By Aaron Krol
September 25, 2015 | This Thursday, the FDA publicly posted a letter to Pathway Genomics of San Diego, Calif., expressing strong concern about a test the company recently launched called CancerIntercept Detect. The test, a “liquid biopsy” that looks for genetic markers of cancer in raw blood samples, is sold as a non-invasive way to look for early signs of cancer in healthy individuals who have a family history of the disease.
When the test was first released earlier this month, many observers were skeptical that this was a reasonable indication for genetic testing, or that Pathway had properly vetted the test before offering it for sale. Arielle Duhaime-Ross of The Verge, after speaking with both the CEO and Chief Medical Officer of Pathway, concluded that “the company itself doesn’t know if its claims are true,” noting that Pathway has not run any long-term studies to learn whether patients diagnosed with cancer by CancerIntercept Detect or other liquid biopsies actually go on to develop the disease. (In our own coverage at Diagnostics World, we observed only that the test was “likely to be controversial” for targeting healthy patients.)
The FDA, which did not review the test before its launch, clearly agrees with that assessment. “We believe you are offering a high risk test that has not received adequate clinical validation and may harm the public health,” the agency wrote in its letter to Pathway. If test results are inaccurate, the FDA worries, healthy users could seek out risky interventions to fight early-stage cancer they may not actually have ― or conversely, patients who do have undetected cancer may get false reassurances, possibly delaying treatment.
To industry insiders, this letter will be instantly reminiscent of the one that the FDA sent to 23andMe, a consumer genetics company based in Mountain View, Calif., in November 2013. Like Pathway, 23andMe was selling a test to healthy individuals, based on genetic correlations, without strict clinical validation, and outside of FDA oversight. And just like in the letter to Pathway, the FDA’s biggest concern about 23andMe was harm to patients who seek medical interventions based on faulty genetic information.
In 2013, the result was a rapid and complete shutdown of 23andMe’s health-related reports to customers and a decisive shakeup of the industry ― although 23andMe itself has thrived in the years since, and is even preparing to release a new, FDA-cleared test later this year. (See, “What Comes Next for Direct-to-Consumer Genetics?”)
If you’re wondering how these companies manage to release these tests without clearing them with the FDA in the first place, the answer is that the exact scope of the agency’s jurisdiction in genetics is still up in the air. Two years ago, 23andMe felt that its health reports were not medical tests subject to FDA review, because they did not diagnose specific diseases. Today, Pathway Genomics is confident that CancerIntercept Detect is a “laboratory developed test” (LDT): a category of test, designed and performed by a single, certified laboratory, that has traditionally been exempt from FDA scrutiny.
Almost all genetic tests offered in the U.S. today are LDTs. Most are performed in the kinds of academic and hospital settings for which the exemption was originally written, but for-profit companies like Pathway are also increasingly running their business out of labs with the appropriate certifications.
Which is exactly what makes Thursday’s letter so interesting. This is about much more than one test tottering on shaky evidence. (In fact, to many oncologists, liquid biopsies are an exciting new technology for early detection of cancer and monitoring of the disease during treatment, and the best possible outcome here would be for Pathway to produce robust clinical validation of CancerIntercept Detect.) The FDA is asserting its right to regulate Pathway and other companies like it, and there are many more test providers who could be affected by the outcome.
It is unclear just what tools for enforcement the agency has at its disposal. In 2013, the FDA told 23andMe to “immediately discontinue marketing” its health reports; today, it’s only requesting a meeting with Pathway’s management. And while the FDA is already in the process of revisiting the LDT exemption, it doesn’t plan to start mandating reviews of these tests until 12 months after a forthcoming “final framework guidance” on the issue is published. Industry groups are strenuously fighting the proposed measures in that guidance, and it is still possible that legal challenges or Congressional action will keep all LDTs outside the FDA’s purview.
In the case of CancerIntercept Detect, however, the FDA may have another option than to wait for its new process to roll out. In its letter to Pathway, the agency stated, “It appears that you are offering CancerIntercept Detect under a direct-to-consumer type model.” That’s a significant statement, because LDTs can only be ordered by physicians, not sold directly to patients.
Pathway, like a spate of other genetic testing companies, has found a creative way to get around this restriction over the past six months. Customers can go to Pathway’s website and request a test, and even pay for it out of pocket, but that request will then pass to a doctor for approval: either the customer’s own primary physician, or one provided by the company. Pathway’s doctors could in theory decide that a test is not a good fit for a particular patient and decline to order it, although it’s unclear whether this ever happens in practice. (For more on this sales strategy and the company, Color Genomics, that pioneered it, see “A Colorful Business.”)
In labeling CancerIntercept Detect a direct-to-consumer test, the FDA seems to have decided that this workaround is not going to fly. Asked for comment on its enforcement options, the FDA provided Diagnostics World with the following statement:
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Although FDA has generally exercised enforcement discretion over laboratory-developed tests (LDTs), it has not exercised enforcement discretion for direct-to-consumer tests even when those tests meet the definition of an LDT. Like 23andMe, Pathway Genomics appears to be offering a direct-to-consumer test. If so, that test would not fall within the LDT enforcement-discretion policy. In addition, FDA is interested in learning more about the role of the blood collection devices used with the Pathway Genomics test.
Typically, a letter that an issue has come to the attention of the Agency is followed by discussion between the industry sponsor and the FDA on the issues put forth. Pathway has stated publicly that they plan to have such a discussion with the Agency. As noted in its letter, FDA has concerns about the apparent lack of evidence to support the clinical validity of this high-risk test. |
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Pathway Genomics, which received the FDA letter three days before it was made public, is not currently speaking to the press about the issue, but it has posted a brief acknowledgement on its blog.
“Pathway Genomics greatly respects and shares the FDA’s concerns about patient safety,” the company wrote, before adding that it believes CancerIntercept Detect to be a laboratory developed test and that its sales model is not direct-to-consumer.