On April 4, the U.S. Food and Drug Association (FDA) issued a warning letter to Virginia-based Inova Genomics Laboratory—a division of the Inova Translational Medicine Institute—for illegally marketing its MediMap pharmacogenomics tests that have not been reviewed by the FDA for safety and effectiveness. The tests in question are used to potentially predict patient response to specific medications, identify drugs that may be ineffective, or harmful, and to suggest dosing levels.
According to an announcement issued by the FDA regarding this action, the agency noted “The FDA is unaware of any data establishing that Inova’s tests can help patients or health care providers make appropriate treatment decisions for the listed drugs. The action today reflects the agency’s commitment to monitor the pharmacogenetic test landscape and take action when appropriate to address a significant public health risk.”
According to a statement sent to Clinical OMICs by Inova, the company “promptly responded” to the FDA’s letter and noted that it had been offering the MediMap tests under what it termed “FDA’s policy of enforcement discretion for laboratory developed tests (LDTs), as previously described in the FDA’s publicly available statements and documents.”
The move by the FDA may indicate that it is once again ready to take up more rigorous regulatory oversight of laboratory developed tests (LDTs). In 2015 and 2016 regulators initiated a plan to require that all LDTs would need FDA approval as medical devices, a move that created significant tension between the body and numerous reference labs and hospital-based molecular pathology labs, which regularly used LDTs to help guide patient diagnosis and treatment.
The regulation of LDTs has taken a back burner under the administration of President Trump, but the rapid increase in the use of molecular testing in general, and pharmacogenomic testing in particular, has once again caught the eye of FDA officials.
“Consumers are increasingly embracing genetic testing to better understand their individual risk for developing diseases. With this rise in popularity and availability, we’re also seeing significant activity in the field of pharmacogenetics, which is the process of understanding what, if any, role genetics plays in a patient’s reaction to particular drugs. Without appropriate evaluation to determine whether these tests work, patients are being put at risk—potentially impacting treatment decisions by providing false promise that they will respond well to a certain medicine or keeping them from using therapies that may benefit them,” said Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health, in a press release announcing the action.
The FDA notes that the use of pharmacogenomic testing can be beneficial to patients in some instances, but data needs to be provided to demonstrate the a relationship between the genetic variants tested for and improved drug efficacy. Such information should then be included in a drug’s label in order to justify use of the test. This framework essentially describes the approval of a companion diagnostic or a complementary diagnostic.
According to Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research, the FDA is trying to balance progress in the field with patient safety. “While we are committed to supporting innovation in this area, we will also be vigilant in protecting against the potential risks and are therefore issuing this warning letter to help protect patients and providers from acting on data that has not been demonstrated to promote the safe and effective use of drugs,” she said in a prepared statement.
Inova tests cited in the warning letter include MediMap ADHD, the MediMap Mind, the MediMap Plus, the MediMap Heart, and the MediMap Baby. The FDA first raised its concerns about these tests with Inova in a March 13, conference call with Inova officials and gave the company until March 25 to respond in writing to those concerns.One example noted by the FDA is MediMap’s testing for the liver enzyme CYP2C19 to indicate the prescription of the antidepressant drugs sertraline (Zoloft) and escitalopram (Lexopro). “The relationship between CYP2C19 genotype and drug response to escitalopram and sertraline is not established and this relationship is not described in the FDA-approved labeling for these drugs.
“Healthcare providers may make inappropriate treatment decisions based on these test results,” the letter stated, “including inappropriate dosing adjustments, prescribing an ineffective therapy, and not prescribing a therapy that could benefit the patient. Such inappropriate treatments could lead to immediate serious health consequences for the patient.”
Inova noted that it is compliant with the federal Clinical Laboratory Improvement Amendments (CLIA) requirements, including those requirements applicable to LDTs, as dictated by the Centers for Medicare & Medicaid Services. It added that its Inova Genomics Laboratory is both CLIA-certified and is accredited by the College of American Pathologists (CAP).
Inova has 15 days to formally respond to the official warning letter issued April 4.
This story has been edited to include comments provided by Inova Genomics Laboratory.