Personalized Medicine May Rationalize the Coverage of Specialty Therapies

The personalized medicine bandwagon is on a roll, offering a new model for calculating reimbursement of high-cost biotech therapies. 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 eliminating waste and inappropriate spending. Interventions based on individual genetic characteristics may have limited sales, but support higher prices and less costly clinical research methods.

Jill Wechsler

On the down side for manufacturers, personalized medicine means developing research and marketing strategies for therapies that work in only a small patient population. Diagnostics have to be incorporated into treatment regimens, which adds to development and payer costs. It's not clear if personalized medicine represents the new frontier of biomedical development or if it will only apply to niche products.

These issues are gaining attention in industry and health policy circles. At a September conference in Washington hosted by the Personalized Medicine Coalition (PMC), Health and Human Services (HHS) 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, macular degeneration, diabetes, and others. Researchers can use this information to validate new biomarkers and other tools to define 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.

TRANSLATION IS KEY

Successful implementation of personalized medicine requires physicians to tap 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 to decide appropriate treatment for breast cancer patients. An HHS advisory committee is preparing a report on the ethical and medical issues in incorporating genetic testing into clinical practice.

The campaign for evidence-based medicine encourages a shift to more personalized care. 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 round table 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 may be years away. It notes that accumulating data on individual genetic markers for disease raises concerns regarding the need for privacy and security to ensure that personalized medical information is not misused.

CHALLENGES FOR INDUSTRY

New discoveries on how variations in the human genome affect an individual's response to medications offer exciting opportunities for biotech manufacturers. The US Food and Drug Administration (FDA) has approved 20 therapies that use genomic information to target use, including several innovative cancer treatments. A report from the National Institute of Mental Health (NIMH) indicates that genetic variation in patients may relate to suicidal thoughts when taking antidepressants. Information on gene variations is already providing more accurate chemotherapy dosing for children with leukemia and promises to refine treatment for individuals with asthma.

FDA has championed the shift to personalized medicine as the 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 to determine 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.

Sponsors are exploring protocols for incorporating genomic data into clinical and toxicology studies through FDA's voluntary genomic data submission (VGDS) program. The agency has discussed approximately 50 research plans under the program, has developed guidance for submitting such data, and recently expanded VGDS into VXDS to include additional "'omic" exploratory data.

More cancer drugs are being approved for patient subsets as a result, as well as diagnostics for genomic markers. However, links between tests and treatment has raised questions about the viability of drug-diagnostic co-development. Pharmaceutical and biotech companies are using diagnostics in clinical development 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.

While the shift to targeted medicine may spur development of innovative diagnostics, the trend promises to broadly influence 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 a lower cost with greater likelihood of success. At the same time, there are fears that targeted clinical development may be more expensive and complex. Some experts are skeptical that sponsors will be able to use genetic testing to eliminate non-responsive individuals from trials and note that clinical trial sample sizes may have to be larger to obtain meaningful data on subgroups.

ENSURING SAFETY

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 drugs cause severe reactions in some individuals could prevent the loss of drugs like Vioxx, pointed out George Downing, director of the HHS personalized healthcare initiative at the PMC conference.

Several 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 GlaxoSmithKline, Abbott, 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, SAEC will examine cardiology problems or kidney disease associated with certain medicines.

RATIONALIZING COSTS

A prime objective of health plans, insurers, and pharmacy benefit managers is to use pharmacogenomic data to better inform drug coverage and reimbursement. Current drug pricing models are under considerable pressure, particularly as US consumers face co-pays up to 25% for high-cost biotech therapies, noted Dan Mendelson, president of Avalere Health.

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 Health is assessing whether genetic testing can identify those patients most likely to benefit from the use of tamoxifen to prevent breast cancer or suffer adverse events from taking warfarin. Results may prompt Medco and other PBMs to require testing for patients taking this and similar medications. This, they hope, will reduce wasted spending and steer non-responsive patients to more effective alternative treatments.

Pharmaceutical and biotech companies are looking for 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 the outcomes of a targeted patient population. Business models for personalized medicine will feature smaller, more targeted clinical trials, risk-based pricing, and marketing approaches that emphasize physician education and incorporate diagnostic testing.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, jwechsler@advanstar.com