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Thursday, November 6

Session II:

PHASE III & IV CLINICAL TRIALS

7:30am Morning Coffee 
(Breakfast Technology Workshop Sponsorship Available)

8:25 Chairperson’s Remarks

8:30 The Benefits and Risks of Predictive Pharmacogenomic Tests
Lawrence J. Lesko, Ph.D., Director, Clinical Pharmacology Biotherapeutics, FDA 
The adoption of predictive pharmacogenomic tests, such as CYP 2C9 and VKORC1 for warfarin, into patient care is predicated on their clinical utility. The problem is that there is no universal agreement on what clinical utility means. This presents major challenges in deciding on what genomic biomarkers to qualify for a specific purpose, as well as what weight of evidence is needed to qualify them for clinical decision-making. In a broad sense, clinical utility of a predictive test refers to the benefit of a true test result and the harm of a false test result. As with drugs, clinical utility encompasses many diverse points of view into an overall benefit/risk assessment. This becomes necessarily a case-by-case situation, because stakeholders such as healthcare providers, patients and third party payers are likely to have different points of view. This presentation will consider this conundrum using specific examples of drug/test combinations. 

9:00 Establishing Utility of Genetic Tests
Felix Frueh, Ph.D., Vice President, Personalized Medicine, Medco Health Solutions Inc 
The call for randomized clinical trials (RCTs) to establish the clinical utility of genetic tests continues to hamper the uptake of genetic testing in clinical practice. Although one might consider RCTs the gold standard for any introduction of a new medical tool into clinical practice, medicine has evolved over centuries through the uptake and use of habits and tools deemed useful based on observations and retrospective analysis of data. Now that we are rapidly approaching a time in which complete genetic information for a patient either already exist or is easily obtained, e.g. via whole genome scans or whole genome sequencing, the focus of establishing the clinical utility of a genetic variation - and using this information in clinical decision making - will shift from ‘should this test be ordered?’, to ‘can I afford to ignore it?’. It is therefore reasonable to assume that the easy access to genetic information will reduce the call for RCTs and observational data will be used more and more to make treatment decisions for which a genetic association has been found.

9:25 Pharmacogenetic-Based Dosing of Warfarin: Will Accurate Prediction of Therapeutic Dose Improve Clinical Outcomes?
Charles S. Eby, M.D., Associate Professor, Departments of Pathology & Immunology and Medicine, Washington University School of Medicine
Warfarin is an effective oral anticoagulant but has a wide and unpredictable therapeutic dose range leading to bleeding and clotting complications during initiation. Numerous algorithms, based on clinical and genetic factors that affect warfarin dose response, improve the accuracy of wafarin dosing, but it is not clear whether pharmacogenetic-based warfarin dosing will lead to improvement in clinically meaningful endpoints. Results of retrospective and prospective studies will be reviewed and the design and goals of a multicenter randomized trial scheduled to begin in late 2008 will be presented.

9:50 Coffee Break, Poster & Exhibit Viewing

10:30 Integration of Pharmacogenomics in Clinical Trials: The Case of Anti-Atherosclerotic Approaches
Jean-Claude Tardif, M.D., Director, Research Center, Montréal Heart Institute 

10:55 Pharmacogenetics: Beyond Cholesterol Lowering Effects
Issam Zineh, Pharm.D., Assistant Professor of Pharmacy Practice and Pharmaceutics, College of Pharmacy; Assistant Professor of Cardiovascular Medicine, College of Medicine; Associate Director, University of Florida Center for Pharmacogenomics 
Statins are among the most commonly used cardiovascular drugs worldwide. It has been suggested that statins may have ancillary health benefits beyond their ability to lower cholesterol. This presentation discusses the potential of pharmacogenetics to identify which patient sub-populations may experience these benefits.

11:20 Drug Transporters and Individualized Drug Therapy
Richard B. Kim, M.D., FRCP(C), Professor of Medicine, Physiology & Pharmacology Chair, Division of Clinical Pharmacology; Director, Centre for Clinical Investigation & Therapeutics, Schulich School of Medicine & Dentistry, University of Western Ontario 
Historically, metabolism had been viewed as the main determinant of drug disposition. In recent years however, clear evidence has emerged to suggest that drug transporters expressed in organs such as the liver, intestine, and kidney are critically important to drug absorption, distribution, and elimination. Not surprisingly, genetic variation in such transporters are now becoming much more appreciated as determinants to response to drugs such as the statin class of lipid lowering drugs, and the efficacy of a number of anticancer drugs. In this session, examples of key transporter genetic variations and their impact to drug therapy will be provided. Inclusion of drug transporter pharmacogenomics will prove to be essential to the goal of individualized or personalized medicine.

