Pharmacogenomics in Drug Discovery and Development − Rakyat Biologi

The new knowledge of genetic biomarkers for diseases is spurring the development of pharmacogenomic-based drugs discovery and development strategies that allow pharmaceutical companies design more individualized drug regimens and dosages (Wechsler, 2001). This is accomplished by identifying genetic conditions that allow individuals to be more likely to respond to certain drugs, not respond at all or be susceptible to adverse reactions (Bernard, 2003; Whittaker, 2003; Wechsler, 2004).

Several studies have cited adverse drug reactions to be one of the leading causes of death among hospitalized patients, contributing the majority of the $17 to $29 billion annual costs of medical errors (Lazarou et al., 1998; Kohn et al., 1999; Prows & Prows, 2004). Kohn et al., (1999) also note the cost associated with the loss of confidence in the healthcare system and the diminishing satisfaction of both patients and health professionals.

Pharmacogenomics is expected to reverse this trend by enabling pharmaceutical companies to design drugs that meet the needs of pre-defined genetic sub-groups of the general population (Rioux, 2000). Pharmacogenomics cannot and does not improve the efficacy of a given drug; it simply helps in selecting patients who are likely to respond well (Rioux, 2000). The main interest is in identifying patients for whom drug efficacy can be predicted, and to spare others from avoidable adverse effects (Rioux, 2000). The promise of pharmacogenomics is that physicians may soon be able to prescribe drugs on the basis of their patients’ genetic profiles (Prows & Prows, 2004; Zemlo, 2004). This would take away the guesswork in drug prescriptions, increase both physician and patient confidence and radically modify the prevailing approaches to drug discovery and development, diagnostics, therapies and disease prevention strategies (Prows & Prows, 2004; Zemlo, 2004). There is also a benefit to society as the use of expensive drugs is avoided in patients whose ailments clearly would not have been abated or cured by these drugs (Rioux, 2000).

As noted earlier, adverse drug reactions in the general population often results in hospitalizations and in some cases fatalities (Lazarou et al., 1998; Kohn et al., 1999; Prows & Prows, 2004). When these drug reactions are investigated and documented, and the culprit drug identified, the result commonly is a withdrawal (or recall) of the drug (Bernard, 2003). This is immediately followed by a torrent of lawsuits for negligence and pharmaceutical malpractice (Simons et al., 2004). A pharmacogenomic drug development strategy presents an opportunity to reverse this trend (Bernard, 2003; Zemlo, 2004). The promise of pharmacogenomics may lead to the “accelerated development of precision pharmaceuticals” (Zemlo, 2004). Precision pharmaceuticals refer to drugs (and dosages of these drugs) that are tailored to an individual’s genetic composition (Bernard, 2003; Zemlo, 2004). These drugs according to Zemlo (2003) can be can be evaluated in simplified and shortened clinical trials and because of their customization will show little or no adverse effects. With drug customizations, some form of genetic testing or verification may be required prior to prescription (Bernard, 2003). This ensures that the chances for wrong prescriptions are greatly minimized (Bernard, 2003).

In the course of drug discovery and development, pharmaceutical companies stay mostly focused on the major blockbuster drugs that are prescribed to upwards of 20 million people (Klein & Tabarrok, 2003; Drews & Duyk, 2004; Tait and Mittra, 2004). The result of this is a drug loss – a loss of drugs that may have been developed to cure diseases that affect only a small number of people (Klein & Tabarrok, 2003). These drugs – or potential drugs are abandoned or orphaned (Klein & Tabarrok, 2003). A pharmacogenomic strategy to drug development may revive these orphaned drugs if it can be demonstrated that there are potential beneficiaries for these drugs (Bernard, 2003). Similarly, Rioux (2000) has suggested that “from an economics standpoint, if the pharmaceutical company could benefit from something like orphan drug status for its product, this would help encourage stratification of populations on the basis of pharmacogenomics, since the reduction in the size of a population to be treated could be offset by preference for the drug”. This according to Rioux (2000) is the only way that pharmaceutical companies can be encouraged to forgo the blockbuster dogma.

The FDA in recent years has recognized and even encouraged pharmacogenomic approaches to drug discovery and delivery (Rioux, 2000; Wechsler, 2004). As pharmacogenomic technologies continue to emerge and mature, the FDA as well as other international regulatory bodies is developing pharmacogenomic guidelines and regulations (Bernard, 2003). In fact, the FDA is encouraging pharmaceutical companies to conduct pharmacogenomic research and submit results to a proposed “Interdisciplinary Pharmacogenomic Review Group” – a group that is not directly involved in the drug approval process (Bernard, 2003). Notwithstanding the increased attention and the documented potential and promise of pharmacogenomics-based drug development strategies, there has been continuous resistance to this approach on the part of pharmaceutical companies (Rioux, 2000; Bernard, 2003; Wechsler, 2004). This resistance is borne out of the perception that a pharmacogenomics strategy will lead to a significant loss of revenues resulting from the fragmentation of the drug market (Rioux, 2000; Bernard, 2003). Bernard (2003) in his article “The 5 Myths of pharmacogenomics” lists as the 4^th myth, the perception that pharmacogenomics will diminish the much coveted blockbuster drug model. He goes on to debunk this “myth” by demonstrating the potential market-increase impacts of pharmacogenomics. In the diagram below, Bernard (2003) shows a holistic representation of the possibilities with pharmacogenomics.