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The ultimate goal is for the medical system to develop new evidence as a natural by-product of delivering appropriate care
The personalized-medicine bandwagon is on a roll, paralleling the death-knell for blockbuster-drug development. Strategies for identifying patients who will respond to a certain therapy, as well as those most likely to suffer adverse events, promise to improve healthcare quality while also eliminating waste and inappropriate spending. Interventions based on individual characteristics may have limited sales, but they may justify higher prices and reduce the high cost of clinical development.
The flip side is that personalized medicine means developing research and marketing strategies for therapies that work in maybe half the population. Diagnostics have to be incorporated into these programs, which adds to development costs and treatment expense. It's not clear whether personalized medicine represents the new frontier of biomedical development or is something that will never be more than niche products.
These issues are gaining attention in industry and health-policy circles. Last month, a conference at the Harvard Medical School explored strategies for accelerating personalized-medicine adoption. At a September conference in Washington hosted by the Personalized Medicine Coalition (PMC), Department of Health and Human Services Secretary Mike Leavitt unveiled a federal report on personalized healthcare that outlines numerous HHS projects for developing biomarkers, expanding health IT, and translating genomics discoveries into evidence-based medicine for clinicians.
For example, the National Institutes of Health (NIH) is funding dozens of studies to identify genetic factors related to cancer, heart disease, obesity, AIDS, diabetes, and others. Researchers can use this information to validate new biomarkers and other tools for defining individual differences affecting disease. These results can lead to new diagnostics that identify patients more susceptible to disease and likely to benefit from preventive care and treatment.
Successful treatment requires physicians to use patient genetic information in deciding whether to conduct assays and revise prescribing. Medical societies are beginning to support such approaches, as seen in recent recommendations from the American Society of Clinical Oncology (ASCO) that back the use of certain genomic tests in deciding appropriate treatment for breast cancer patients. An HHS advisory committee is preparing a report on the ethical and medical issues associated with incorporating genetic testing into clinical practice.
Efforts to ensure that clinical decisions are based on accurate and timely evidence are expanding under the Agency for Healthcare Research and Quality and the Institute of Medicine's Roundtable on Evidence-Based Medicine. The ultimate goal is for the medical system to develop new evidence as a natural by-product of delivering appropriate care.
Such an approach requires an electronic medical-record system that can store and access information on patient genetic disposition, treatment, and response. The Leavitt report outlines multiple initiatives for establishing an e-health system, but that still may be years away. It notes that accumulating data on individual genetic markers for disease raises concerns about the need for privacy and security to ensure that personalized medical information is not misused.
New discoveries on how variations in the human genome affect an individual's response to medications offers exciting opportunities for pharma. Researchers say that people with certain genetic factors may be less likely to resume smoking following smoking-cessation treatment. A report from the National Institute of Mental Health indicates that genetic variation in patients may relate to suicidal thoughts when taking antidepressants. Information on gene variations already is providing more-accurate chemotherapy dosing for children with leukemia and promises to refine treatment for those with asthma.
The Food and Drug Administration has championed the shift to personalized medicine as key to modernizing drug development and producing more high-value therapies. A prime goal of its Critical Path Initiative is to identify and validate biomarkers and other tools for determining the safety and efficacy of drugs in certain patients. Agency officials have found that dose-response differences can decrease adverse events, and categorizing patients according to response potential can increase treatment effect and lead to more informed labeling.
FDA has encouraged sponsors to incorporate genomic data into clinical and toxicology studies through its Voluntary Genomic Data Submission (VGDS) program. The agency has discussed some 50 protocols under the program, has developed guidance for submissions, and recently expanded VGDS into VXDS to include additional "'omic" data.
More cancer drugs are being approved for patient subsets as a result, as well as diagnostics for genomic markers. But the availability of new tests does not necessarily shift medical practice [see sidebar]. Links between tests and treatments have raised questions about the viability of drug-diagnostic codevelopment. Pharma companies are using diagnostics in clinical development of new therapies and incorporating test information into drug labeling. But sponsors have opposed explicit FDA policies for bringing a validated diagnostic to market along with a new therapy, as outlined in an FDA concept paper issued in 2005.
Getting the Warfarin Dose Right
In addition to its impact on diagnostic development, the shift to targeted medicines may influence broader changes in clinical trial design and conduct. FDA officials believe that "personalized" clinical trials structured to identify responsive or at-risk subgroups will be able to determine correct dosing, reduce toxicity, and monitor response at lower cost and with more likelihood of success. However, Dan Mendelson, president of Avalere Health, fears that targeted clinical development may be more expensive and complex. He expressed skepticism at the PMC conference that sponsors will be able to use genetic testing to eliminate nonresponsive individuals from trials and noted that clinical trial sample sizes may have to be larger to obtain meaningful data on subgroups.
Perhaps the most important gain from targeted medicines lies in the potential to avoid adverse events in clinical research and after a drug comes to market. Earlier information on why beneficial drugs cause severe reactions in some individuals could prevent the loss of drugs like Vioxx, says George Downing, director of the HHS personalized healthcare initiative.
A number of collaborations aim to identify genetic markers that may help predict which individuals are at risk for serious drug-related adverse events. The International Serious Adverse Events Consortium (SAEC), which includes Abbott, GlaxoSmithKline, Johnson & Johnson, Pfizer, Roche, Sanofi-Aventis and Wyeth, is examining whether genetic data can be linked to drug-related liver toxicity and the rare skin condition called Stevens–Johnson Syndrome (SJS). The plan is to examine DNA for evidence of certain side effects in individuals taking certain drugs. If successful, the consortium might examine cardio problems or kidney disease associated with certain medicines.
Health plans, insurers, and PBMs are looking to pharmacogenomic data to better inform drug coverage and reimbursement. Current drug-pricing models are under considerable pressure, particularly as US consumers face copays of up to 25 percent for certain critical drugs.
The solution lies in shifting the drug-reimbursement system to reward treatments that provide better quality at an overall lower cost of care, explained former FDA commissioner Mark McClellan at the PMC conference. Medco is assessing whether genetic testing can identify those patients most likely to benefit from the use of tamoxifen to prevent breast cancer. The information should help reduce wasted spending and steer nonresponsive patients to more effective alternative treatments.
Pharma marketers are looking at innovative drug-pricing models to gain coverage for high-cost specialized medicines. Some manufacturers are offering capped-population pricing and other risk approaches, where the company guarantees a payer a certain expenditure based on outcomes of a targeted patient population.
Personalized medicine also may change pharmaceutical sales and marketing strategies, such as compensating sales forces based on how well they encourage effective drug use, instead of just sales volume. Business models for personalized medicine feature smaller, more targeted clinical trials, risk-based pricing, and marketing approaches that emphasize physician education and incorporate diagnostic testing.
Jill Wechsler is Pharmaceutical Executive’s Washington correspondent. She can be reached at firstname.lastname@example.org