Biomarkers in Drug Discovery and Development
Dr. Stefano Persiani is currently Director of Translational Sciences and Pharmacokinetics at Rottapharm Biotech, Italy. He graduated in Pharmacy at the University of Milan, Italy and completed a Post-Doctoral fellowship in the Department of Pathology of the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA, and later as a Research Associate in the Department of Pharmaceutics of the University of Southern California, School of Pharmacy in Los Angeles, California, USA. After these academic positions, he entered the pharmaceutical industry at Farmitalia Carlo Erba, Pharmacia, Upjohn, and Zambon Group and in the CRO sector as Scientific Director for Clinical Pharmacology. Dr. Persiani in his current role applies translational approaches from drug discovery to development and registration in several therapeutic areas. Dr. Persiani is a member of various international scientific societies and serves on the review board of numerous professional journals. Dr. Persiani acts as an external expert evaluator for the European Commission on the 7th Framework Program, Maria Sklodowska-Curie Individual Fellowships, HORIZON 2020, and Innovative Medicine Initiative. Dr. Persiani is also an expert evaluator for La Caixa Foundation (a bank foundation) where he evaluates and provides recommendations to the bank on applications requesting funding. Dr. Persiani is a faculty of Pharmaceutical Training International and Training.com where he provides training to pharmaceutical executives in several fields of Translational Sciences.
High development costs and low success rates in bringing new medicines to the market demand more efficient and effective approaches. The FDA supports model-based drug discovery and development. This represents a mathematical and statistical approach that constructs, validates, and utilizes disease models, drug exposure-response models, and pharmacometrics models to facilitate drug discovery and development. Biomarkers, providing quantitative information on a drug safety and efficacy, allow the implementation of quantitative pharmacology. Biomarkers are fundamental to understanding the key characteristics of new molecular entities in a quantitative manner, with the goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans and enabling critical decision-making. Biomarkers are extremely valuable in these respects. Biomarkers can be classified based on their applications as diagnostic, prognostic, predictive, and pharmacodynamics. Being able to asses both safety and efficacy, biomarkers can provide a preliminary evaluation of the safety margins during drug discovery and development. Biomarkers are useful in both preclinical and clinical pharmacology for the implementation of the learning/confirming paradigm. Additional uses of biomarkers in clinical trials are to obtain the Proof of Mechanism (the ability of the drug to reach the therapeutic target), the Proof of Principle (the ability of the drug to affect the disease phenotype), and (if surrogate endpoints) the Proof of Concept (the ability of the drug to be clinically beneficial). When used to assess the response to a therapeutic intervention, pharmacodynamics biomarkers that are surrogate endpoints can allow the assessment of the clinical benefit of an investigational new drug without the need to conduct lengthy and more expensive clinical trials based on clinical endpoints.
Biomarkers may provide information such as:
- Mechanism of action of the drug
- Metabolic profile
- Dose selection (PK/PD modeling)
- Evaluation of dose-response
- Personalized medicine and companion diagnostic
- Candidates that are likely to fail
An important application of biomarkers is for the streamlining of clinical trials. In this paradigm, biomarkers are used to identify those patients who are most suitable for a treatment. Specifically, genomic biomarkers can be used to identify patients with a particular disease sub-type or severity with a high chance of benefiting from a particular medicine (precision medicine) and to exclude patients at increased risk of serious side effects (adverse reactions). Examples are Umbrella and Basket trials in oncology. Biomarkers to be used in clinical trials must be validated to ensure that the biomarker test is sufficiently accurate, reliable, sensitive, and specific. Therefore, the method used for the determination of the biomarkers in biological fluids must fulfill these criteria. Both industry and regulators such as the FDA are moving away from validation and moving towards qualification, i.e. a less strict validation. Qualification allows relative rather than absolute answers and allows contextualization, however, there is little guidance on how to qualify biomarkers, and definitions are still confusing.
Biomarkers offer great potential for empowering decision making at early stages of drug discovery and development, allow cost reduction and accelerate drug development. However, sizeable investment of both time and money have hampered the implementation process of biomarker discovery and development. In addition, different skills and technologies are needed.
The webinar will provide an overview of the critical aspects described above related to the use of biomarkers in drug discovery and development. This should benefit all the stakeholders within the pharmaceutical industry and CRO sectors that are involved in drug discovery and development.
- Definition of biomarker
- Classification and types
- Surrogate endpoints as a special class of biomarkers
- Biomarkers use
- Role of biomarkers in drug discovery and development
Course Level - Basic
Who Should Attend
Junior Scientists, Senior Scientists, and Middle Management
Why Should Attend
Major advances in the basic science of drug discovery and development have led to an enormous increase in the number of new drug targets. However, despite increasing commitments of time and money to the effort, these advances have not culminated in an increase in new drug approvals. The FDA, in the Critical Path Initiative, has therefore defined the current drug discovery and development approach as inefficient. The Agency indicated that the limited capacity to predict the safety and efficacy of investigational new drugs is in part responsible for this inefficiency. Consequently, efforts to improve this process are being implemented across the continuum of drug discovery and development activities. The use of biomarkers to identify the most promising drug candidates may ultimately allow a more economical and timely application of developmental resources as biomarkers can provide useful information on the drug safety and efficacy. Biomarkers, typically laboratory and other measures, to monitor therapeutic progress, disease progression, the efficacy of interventions, and adverse events should streamline drug discovery and development. Biomarker use is becoming more and more popular to the extent that drug development without the use of biomarkers is nowadays considered at increased risk of failure. The use of biomarkers should allow proper go-no-go decisions as it should allow not only to predict the safety and efficacy of an investigational new drug but it should also allow a preliminary comparison with existing drugs on the market. This should ultimately yield a preliminary indication of the market value of a new drug for a proper investment justification.
- Speaker: STEFANO PERSIANI
- Webinar Code: STEF-0001