PGx Labs Concerned by FDA’s Statements, Actions

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

CEO SUMMARY: Since April, the federal Food and Drug Administration 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 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 to a PGx laboratory affiliated with a Virginia health system. In its letter, the FDA warned the lab about “illegally 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 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.

Pharmacogenetic Tests

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 to identify patients with cancer and other diseases who would respond favorably to specific therapeutic drugs.

For many pharmacogenetic tests, the evidence is well established to the point where the FDA has told the makers of some pharmaceuticals to add what are called black box warnings on their drug labels. The warnings state clearly that the drug in question should be taken only after the patient’s physician has reviewed the corresponding pharmacogenetic test results. But for other PGx tests, the evidence is less clear.

Concerns about FDA Actions

All the actions taken by the FDA since April 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. 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 that 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.

FDA’s Opening Salvo in Battle over PGx Tests Was Directed at Inova Genomics Laboratory

IN APRIL, THE FOOD AND DRUG ADMINISTRATION ANNOUNCED THAT IT HAD ISSUED a warning letter to a Virginia lab company that the FDA said was “illegally marketing certain genetic tests that have not been reviewed by the FDA for safety and effectiveness.”

In an announcement on April 4, the agency said it sent a letter to Inova Genomics Laboratory in Falls Church, Va., warning that the lab’s tests claim to predict patients’ responses to specific medications based on genetic variants.

Key passages from this FDA letter allow pathologists and clinical lab administrators to understand how the federal agency describes its concerns with pharmacogenetic testing, which generally are offered as laboratory-developed tests (LDTs).

‘Significant Health Risk’

In its letter to Inova, the FDA said, “Selecting or changing drug treatment in response to the test results could lead to potentially serious health consequences for patients. The FDA is unaware of any data establishing that Inova’s tests can help patients or healthcare 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.”

At the time, the FDA noted that consumers have been embracing genetic testing as a way to understand their individual risks 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,” the agency said.

But the problem for the FDA was how well these tests have been evaluated.

“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, MD, JD, Director of the FDA’s Center for Devices and Radiological Health.

In particular, the FDA was concerned about PGx tests that claim to predict patients’ responses to specific medications when such claims have not been established and are not described in the drug labeling. The FDA continues to warn patients and healthcare professionals that they should not rely on these tests for treatment decisions, Shuren added.

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 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 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.”

FDA Asks ‘All of Us’ to Hold Back PGx Data

ANOTHER INDICATION that the federal Food and Drug Administration (FDA) wants more oversight over pharmacogenetics testing is an action the agency took involving the National Institutes of Health’s (NIH) research program called “All of Us.”

GenomeWeb reported that the FDA asked program officials at All of Us “to only return to participants information on genetic markers that are in FDA-approved drug labeling. The All of Us program plans to report certain clinically actionable genetic markers, including PGx variants, to participants.”

An NIH spokesperson said the program is collaborating with the FDA on an investigational device exemption (IDE) submission, said GenomeWeb. Researchers submit IDEs when they want to incorporate gene sequencing to guide patient care as part of a federally-funded study.

In describing lab industry criticism of the FDA’s actions directed toward pharmacogenetic testing, GenomeWeb said critics “feel the agency is trying to regulate the practice of medicine and control the dissemination of scientific knowledge.”

The news website quoted a PGx expert at an academic institution, saying, “A lot of people in the field are of the opinion that the FDA may have reached too far in terms of trying to regulate the knowledge around PGx.” The expert asked for anonymity to avoid the FDA’s attention.

“Everyone recognizes the FDA has an important role in regulating the claims of a commercial product if [it is] not supported scientifically,” the expert told GenomeWeb. “But, the notion that they [FDA] are the only ones with the ability to say whether something is scientifically supported or not, that’s not even consistent with most of medical knowledge.”

Physicians Can Consult

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 reported.


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