PGx Testing Labs Concerned by FDA’s Statements, Actions

Federal agency is telling PGx testing labs to assess if their PGx lab tests comply with regulations

This is a synopsis of two in-depth articles in the Sept. 3, 2019 issue of THE DARK REPORT (TDR). The full articles are available to members of The Dark Intelligence Group.

CEO SUMMARY: Since April, 2019, the federal Food and Drug Administration (FDA) has taken steps that target clinical laboratories that perform pharmacogenetic (PGx) tests. In response to letters from the FDA, some PGx lab companies have stopped reporting data that predicts a patient’s response to certain medications. Some pathologists and lab executives have criticized the FDA’s actions about PGx lab tests as being unclear, confusing, and exceeding its existing regulatory authority.

IN THE BATTLE between the Food and Drug Administration (FDA) and the clinical laboratory industry over regulation of laboratory-developed tests (LDTs), the FDA is taking steps that may change ways in which medical laboratories market pharmacogenetic (PGx) tests.

This latest fight started when the FDA sent a letter in April 2019 to a PGx laboratory affiliated with a Virginia health system. In its letter, the FDA warned the lab about “illegal marketing” associated with some genetic tests it performs.

Later that same month, the FDA issued an announcement and stated it had contacted certain PGx laboratory companies to express concerns about the claims these lab companies were making about how their genetic test results could be used to determine a patient’s response to certain medications.

These two FDA actions were then followed by a series of letters that the FDA sent to PGx labs earlier this summer. In these letters, the FDA asked the labs to interpret its earlier statements about PGx testing from a regulatory perspective.

This raised concerns at the labs receiving these letters because few pharmacogenetic tests have been submitted to the FDA for review and clearance. Most PGx tests are developed and performed as laboratory-developed tests. For this reason, some lab directors and pathologists have interpreted the FDA’s actions as meaning the federal agency seeks to expand its power to regulate LDTs.

Those lab executives and industry experts who have seen these letters and studied the FDA’s announcements about PGx testing have said the federal agency is issuing unclear and confusing guidance and may be overstepping its current regulatory authority.

Until recent weeks, however, only a limited number of pathologists and clinical lab executives were aware of these developments. That changed in mid-August when GenomeWeb and later Stat News reported on the FDA’s actions directed at laboratories performing PGx tests and the reaction to these actions among pathologists and executives at labs that offer PGx tests.

Knowing Which Patients Will Benefit

By way of background, for years, molecular and genetic testing labs have been developing pharmacogenetic tests that physicians use to assess how well patients will respond to certain medications.

In the late 1990s, for example, the FDA cleared a HER2neu test as a companion diagnostic test to determine which breast cancer patients would benefit from the cancer drug Herceptin. Since then, a number of genetic tests have gained clinical acceptance as a tool for identifying patients with cancer and other diseases who would respond favorably to specific therapeutic drugs.

All the actions taken by the FDA since April 2019 caused leaders at many molecular testing labs to become concerned that FDA regulators were suggesting that only the FDA can determine what pharmacogenetic testing information is scientifically valid. Experts in molecular testing dispute this assertion.

Moreover, the FDA’s collective actions targeting PGx tests, and the labs that perform them, have lab directors and pathologists also concerned that the FDA has suddenly begun taking unexplained steps to regulate a field that had not previously been subject to much FDA scrutiny.

These concerns grew after the FDA took actions against labs offering PGx testing without premarket clearance in an attempt to prod those labs to submit their tests for regulatory review, according to reporting by the website GenomeWeb on Aug. 16.

The FDA has not issued a formal statement about its intentions. Therefore, PGx labs are scrambling to decide how the agency expects them to respond. Some PGx testing companies decided that the best response was to report only PGx variants detected in patients’ test results. These labs are removing any mention of drugs or drug classes from their online marketing materials or lab test reports, GenomeWeb reported.

PGx Lab Gets FDA Letter

The first salvo in the FDA’s actions to clamp down on provider organizations that promote PGx testing appears to have come in April 2019. It was on April 4 when the agency announced that it had sent a letter to Inova Genomics Laboratory in Falls Church, Va., warning the lab about “illegally marketing certain genetic tests that have not been reviewed by the FDA for safety and effectiveness.” This lab is affiliated with Inova Health, a five-hospital system.

