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
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
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