Defining the Industry's Next Chapter
Genomic advances will, in all likelihood, translate to significant advances in drug development at some point in the future. Investors, however, appear disappointed that the initial mapping of the human genome did not produce more immediate therapeutic breakthroughs and seem to have quickly discounted its impact.
Yet, while genomics-directed drug development may remain a distant event, genomic advances seem poised to have a profound impact on dictating prescription patterns in the near term. The emerging use of biomarkers provides clear evidence of this trend.
It is often the case that certain people derive more benefit from one drug of a particular class than another medication in that same class. This is the reason a number of the cholesterol-lowering statins have achieved blockbuster sales status, for instance. Such differences in response are increasingly being linked to genetic variation among individuals.
The implication of the link between response and genetic variation would be the ability to prescribe medicines based on genetic profile. Examples of this application are just now beginning to emerge.
Consider maraviroc, the first in a new class of anti-HIV therapeutics being developed by Pfizer(www.pfizer.com). Maraviroc works by blocking viral entry through the CCR5 pathway. In some 15% of newly infected patients, however, the virus accesses the host cell through an alternate CXCR4 entry against which maraviroc has limited effectiveness. In its Phase III trial, the company coupled the use of maraviroc with the Monogram Biosciences(www.monogrambio.com) assay to screen for CCR5-tropic patients. Pfizer plans to market the drug alongside the CCR5 assay. In April, an FDA advisory panel recommended accelerated approval of maraviroc.
Bucindolol, a beta blocker, provides further evidence that the long-awaited promise of biomarkers is at the cusp of realization. Bucindolol is a long-since-forgotten heart failure drug. Recent DNA analysis revealed that in heart failure patients with a particular genetic variant for a protein receptor on heart cells, bucindolol was highly effective, significantly more so than other beta blockers. This revelation led to the creation of ARCA Discovery, which is looking to commercialize this biomarker-linked therapeutic.
Yet, it is not readily apparent who would fund the clinical trials necessary to establish the widespread application of biomarker-guided drug selection, despite successes such as these. Historical prescription volumes could in some sense be considered artificially high as physicians have had only limited means to qualify users with any degree of accuracy.
Drug selection heretofore has largely been a trial-and-error process, with doctors often changing prescriptions repeatedly in the hope of identifying the best drug for a particular patient. According to a geneticist with a major pharmaceutical company, quoted in a 2004 San Francisco Chronicle article, “likely 90% of prescription medications work in only 30% to 50% of the people who take them.”
This apparent incongruity between therapeutic technology and the economic self-interest of drug companies explains in great part why, despite the FDA strongly encouraging the submission of biomarker data with NDA submissions, the industry has been dragging its feet.
If not the pharmaceutical industry, then who might take the lead to promote biomarker-driven therapeutics? Clearly significant investment in discovery as well as clinical trial validation would be required.
Economics have not rewarded participants in the diagnostic industry for making the investment necessary to advance such innovations. High volume at low cost continues to be the overriding operating philosophy of the industry. The few companies that have made the pharmaceutical-size investments to bring diagnostic advances to market have been unable to recapture that investment.
The managed-care industry could drive implementation as it looks for additional opportunities to control costs. Certainly the largest of these firms would have the economic clout to push change. Yet, as long as their policy holders continue to shoulder cost increases, managed care’s motivation to move aggressively seems uncertain.
Perhaps, though, it will be the pharmaceutical industry itself that ultimately become the champion of biomarker-linked medicine. While response-based patient segmentation would likely result in fewer prescriptions, it is unclear whether this would translate into less revenue. The pharmaco-economic case for reduced system-wide costs may likely support significant price increases. At the same time, the costs to bring new drugs to market would likely be substantially reduced. Clinical trials would be much more targeted toward specific patient populations. Marketing costs would also be dramatically reduced, as sales calls and ad campaigns become secondary to objective scientific criteria.
Likely, it will be the recognition of benefits such as these that will provide the impetus to overcome the sector’s initial aversion. And with it, the industry just might find a new rudder to guide its future course.