Pharmacogenetic testing for guiding prescription of biologic medications? Myths vs realityRuslan Dorfman, PhD, MBA
The escalating cost of biologic medications has private and public plan sponsors concerned. Many are turning to new technologies to stratify patient populations with the aim of reducing the total cost of biologics. Some providers are considering pharmacogenetic tests to guide selection of drug therapy. Others are looking at substituting branded biologics with biosimilars. A Biosimilar, or “generic biologic”, is a biopharmaceutical drug designed to have active properties similar to a branded biological medicine.
Since biological medications are used to treat complex conditions, such as autoimmune diseases and cancer, a careful selection of candidate patients can improve efficacy and cost efficiency. In oncology, biologics are designed to block activity of specific gene mutations which drive cancer growth. For this reason, a companion test at the time of tumor biopsy (performed by special pathology laboratories) is used to determine candidates for biological medications.
Autoimmune conditions are triggered by a complex interaction of hundreds of different genes. At present, there are no companion diagnostic tests that could be used for patient targeting – i.e. selection of potential responders – for biological medications used to treat MS, arthritis, psoriasis and other inflammatory conditions. Although the PharmGKB database has references to hundreds of markers associated with response to biological medications, these markers or even multiplexed combinations of PGx markers cannot be used for targeting patients due to poor specificity and sensitivity of such tests , . Pharmacogenetic tests that combine pharmacodynamic markers require validation in large scale prospective clinical trials to assess whether such tests can improve treatment efficacy for autoimmune diseases. Use of non-validated PGx tests to select treatment can pose risks for patients with autoimmune disease as treatment failure leads to disability.
In contrast, PGx tests for non-biologic medications are more robust because they are built on direct correlations of drug concentration in the blood and pharmacokinetic gene variations. Use of such tests have shown to improve safety of treatment. For biological drugs, at present, only highly specialized tests built on the gene expression profiling principles from blood samples and aimed at monitoring clinical response to some biologics have reached the required level of clinical validity. For example, the Vectra DA test offered by Myriad Genetics helps physicians characterize disease activity in patients, assess response to treatment, and assess risk of joint damage. Vectra DA can potentially guide second line treatment after methotrexate and inform biologic tapering decisions for patients in stable remission. Such a test would be applicable for both branded biologics and biosimilars.
Antibody titer tests are currently available for therapeutic monitoring of infused monoclonal antibody levels, which are the active form of a biologic medication. These tests have been developed primarily to test how frequently the patient should be re-infused. However, such tests may be specific to a branded drug manufacturer and may require re-validation for biosimilars. Regulatory approval of biosimilars requires demonstration of therapeutic equivalence, ; therefore, they can be readily used to reduce the cost of biologics for autoimmune conditions. Cost reduction strategies based on predictive pharmacodynamic markers are still a “wish” and should not be used until supporting clinical data is validated by independent studies.