After it sent the warning letter to Inova, the FDA issued a public statement, saying it “reached out to several firms marketing pharmacogenetic tests with claims to predict how a person will respond to specific medications in cases where the relationship between genetic (DNA) variations and the medication’s effects has not been established.”

Most firms addressed the FDA’s concerns by removing specific medication names from labels, promotional materials, and patient test reports.

In the FDA announcement in April, Janet Woodcock, MD, the Director of the FDA’s Center for Drug Evaluation and Research, said the agency was committed to supporting innovation in the area of PGx testing, and added, “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.”

In recent weeks, the FDA has sent letters to PGx testing labs that reference the warning letter it sent to Inova and asks labs to interpret what the Inova warning letter means for them from a regulatory standpoint, GenomeWeb reported. The FDA letter does not provide specific guidance about what actions, if any, these PGx labs must take to ensure compliance with FDA regulations, the website added.

One executive reportedly told GenomeWeb that the FDA wanted the executive’s lab to determine how the letter would apply to the lab’s PGx test offerings and marketing materials. Lab directors know that FDA actions can have a chilling effect on sales. Therefore, some lab executives might want to consider filing for FDA clearance for any assays the FDA may consider to be lab-developed tests, executives told GenomeWeb.

Unsupported Claims?

Last week Stat News reported that the FDA is concerned that PGx labs are promoting the ability of their tests to predict a patient’s response to drugs with unsupported claims. Doing so could harm patients if patients start, stop, or switch medications inappropriately, Stat News reported.

Reports showed the FDA contacted at least four PGx testing companies: Color, Genomind, Myriad Genetics, and OneOme. In August, Myriad’s stock price fell after it told investors the FDA wanted Myriad to change its pharmacogenetic tests, Stat News reported.

In an e-mail response to questions from THE DARK REPORT, a spokesperson for OneOme said, “OneOme recently removed all medications from our RightMed test and report. This was in response both to customer requests for a gene-focused report, as well as to conversations with FDA.

Physicians who order OneOme’s tests can still consult with OneOme’s pharmacists and doctors, to help them interpret patients’ test results, the spokesperson added.

Color and Genomind offer PGx tests with a physician’s order, and they told Stat they recently changed how they report test results. They made those changes “in response to back-channel conversations with the FDA,” Stat News reported.

A Counterpoint

Opposition to the FDA’s attempts to assert more regulatory authority over pharmacogenetic (PGx) testing is expected, given that executives and investors in PGx lab companies prefer lighter regulation of these tests.

But there is another perspective to consider. Serious concerns are associated with some pharmacogenetic tests and whether physicians have the training and knowledge needed to use this genetic test data appropriately in patient care.

In an interview with THE DARK REPORT, Roger D. Klein, MD, JD, said the FDA is reacting to a lack of understanding among treating physicians about how to use these tests appropriately. “One problem in the area of pharmacogenetic testing is that, in general, physicians have been slow to embrace such testing except in some clearly-defined settings,” stated Klein. “Physicians have been slow to adopt these tests because it’s not been clear what exactly they should do with the information they get from PGx testing.

“Just because a variant shows there’s a potential relationship doesn’t necessarily mean you understand what to do with that information in particular patients,” added Klein, a pathologist, attorney, and expert in precision medicine.

A past advisor to the FDA and other federal regulatory agencies and policy-makers, Klein said one of the problems for laboratories that develop PGx tests is the lack of adequate direction in the clinical literature about how to use these tests.

“That’s because the field of pharmacogenetics is in a nascent stage,” he commented. “In this stage, the medical specialties have not yet embraced pharmacogenetic testing to a significant degree.”

“There are some specific instances where good clinical evidence demonstrates that these PGx tests work and that physicians know what to do with the information,” he explained. “But outside of those few areas, there is limited clinical evidence supporting the use of these tests. Most pharmacogenetic tests in use today are for changes that theoretically affect how patients metabolize drugs.

Uptake in Psychiatry

“One specialty that has been receptive to PGx testing is psychiatry,” explained Klein. “These physicians may use pharmacogenetic tests to identify patients who will respond well to certain medications—such as antidepressants—based on their PGx test results.”

An issue seldom addressed by executives at many PGx labs is the lack of data supporting the utility of identifying genetic markers and the lack of studies demonstrating the results PGx tests provided to physicians and how that information can help them improve patient care.

Has your lab been contacted by the FDA about its PGx testing, and if so, what will your response be? Please share with us in the comments below.


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