FINAL THOUGHTS
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Tiffany P. Olson is the former president and CEO of Roche Diagnostics Corp. (Indianapolis). She can be reached at Olson_Tiffany @msn.com. |
In the past decade, a number of exciting breakthroughs have marked the beginning of the era of personalized, or genome-informed, healthcare, and pharmacogenomics is the foundation of this new kind of medicine. However, the greatest challenge IVD manufacturers and clinicians face is attempting to reap the potential benefits of personalized healthcare through the companion development of diagnostics and drugs.
In the late 1990s, there were several discoveries that significantly changed the development of personalized medicine. One such discovery revealed that approximately 25–30% of breast cancer patients have tumors with amplification and/or overexpression of the HER2 gene. Researchers also realized that this subset of patients responded well to treatment with trastuzumab (Herceptin), a monoclonal antibody. The subsequent years have seen other successes in pairing gene diagnostics with therapeutic treatment.
According to pharmacogenomics, a systematic correlation of genetic differences with variable responses to medications can enable the selection of the optimal patient therapy quickly, rather than after a lengthy trial-and-error approach. This strategy can potentially increase the drug’s efficacy while reducing adverse reactions and the overall cost of the treatment.
Parallel Searches
The research and development paths for diagnostics and drugs are often very different; however, the benefits of codeveloping a drug and a companion diagnostic can be substantial. At Roche (Basel, Switzerland), researchers are attempting to develop a feasible companion diagnostic test for a drug candidate whenever possible. In many cases, parallel assessment of multiple biomarkers is required. The process begins with researchers investigating variations in drug responses and the causes of such variations. Unfortunately, the work is still at an early stage. With limited knowledge available, the major challenge now is to develop a test that is sufficiently accurate in predicting patient response that can be integrated into clinical practice.
For example, Roche is working to develop and commercialize a cancer therapy that inhibits a mutated gene that has been associated with increased tumor aggressiveness and decreased survival rates. Simultaneously, researchers are developing an in vitro assay to screen for the mutated gene within the tumor tissue. If the project is successful, the IVD market will see a first-in-class oral cancer medicine that can be selectively administered to patients whose tumor carries the mutated gene.
There may be fewer “blockbuster” drugs for the pharmaceutical industry in the future, but there will be more-effective pharmaceuticals brought to market to meet the needs of patient subgroups. Although significant unanswered questions remain about the profitability of this approach for drug companies, FDA has now begun supporting the inclusion of pharmacogenomic data as part of submissions for new drug approval. FDA also has indicated that it will not use pharmacogenomic data included in submissions to prejudice the review and clearance of new drugs or to introduce additional burdens
during the drug approval process.
Encouraged by the potential benefits of personalized medicine, a small study conducted at Brigham and Women’s Hospital (Boston) examined the genes in cancerous tumors in four patients diagnosed with lung-sac mesothelioma. The researchers found that each patient’s tumor had a different set of mutations. David Sugarbaker, MD, who led the study, says, “Comprehensively surveying the mutated genes of patients’ tumors might help in determining which existing cancer drugs can work on which patients. What we need to do is pair up the right patient with the right drug.”
Although, in principle, pairing the right test with the right drug sounds elementary, in practice, it can be difficult to reconcile the occasionally conflicting and competing commercial interests between pharmaceutical companies and diagnostics.
However, the best way to resolve such potential conflicts is by remembering to keep in mind the value of reducing healthcare costs and, most importantly, the positive benefits for the patient.
