The role of pharmacogenomic testing in precision medicine

Targeted testing — when evidence-based — has tremendous potential to help improve clinical outcomes, but it is critical to balance use and cost.

We hear much about the promise of genetics as a way to personalize medicine and improve outcomes for people with, or at risk for, serious illnesses. It’s true that our understanding of genetics and the role of things like biomarkers and gene variability have given us new insights into how certain conditions present themselves — and how people respond to treatments differently. Precision medicine guided by genetic testing can be an indispensable tool in identifying the most effective treatment for conditions where therapies are increasingly targeted to specific gene defects or mutations. However, there are many conditions — even those with a known genetic component — where the clinical evidence has repeatedly failed to show a cost-effective benefit in using broad-based genetic testing to guide treatment options.

Where precision medicine can make an impact

Gene mutations — somatic or germline — can lead to someone developing, or having a predisposition to develop diseases like cancer, as well as inherited conditions, including cystic fibrosis, spinal muscular atrophy, Duchenne muscular dystrophy, hereditary angioedema, and growth hormone disorders. Genetic testing can help guide targeted therapy in such conditions and also identify faulty genes that can be treated with gene therapy. This is not only supported by robust clinical evidence, but is actually necessary to ensure that the selected treatment will be effective and efficacious for that person.

Since therapies for these conditions are generally very expensive, administering them to a patient for whom a treatment may not work is wasteful. It can also result in poor patient outcomes, including adverse events, side effects, or worsening or progression of their condition — all of which could lead to even greater waste.

But there has also been a proliferation of unproven pharmacogenomic tests that are not supported by clinical evidence. There can be significant variability to drug response among individuals. In addition to their genetic makeup, drug response might be affected by factors such as age, gender, weight, disease state (e.g., hepatic or renal disease), race, and ethnicity. Pharmacogenomics is the branch of genetics that studies the ways in which an individual's unique genetic makeup influences the response to medications. Pharmacogenetic-based variation can influence either the pharmacokinetic properties of the drug in an individual — such as the rate of absorption, distribution, metabolism, or elimination — or pharmacodynamic properties — such as how well a drug binds to a receptor site thus making the drug available in each individual.

In theory, the identification of genetic factors that influence drug metabolism allows for personalization of drug therapy, increasing the likelihood of drug efficacy and minimizing the toxicity profile based on knowledge of each individual’s genetic makeup. However, a significant body of research of broad pharmacogenomic testing has repeatedly failed to show a clinical benefit in using broad-based testing to determine treatment for conditions such as depression on the basis of such pharmacogenomic variations. In such instances, currently available clinical evidence does not support the cost-effectiveness of broad-based testing because the results cannot aid in identifying the most effective treatment.

Real-life value of precision medicine for specialty pharmacy

At CVS Health, we take — and recommend — an evidence-based approach to guide the use of personalized precision medicine. Caring for complex, specialty conditions should always be driven by the most effective and clinically rigorous treatment available. Not only because it’s the right thing to do, but because it also reduces waste and lowers costs.

We use and promote the use of genetic testing for treatments where it can lead to the most precise, appropriate treatment regimes, like in oncology, because evidence shows that treatment response can be linked to genetic markers, thereby avoiding wasteful spend and risking patient health with less effective treatments.

Our Transform Oncology Care Program, uses the results of broad-panel gene sequencing tests and the latest National Comprehensive Cancer Network (NCCN) Treatment and Supportive Care Guidelines to help providers select the most precise, appropriate treatment regimen based on the patient’s clinical and genetic profile. This ensures that patients get the most appropriate care and reduces waste on treatments that are unlikely to be effective, lowering overall costs.

In addition, for therapy classes where the FDA has recommended incorporating required testing recommendations into drug labels, we incorporate those requirements into our specialty guideline management (SGM) criteria. Test results and appropriate documentation are required at the time of submitting a prior authorization (PA) request for specific indications and diagnosis for more than 160 treatments.

Monitoring precision medicine developments

Not all pharmacogenomic testing is clinically validated and equally relevant in clinical decision making. At the same time, a large number of biomarkers included in drug labeling in cancer prescribing have been validated and incorporated into clinical care. This is as it should be because it has a clear cost and clinical benefit. But further research is required before broad-based testing for variations including the impact of pharmacogenomics in pharmacokinetics are demonstrated to have clinical effectiveness, which is key to deriving value for patients and the health care system.

At CVS Health, we constantly monitor new developments in precision medicine to ensure that patients and payors can take advantage of promising innovations in care that make a real difference in outcomes, cost and value. Our recommended approach is to prioritize the use of validated biomarkers for targeted therapies as supported by the published, peer-reviewed literature, and guidance from medical professionals and health agencies. We believe the future role of pharmacogenomic testing in precision medicine testing warrants further exploration. We will continue to monitor the science and economics to identify and make available testing modalities that bring value to our clients and put members on their path to better health.