Product Development for Public Health & Emerging Infections

Transcription

1 Product Development for Public Health & Emerging Infections Michael G Kurilla, MD-PhD Director, Office of BioDefense Research Affairs Division of Microbiology & Infectious Diseases Associate Director, BioDefense Product Development National Institute of Allergy and Infectious Diseases May 23,

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8 Pre-2001 Capability Reagent Repository Bacterial respiratory pathogens Viral research reagents Malarial reagents Services In vitro / in vivo antiviral testing (non-glp) Tuberculosis vaccine testing (non-glp) Clinical Evaluation Vaccine Treatment and Evaluation Unit Collaborative Antiviral Study Group Bacteriology & Mycology Study Group Tuberculosis Research Unit Focus: Targeted resources directed towards specific recognized needs 8

9 Example of Flexible Capacity: Seasonal and Pandemic Flu Genomic efforts >2000 full genomic sequences in Genbank Reagents Pabs, Mabs, & recombinant proteins Drug Development Multiple in vitro / in vivo screening efforts; combination studies Animal Model Development GLP H5N1 ferret/mouse models Candidate Pilot Lot Production Clinical grade H5N1 vaccines Influenza challenge viruses Preclinical Studies Support H5N1 immunoassays GLP toxicology of adjuvanted H5N1 vaccine candidates Proof of concept studies for vaccines, adjuvants, & drugs Clinical Development Multiple Phase I/II trials of H5N1 Phase III trial of GSK s Fluarix for licensure Chart review for oseltamivir in children <1 year Evolving Threats Anti-microbial resistance Potential to defeat existing therapies Naturally occurring Near term intentional activity Enhanced virulence Potential to enhance infectiousness and reduce therapeutic window Mid term potential activity Chimerism / Immunomodulators Potential to defeat existing diagnostics & preventive strategies Long term potential activity 9

10 Current Situation: Market Failure Supply = Push Research provides new opportunities that lead to innovation. Demand = Pull Respond to the needs of the marketplace. Need to be flexible, contractual, committable, not to be subject to political change. NIH Provider of acquisition $$ Product Development Prerequisites Concepts Identification of targets or points of intervention based on scientific understanding of the ID troika Microbiology Immunology Pathogenesis Capabilities Infrastructure to support activities and services necessary to evaluate candidate products (safety / efficacy / technical) Cash Funding mechanisms beyond traditional R01 grants 10

11 NIAID Product Development Portfolio Basic Research Microbiology/Immunology/Pathogenesis Critical mass for novel concepts generation & evaluation (broadly applicable to public health needs) Applied Vaccines/Therapeutics/Diagnostics Representative mix of traditional versus innovative concepts Advanced Develop successful Applieds through IND/Phase I Further development based on programmatic needs (with substantial input from DHHS/DHS) Strive for balanced portfolio Integrated Product Development NIH Activities HHS Activities BARDA BioShield/Flu Basic Applied Product Development Acquisition Basic Fundamental Science Applied Target identification Screening Animal model development Early Advanced End-Stage Early Advanced Pilot lot production Preclinical studies Animal efficacy models Phase I/II clinical trials End-Stage Commercial scale development EUA-enabling studies Large scale safety trials Animal rule efficacy studies Regulatory filing activities 11

12 The traditional way Assessment / Prioritization One bug one drug/vaccine/dx At ~ 15 years and $1B per product Homeland Security Presidential Directive (HSPD) - 18 Evolving Threat Landscape Principles & Approaches Traditional What we know Enhanced Resistance Emerging New agents Advanced Engineered Focus on threats with greatest potential for catastrophic consequences Agent specific countermeasures for greatest threats (Tier I) Flexible defenses for remainder (Tier II) 12

13 NIAID vision of flexible defenses Broad Spectrum Approaches Activity (products) Products applicable to classes of threats Includes host directed interventions Immunomodulators Technology (product enhancements) Temperature stabilization Alternative delivery devices Vaccine adjuvants Platforms (production) Standardized manufacturing systems (another egg) Towards the Future Vaccines non-needle delivery long term stabilization multivalency (cross protection) faster induction adjuvants (rationale design & selection) Therapeutics true broad spectrum innate immune augmentation host based directed interventions Diagnostics multiplexed adaptive platforms rapid POC, clinical decision making impact host based systems 13

14 Addressing Biological Threats Potential applicability of technology and/or platform monoclonal antibodies novel adjuvants intranasal vaccine most vaccines & antivirals Single Agent multivalent vaccines Manufacturing platforms Adjuvant mix many antibiotics; few antivirals Multi Agent Vaccination enhancements few antibiotics Target / Mechanism magic bullets Broad Spectrum Host based targets Immunomodulators Genomically derived broad spectrum targets current frontier 14