FDA to Address Advanced Companion Diagnostic Tests

Life Sciences Law & Industry Report connects the dots among the many disciplines that make up the burgeoning life sciences industry, with biweekly updates on current regulatory, legislative,...

By Jeannie Baumann

Sept. 30 — The FDA plans in early 2016 to issue a draft white paper and hold a public hearing on advances in genetic testing that are changing the paradigm for companion diagnostic tests, one of the agency's medical device reviewers said Sept. 30.

Companion diagnostic devices—in vitro diagnostics or imaging tools that provide essential information for the safe and effective use of a corresponding drug or other therapeutic product—historically have been developed under a “a one-test, one indication” paradigm at the Food and Drug Administration, Aaron Schetter said. But the growth of next- generation sequencing tools for oncology has allowed clinicians to increasingly perform “parallel sequencing,” or using a single test panel to evaluate several drug targets and see if a patient is a candidate for several potential drugs at once instead of running individual screens for each drug.

“It can be fast and easy, but this creates regulatory challenges because there are a lot of issues to discuss,” he said.

Schetter is a scientific reviewer in the FDA's Division of Molecular Genetics and Pathology, which oversees companiondiagnostics. The division is part of the Office of In Vitro Diagnostics and Radiological Health in the Center for Devices and Radiological Health. His presentation on recent developments in companion diagnostics was part of a panel on genetic testing at a Drug Information Association conference on companion diagnostics.

Role in Precision Medicine

Due to their ability to evaluate whether or not a single patient will benefit from a particular drug, companion diagnostics have been highlighted in the discussion of targeted treatments for patients (9 LSLR 851, 7/24/15). Advancement of targeted therapies has been getting more attention as the White House, National Institutes of Health and FDA move forward on a $215 million initiative in precision medicine, a medical model that accounts for differences in people’s genes, environment and lifestyle to determine optimal treatment for individual patients.

Jennifer Shen, who is also a scientific reviewer in the same FDA division as Schetter, said the National Academies' 2011 report on precision medicine established a framework for targeted therapies, under which the FDA has been operating for the past four years (5 LSLR 1052, 11/4/11).

“We want to provide better diagnostic tools and improve patient health outcomes,” she said.

23 Approved Companion Diagnostics

To date, Schetter said, the FDA has approved 23 different drug-diagnostic combinations, 22 of which have been for oncology indications. The FDA decides during the drug review process whether there needs to be a companiondiagnostic to administer the drug. While the CDRH provides insight on the device, the current policy for companiondiagnostics is co-approval with the drug by the FDA's Center for Drug Evaluation and Research, he said. “We’re there toprovide insight, but it is a drug review decision that determines whether or not a companion diagnostic is needed.”

The new tests that can screen for multiple analytes, or substances whose chemical constituents are being identified and measured; multiple indications; and multiple drugs are being used increasingly in the clinical setting to guide patient care. But they also create regulatory challenges, Schetter said, including:

• how to establish clinical validity for all of the analytes for a single test,

• how to establish analytical validity when 50 to 100 genes are being sequenced at the same time,

• how to address robustness of the testing across different tissue types and

• whether the single next-generation sequencing assay will be used for all tissue types.

“We've had a lot of internal discussions on this,” he said. Schetter said he hopes the draft white paper and public workshop will provide an opportunity to discuss these issues.

Addressing these challenges will only become more pressing, he said, as the FDA is approving an increasing number of new drugs for targeted therapies. In the early 1990s, he said, 5 percent of new drug approvals were for targeted therapies; in 2013, that percentage jumped to 45 percent. Most of the new drugs—80 percent—that the FDA has approved under its breakthrough designation have been for targeted therapies, Schetter said. Breakthrough status is a new approval pathway created under the 2012 Food and Drug Administration Safety and Innovation Act (Pub. L. No. 112-144) that allows expedited reviews for qualifying new drug applications that treat a serious or life threatening disease or condition.

“With all these targeted therapies approved and in the pipeline, there’s a need to identify the intent-to-treat populations for the different therapies,” he said.

To contact the reporter on this story: Jeannie Baumann in Washington at jbaumann@bna.com

To contact the editor responsible for this story: Randy Kubetin at rkubetin@bna.com

More information on the DIA companion diagnostic conference is available at http://www.diaglobal.org/en/conference-listing/meetings/2015/09/companion-diagnostics.

More information on companion diagnostics is available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm.

The National Academies report is available at http://www.nap.edu/catalog/13284/toward-precision-medicine-building-a-knowledge-network-for-biomedical-research.