Skip to content

Pink Sheet – Tissue-Agnostic Cancer Treatments: Can US FDA-Approved Diagnostics Limit Access?

Pink Sheet – Tissue-Agnostic Cancer Treatments: Can US FDA-Approved Diagnostics Limit Access?

Executive Summary

ASCO official argues postmarket development of diagnostics may restrict patient use once added to the label.


Stakeholders are warning the US Food and Drug Administration that slow companion diagnostic development for new tissue-agnostic cancer treatments may raise concerns about patient access.


Richard Schilsky, American Society of Clinical Oncology senior VP and chief medical officer, said approving a companion diagnostic after the treatment could change eligibility criteria seemingly overnight and potentially limit who could receive the drug.


“I have concerns that it could potentially ultimately restrict patient access to a drug that has already been on the market without a companion diagnostic,” Schilsky said during a  workshop on tissue-agnostic and biomarker-based indication development, sponsored by ASCO, FDA, and Friends of Cancer Research.


“If that companion diagnostic is suddenly incorporated in the label as the test that is necessary to select the patient to receive the treatment, there is potentially unintended consequences with respect to our patients who yesterday would have been able to get the drug based on any test, [but] tomorrow [are] only going to be able to get the drug if they’ve had the companion diagnostic test,” he said.


Schilsky told the Pink Sheet after the workshop exchange that he preferred the diagnostics be developed before the therapy is approved. He also did not prefer the tests be called companion diagnostics in labeling, saying they should be added as additional patient selection tools.

Companion diagnostics, as well as lab-developed tests (LDTs), play an important role with tissue-agnostic therapies, as they identify patients with the genetic markers amendable to the treatment. Schilsky was concerned postmarket development was not an efficient use of time, especially since patients would be identified using other tests until the diagnostic is approved.

FDA’s Response: ‘That’s the Paradigm’

Gideon Blumenthal, acting deputy director of FDA’s Office of Hematology and Oncology Products, did not offer much of a reaction to the comment, other than “that’s the paradigm.”


Blumenthal said the agency knows there often are lab-developed tests available and that labeling that includes an approved companion diagnostic will not restrict physicians from using other tests.


“I think it’s sort of a trade-off,” he said. “You want to have some truth. When you approve a drug you want to be able to define your patient population and to have an incumbent companion diagnostic out there enables development of follow-on companion diagnostics and you can sort of compare it to some sort of ground truth.”


The issue may stem in part from historical problems with diagnostic approval at FDA. Products with drug and device components have run into problems because the review timelines often do not sync.


Indeed, FDA already has indicated that it does not want to hold a potentially significant approval any longer than necessary because its diagnostic is not ready.


Leigh Marcus, a medical officer in the OHOP Division of Oncology Products II, told the workshop that the agency made companion diagnostic development a postmarketing requirement so the accelerated approval of Loxo Oncology Inc. and Bayer AG’s Vitrakvi (larotrectinib) was not delayed.


Labeling for the first FDA-approved drug developed prospectively for a tissue-agnostic indication did not specify that patients be identified using an FDA-approved test. (Also see “Vitrakvi, Daurismo Approvals Put US FDA On Brink Of Another Record ” – Pink Sheet, 27 Nov, 2018.)


Lab-developed test (LDT) regulation remains a priority for the FDA. Legislation, as well as agency guidance, are pending, although industry continues to push back on both ideas. (Also see “Unfinished Business: LDT Legislation A Top Priority For Departing FDA Chief Gottlieb” – Medtech Insight, 22 Mar, 2019.)


FDA also discussed the necessary data for the agency to consider a tissue-agnostic indication during the workshop, as well as the use of real-world evidence to add and remove tissue-agnostic indications. (See sidebars.)

Preferred Test Results With Approved CDx?

Josh Bilenker, CEO of Loxo Oncology Inc., said during the workshop that companion diagnostics in labeling also can suggest preference for one drug over another inadvertently.


“In the report, the piece of paper that gets generated when the test comes back, you have a Google Ads problem,” he said. “You now have content which rises to the top because that’s the [companion diagnostic] that’s approved for that drug. There might be two drugs that are equal or one is even better than another, but because this one test is the formal CDx of this one drug, it’s going to pop up that drug as the preferred drug.”


Bilenker also worried that candidates for tissue-agnostic treatments are being missed because the necessary testing is not available. He said that genomic testing must become the standard of care before patients will gain widespread access to the therapies.


“To me the watershed moment is, again, when we start testing everybody,” he said.


Indeed, FDA and stakeholders likely want to get a better handle on the testing issue now that the tissue-agnostic paradigm is becoming more popular. Roche is among those working in the space, developing entrectinib for NTRK gene fusion tumors, as well as a lung-cancer specific indication. (Also see “Pediatric Oncology Advances Could Prompt More FDA-Required Studies” – Pink Sheet, 16 May, 2019.)…