Personalized medicine: are payers the weak link?

Abstract

there is no codevelopment of tests. Tests are developed post hoc as a way of personalizing a drug, such as in the examples of abacavir and warfarin [8]. Despite the success stories, pharmaco genomics has had limited impact on clinical practice to date. The list of FDA/EMA-approved companion diagnostics is still relatively short, perhaps a dozen or so. There are significant clinical, financial and ethical barriers to the successful implementation of pharmacogenomics. Scientifically, the process of biomarker discovery and validation has been disappointingly slow. Additionally, regulatory and reimbursement issues have been problematic, particularly with respect to companion diagnostics, but also drugs that lack clinically effective diagnostics. To illustrate this point, gefitinib only works in approximately 10% of patients with advanced non-small-cell lung cancer. In June 2009, the FDA partially withdrew the drug, no longer allowing its prescription to new non-small-cell lung cancer patients, as no useful EGF receptor (EGFR) biomarker test is (yet) commercialized in the USA to pinpoint positive responders. As a result, gefitinib has encountered considerable market access issues, as payers are quite reluctant to reimburse. Even with FDA/EMA-approved biomarker tests lingering questions persist regarding their clinical effectiveness. A case in point is warfarin, which illustrates the acute translational gap that exists between knowledge and application. Tests suggest patients deficient in a certain enzyme activity (CYP2C9) may require a lower warfarin dose or more frequent monitoring and may be at risk of bleeding episodes. Since 2007, the FDA has been recommending genotyping for all patients being prescribed warfarin. In spite of this, in April 2009, the Centers for Medicare and Medicaid Services (CMS) decided not to routinely pay for genetic tests intended to help doctors determine Pharmacogenomics explores the ways in which genetic variations can be used to predict whether an individual patient will benefit from a drug, have a bad response or no response at all. Accordingly, therapies may be tailored to certain genetic characteristics of individual patients or subpopulations, drawing on data gathered from a variety of sources, including tests for biomarkers [1]. Knowledge of genetic variance can guide the selection of appropriate drugs or dosing tailored to an individual’s specific circumstances. This, in turn, may reduce the chance of adverse events, maximize the probability of better health outcomes and diminish costs [2,3]. In some instances, tests select which patients should or should not take a particular medication. For example, a test is used in conjunction with the breast cancer biologic trastuzumab to detect patients whose tumors overexpress HER2 protein [4,5]. In other cases, tests are used to predict the probability of adverse events associated with the use of a particular drug [6]. For example, there is a test which links hypersensitivity reactions to the HIV/AIDS drug abacavir to a specific genotype. Furthermore, there are tests which suggest ways to modify dosing in patients with an innately poor ability to metabolize a certain drug. In the case of warfarin, for instance, tests detect variations in the way individuals metabolize the blood-thinning agent. This may help to optimize dosing. Some personalized medicines are developed pharmacogenomically, concurrently with companion diagnostics. Trastuzumab was codeveloped with a pharmacogenomics test, which was US FDA/EMA approved and recommended prior to prescribing. There are also instances, such as the cancer biologic cetuximab, when a drug was codeveloped with a test but testing is not recommended by any regulatory authority prior to prescribing [7]. However, in most cases, at present “...in order to achieve widespread favorable reimbursement and clinical uptake for genetic tests and targeted therapies, manufacturers will need to bring more, and better, clinical evidence to the market place...”