One of the recent advances in 21st century medicine is the emergence of gene therapies, drugs that affect the basic biology of genetic disease. The field has seen some notable setbacks in the past, but in recent years has exploded as decades of basic science have been successfully translated into the most complex biologics ever constructed, leading to regulatory approval of several gene therapy products in oncology, hematology, neurology, and ophthalmology indications. These drugs are at the apex of biological manufacturing complexity, and have the potential to be disease modifying or even curative. Evidence-based and innovative quantitative clinical development and lifecycle management strategies will be required as fixtures in the development for these unique drugs in order to reach patients in need.
Development of Gene Therapies: Strategic, Scientific, and Regulatory Considerations is an unparalleled summary of the current scientific, statistical, developmental, and regulatory aspects of gene therapies, which is fast becoming a core area of the biopharmaceutical industry. This edited volume provides a systematic description of core development topics in gene therapies through 19 peer-reviewed chapters written by subject matter experts in the field.
This edited volume is an invaluable resource for business leaders and investors hoping to understand the scientific principles and strategy of a company they may potentially invest in; the family members of someone affected by a genetic disease who wish to understand better how these therapies work and what they might expect as a treatment for a loved one; academic professionals, who want to learn and teach incoming medical, public health, or business students; and seasoned drug developers, who wish to learn more about the about the cutting edge of biopharmaceutical drug development.
Key Features:
Provides a thorough background on the scientific, manufacturing, and translational concepts and competencies for gene therapies. Covers important strategic aspects of the gene therapy industry, thereby helping investors, drug developers, and regulators gain a better appreciation of the potential value of gene therapies. Expounds on many existing and emerging state-of-the art scientific and technological advances, as well as ethical, pharmacovigilance, and regulatory considerations for gene therapy product development. Presents several case studies of successful development of gene therapies, including two of the most remarkable FDA-approved gene therapy products: Zolgensma and Luxturna. Provides perspectives and forward-looking statements on the future of gene therapies in neurological, in utero, and ultra-rare indications.
1. Introduction: The Road to Gene Therapy 2. Driving AAV Drug Design to the Right Place, Right Amount, and Right Time 3. A Practical Guide to the Nonclinical Development of In Vivo Gene Therapies 4. Quantitative Systems Pharmacology Modeling of Adeno-Associated Virus Gene Therapies: Mechanistic Identification of Species-Translation Using Preclinical and Clinical Data 5. Bringing Gene Therapy to Patients: A Clinical Development Perspective Based on Brain and Neuromuscular Diseases 6. The Ethics of Gene Therapy 7. AAV Vector Immunogenicity in Gene Therapy: Mechanisms, Assessment, and Immunomodulation Strategies 8. Prenatal Somatic Cell Gene Therapy 9. Development of Gene Therapies for Ultra-Rare Disease 10. Statistical Innovation for Gene Therapy Development: Clinical Trial Design and Analysis Considerations 11. Biomarkers in Gene Therapy Development for Rare Diseases 12. Manufacturing, Analytical, and Process Comparability Challenges for Recombinant Adeno-Associated Virus (rAAV) Gene Therapy 13. Regulatory Considerations in the Development of Gene Therapy Products 14. Gene Therapy Clinical Safety Considerations: Short- and Long-Term 15. Development of Gene Therapies from an Academic Perspective 16. Commercial Models, Access Hurdles, and Health Economics of Gene Therapies 17. The Zolgensma Journey: A Groundbreaking Therapy for SMA 18. History and Development Story of Luxturna: Scientific and Regulatory Challenges 19. The Future of in vivo rAAV Gene Therapies for Rare Neurological Diseases
Avery McIntosh, Ph.D. is a drug developer working in rare diseases at Pfizer. He received his M.Sc. and Ph.D. in biostatistics from Boston University with a dissertation on Bayesian methods to model household tuberculosis transmission. He has managed teams of statisticians across study phases and in a variety of drug types and disease areas, including neurology, ophthalmology, infectious disease/ global health, hematology, and oncology. He has published peer-reviewed articles on various topics in drug development and biostatistics, including development of cell and gene therapies and qualification of digital endpoints in neurological diseases. Oleksandr Sverdlov, Ph.D. is a Neuroscience Disease Area Statistical Lead at Novartis. He received B.Sc. in Applied Mathematics from V.N. Karazin Kharkiv National University, Ukraine, M.Sc. in Statistics from University of Maryland, Baltimore County (UMBC), and Ph.D. in Information Technology with Concentration in Statistical Science from George Mason University. He has been actively involved in methodological research and applications of innovative statistical approaches in drug development. He has co-authored over forty refereed articles, edited two monographs, and co-authored a book Mathematical and Statistical Skills in the Biopharmaceutical Industry: A Pragmatic Approach (CRC Press/Chapman & Hall, 2019). His most recent work involves design and analysis of clinical trials evaluating novel digital technologies
