Guardant Health’s Shield, a liquid biopsy that screens for colorectal cancer by analyzing a patient blood sample, will compete against stool-based tests already established in the market. Shield could also face new competition from other liquid biopsy companies.

By Frank Vinluan

FDA approval of a Guardant Health blood test that screens for colorectal cancer makes it the first liquid biopsy approved for this type of cancer, clearing the way to make this test more accessible to more people. But commercialization will be a challenge as the new test is not expected to become the first or even second screening option for patients.

The approval announced Monday for the test, named Shield, covers the screening of adults age 45 and older at average risk for colorectal cancer. Colorectal cancer is the third most common type of cancer in the U.S., excluding skin cancers, according to the American Cancer Society. For men and women combined, it’s the second-most common cause of cancer deaths.

Colorectal cancer is treatable when detected early, but about one-third of the U.S. population is not up to date on screening. Colonoscopies are the first screening option, but many patients choose not to undergo the invasive procedure. At-home tests kits, which give patients a way to collect a stool sample and send it to a lab for analysis, offer a less invasive alternative. In 2014, FDA approval of Cologuard made that Exact Sciences product the first non-invasive test for detecting cancer DNA in a stool sample. The Madison, Wisconsin-based company reported $1.8 billion in 2023 screening revenue, a more than 30.8% increase compared to 2022. While the revenue figure includes tests and lab services outside of Cologuard, Exact Sciences attributes the revenue rise mainly to the increase in completed Cologuard tests.

A liquid biopsy detects signs of a cancer in a small sample of blood drawn from a patient. Palo Alto, California-based Guardant developed Shield to detect signals of colorectal cancer, including DNA shed by tumors. A positive test result from Shield must be confirmed with a colonoscopy. Shield has been commercially available since 2022 as a laboratory developed test. But FDA approval is key for convincing payers to reimburse a screening test. Guardant applied for FDA approval last year. In May, an FDA advisory committee voted in favor of Shield on questions regarding safety and efficacy.

The FDA’s affirmative decision for Shield is based on data from a study that enrolled more than 20,000 average-risk adults at more than 200 clinical trial sites across the U.S. Results showed the test demonstrated 87.5% sensitivity for detecting colorectal cancer at stages I, II, or III. But its sensitivity for detecting lesions that could become cancerous was much lower at 13.2%. The test’s false positive rate was 10%; the false negative rate was 17%. Study results were published in March in the New England Journal of Medicine.

Leerink Partners estimates the colorectal screening market is about $20 billion. In a note sent to investors, Leerink analyst Puneet Souda said physicians will continue to lead this market, which means colonoscopy will remain the de facto first-line screening option. For non-invasive options, Exact Sciences’ Cologuard will lead, given its stronger performance in advanced adenoma and early colorectal cancer, Souda said. Next in line are Shield and fecal immunochemical tests, at-home tests that screen for colorectal cancer by detecting blood in stool samples. Exact Sciences has a next-generation version of its test, Cologuard Plus, under FDA review. A regulatory decision is expected later this year.

“We see clinical providers still choosing the screening modality with most clinical evidence with colonoscopy being first, followed by Cologuard (likely Cologuard Plus next year) and then liquid biopsy options such as Shield,” Souda wrote. “Still, Shield can address a number of unscreened individuals (with a blood draw) for those not willing or unable to perform a colonoscopy or take a stool test.”

By Shankar Srinivasan, Co-Founder and General Manager, GetInsured and Jason Sparks, VP, of Project Management and Implementation, GetInsured

Under a Centers for Medicare and Medicaid Services national coverage determination, Shield meets requirements for Medicare coverage following its FDA approval. Souda said inclusion in updated American Cancer Society guidelines would mandate commercial coverage in certain states. The United States Preventative Services Task Force is the key guideline group for commercial coverage, and Guardant expects an update to these guidelines in 2026.

Other liquid biopsies pose competitive threats to Shield. Grail, which last month spun off from Illumina as a standalone, publicly traded company, has commercialized a multi-cancer early detection test named Galleri. This liquid biopsy screens for more than 50 types of cancer, including colorectal cancer. But Grail commercially launched the test in 2021 as a laboratory developed test. The company has said securing FDA approval is part of a longer-term strategy to broaden payer coverage and reimbursement of Galleri. Freenome poses additional potential competition. In April, the privately held company reported positive preliminary data for its colorectal cancer liquid biopsy, which is being evaluated in a study enrolling more than 48,000 participants.

William Blair analyst Andrew Brackmann said in a research note that Shield’s commercialization hurdles include overcoming pushback from clinicians on the test’s performance and securing reimbursement from payers. Meanwhile, Exact Sciences could also soon compete with Shield in liquid biopsy. The company entered this space via the 2021 acquisition of Thrive Earlier Detection. Exact Sciences is expected to post data this fall for its blood-based test, Brackmann said. If the company succeeds in bringing this test to the market, it could set a price below competitors in a liquid biopsy “blood war.”

“We believe these battles will ultimately be good for the market, but more importantly, patients — providing a large percentage of the population another option and for these blood-tests to likely be targeted/used in different patient groups than more effective solutions like Cologuard,” Brackmann wrote.

Photo: Business Wire