11:45 Regulatory Polymorphisms as Biomarkers in Pharmacogenomics
Wolfgang Sadée, Ph.D., Professor and Chair, Pharmacology, The Ohio State Medical Center 
We have developed a generic approach to finding hidden regulatory polymorphisms in key candidate genes relevant to drug therapy. We have applied this approach to several key genes such as DRD2, ACE, CYP3A4, and VKORC1, finding novel and frequent polymorphisms or validating existing ones in each case, and testing their impact in clinical trials. Regulatory polymorphisms in these four genes have excellent potential for the development of drug label biomarkers.

12:10pm Expert Panel: Discussion of Goals and Challenges from Speaker Summation Slides
Moderator: Michael Phillips, Ph.D., Director of Pharmacogenomics, Génome Québec; Associate Professor, Université de Montréal 

12:40 Luncheon Workshop Sponsored by   

Potential for Use of GWAS Results in Drug Development and Pharmacogenomics
John W. Hooper, Ph.D., President and CEO, Genizon BioSciences
Genizon has completed 10 genome wide association studies (GWAS) in common diseases and traits.  Examples will be shown of discoveries from these studies with potential for novel drug targets, pre-symptomatic and discriminatory diagnostics, biomarkers for patient selection to optimize drug response, drug rescue and expanded therapeutic indications.

Session III:

POST-MARKETING SURVEILLANCE AND RISK MITIGATION STRATEGIES

2:00 Chairperson’s Remarks

2:05 Post-Market Surveillance and Surveillance Network
Gideon Koren, M.D., FRCPC, FACMT, Director, The Motherisk Program, The Hospital for Sick Children; Professor of Pediatrics, Pharmacology, Pharmacy and Medical Genetics, The University of Toronto; and Professor of Medicine, Pediatrics and Physiology/Pharmacology and the Ivey Chair in Molecular Toxicology, The University of Western Ontario
Codeine is metabolized by cytochrome P4502D6 to the active morphine. Some persons are Ultra rapid 2D6 metablizers, leading to morphine toxicity after codeine. After a fatal case of an opioid toxicity in a breastfed infant of an Ultra rapid metabolizing mother, we conducted a case control study to identify the pharmacogenetics of CNS toxicity in breastfed infants whose mothers used codeine for pain after delivery.

2:30 Post-Marketing Risk Mitigation
Ming Ji, M.D., Executive Director, Amgen Global Safety 
Recently passed legislation FDA Amendments Act (FDAAA) establishes substantial changes to the way in which the U.S. FDA looks at drug safety and pharmacovigilance. The FDA may require a sponsor to conduct post-approval clinical study or trial (at any point in a product’s lifecycle) to assess a known serious risk, signals of a serious risk or identify an unexpected serious risk. This session is to provide an overview of FDAAA requirements on Risk Evaluation and Mitigation Strategy (REMS)’ in support of post marketing safety surveillance and risk minimization activities.

2:55 Refreshment Break, Poster & Exhibit Viewing

3:30 The Economics of Pharmacogenomics in the Post-Approval Period: Do the Numbers Tell a Story?
Christopher-Paul Milne, DVM, MPH, JD, Associate Director, Tufts Center for the Study of Drug Development, Tufts University 
Some studies suggest that 10-20% of new drugs may be withdrawn or severely restricted post-approval due to safety concerns. At the same time, efficacy of drugs prescribed for broad patient populations can run as low as 35%. The application of molecular profiling for drug response could help to change these numbers. But other numbers have to be factored in first. This presentation will consider several questions about the economics of pharmacogenomics (PGx) in the postapproval period: 1) What do we know now about the economics of PGx post-approval for drug salvage (late-stage failures, withdrawn/black-boxed, “mini-busters”, etc.), and going forward, what are the best case, worst case and “real case” scenarios based on what we know and don’t know?; 2) What are the economic implications of pharmacogenomics for post-approval risk management, disease management, and comparative effectiveness decisions?; 3) What do government payors say, and more importantly, will they pay for PGx - reflections on NICE, CMS, Canada’s Progressive Licensing Project, etc.?

3:55 Lessons for Post-Marketing Surveillance 
Maryse St. Louis, Ph.D., Hema Québec 
More than 250 blood group antigens have been described to date. Most are the result of single nucleotide polymorphisms opening the possibility of DNA-based technology. In order to facilitate massive screening of the most clinically significant minor blood group antigens, a fruitful collaboration between the teams of Drs. Michael S. Phillips (Genome Quebec) and Maryse St-Louis (Héma-Québec) led to the development of a unique genotyping platform. This work enabled Héma-Québec to create a permanent database of donors genotyped for several of these blood antigens to facilitate the finding of compatible blood for many patients in need of a specific blood profile transfusion. Transfusion medicine greatly benefits from genotyping.

4:15 Close of Conference

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