Example from Rheumatoid Arthritis (ChristinaTrollmo and Lars Klareskog). 21 Pharmacokinetic and Pharmacodynamic Biomarker Correlations(J.F. Marier and Keith Gallicano). 22. Validating In Vitro Toxicity Biomarkers Against ClinicalEndpoints (Calvert Louden and Ruth A. Roberts). PART VI BIOMARKERS IN CLINICAL TRIALS. 23 Opportunities and Pitfalls Associated with Early Utilizationof Biomarkers: A Case Study in Anticoagulant Development (Kay A.Criswell). 24 Integrating Molecular Testing into Clinical Applications(Anthony A. Killeen). 25 Biomarkers for Lysosomal Storage Disorders (Ari Zimran,Candida Fratazzi, and Deborah Elstein). 26 The Value Chain in the Development of Biomarkers for DiseaseTargets (Charles W. Richard III, Arthur O. Tzianabos, WhaijenSoo). PART VII LESSONS LEARNED: PRACTICAL ASPECTS OF BIOMARKERIMPLEMENTATION. 27 Biomarkers in Pharmaceutical Development: The Essential Roleof Project Management and Teamwork (Lena King, Mall Jurima-Romet, and Nita Ichhpurani). 28 Integrating Academic Laboratories Into PharmaceuticalDevelopment (Peter A. Ward and Kent J. Johnson). 29 Funding Biomarker Research and Development Through the SmallBusiness Innovative Research Program (James Varani). 30 Novel and Traditional Nonclinical Biomarker Utilization inthe Estimation of Pharmaceutical Therapeutic Indices (Bruce D.Car, Brian Gemzik, and William R. Foster). 31 Anti-Unicorn Principle: Appropriate Biomarkers Don tNeed to be Rare or Hard to Find (Michael R. Bleavins and RaminRahbari). 32 Biomarker Patent Strategies: Opportunities and Risks(Cynthia M. Bott and Eric J. Baude). PART VIII WHERE ARE WE HEADING AND WHAT DO WE REALLYNEED? 33 IT Supporting Biomarker-Enabling Drug Development (MichaelHehenberger). 34 Redefining Disease and Pharmaceutical Targets ThroughMolecular Definitions and Personalized Medicine (Craig P. Webb,John F. Thompson and Bruce H. Littman). 35 Ethics of Biomarkers: The Borders of Investigative Research,Informed Consent, and Patient Protection (Heather Walmsley,Michael Burgess, Jacqui Brinkman, Richard Hegele, JanetWilson-McManus, and Bruce McManus). 36 Pathodynamics: Improving Biomarker Selection By Getting MoreInformation From Changes Over Time (Donald C. Trost). 37 Optimizing the Use of Biomarkers for Drug Development: AClinician's Perspective (Alberto Gimona). 38 Nanotechnology-Based Biomarker Detection (JoshuaReinke). Index.