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Guardant Health Begins First Foray Into Early-Stage Cancer With Commercial MRD Test Launch

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NEW YORK – Guardant Health has begun its first commercial testing outside of advanced cancer this month with the launch of Guardant Reveal, a minimal residual disease detection assay that uses the epigenetic technology developed within the company's Lunar program.

With its launch earlier this month, the firm will now be targeting a new population of patients and oncologists as it markets Reveal for the assessment of early-stage colorectal cancer patients after they have had their tumors removed.

The assay, for which Guardant claims a seven-day turnaround time, is intended to detect residual disease after tumor removal and to surveil patients for early signs of recurrence, informing decision-making about adjuvant therapy and providing more sensitive surveillance.

"With this test, clinicians now have an additional tool to evaluate whether a patient with early-stage colorectal cancer is at high risk for recurrence, helping to inform adjuvant treatment after surgery in certain settings, and to detect microscopic recurrence of cancer months earlier than today’s standard of care," Aparna Parikh, a gastrointestinal oncologist at Massachusetts General Hospital said in a statement announcing the Reveal launch.

Reveal's technology combines epigenetic and mutational signals — detecting cancer-associated methylation patterns across a targeted set of genomic sites as well as searching for specific somatic mutations.

In prior studies, Guardant and its collaborators have demonstrated 91 percent sensitivity in detecting cancers using the epigenetic and mutational approach that underlies Reveal. The company is launching the test without having completed a prospective validation, but it is currently in the midst of a study, called COBRA, which is tracking 1,400 Stage II colon cancer patients to evaluate whether using the company's test to guide post-surgery adjuvant treatment decisions offers an improvement over current standard of care.

The firm is also working on a second prospective interventional study in the adjuvant setting with Stand Up 2 Cancer (SU2C), Massachusetts General Hospital, and Dana-Farber Cancer Institute that is taking a similar approach in Stage III patients.

During a call this week discussing the company's 2020 financial results, Guardant CEO Helmy Eltouky estimated the residual disease detection and recurrence monitoring market to be a $15 billion opportunity.

According to Guardant President AmirAli Talasaz, although it's only a few weeks into its Reveal-focused commercial push, the company is already happy with the enthusiasm it is seeing among key opinion leaders and early adopters that it is targeting. The market for Reveal overlaps with the existing customer base for Guardant's advanced cancer therapy selection test Guardant360, which means that many oncologists now encountering the new MRD offering already have a familiarity with the firm.

That said, Guardant CFO Michal Bell added that the company is not expecting to see material revenue from the test in 2021.

"We think it's going to take some time for adoption," Talasaz added. "Multiple conversations need to happen in order for this to get adopted. But we are super pleased with the early reaction of the market to what we put out there."

As it moves forward in this new niche, Guardant faces a slew of new competitors. Tests already on the market for MRD detection include two tissue-informed, personalized methods, marketed by Natera and Inivata.

Although the colorectal cancer patients that Guardant is targeting with its initial commercialization of Reveal most often have substantial tumor tissue available for testing, the company is promoting the fact that its assay does not require tissue as a significant distinguisher from these other technologies – an advantage for future expansion into other cancer types – something that Talasaz said the firm is planning.

"Besides CRC, we have exciting feasibility data in other cancer types like lung and bladder, which gives us confidence that our test will continue to have market-leading performance as we expand … in the near future," he said during the company's earnings call.

According to Eltoukhy, Guardant's leadership expects some parallels with the progression of Guardant360 from an assay validated for and aimed largely at lung cancer to the pan-cancer genotyping tool it is today.

"Given that many physicians are generalists, and they're seeing many other cancer types, we found that that kind of translates into positive perceptions … as we prove out specific cases for utility in other cancer types," he said.

Using the same technology that underlies Reveal, Guardant is also currently working to complete validation of a second assay for colorectal cancer — in this case for screening in the general population.

The company has stated previously that it expects to complete enrollment of a trial, called Eclipse, that it has designed to support a submission for US Food and Drug Administration approval for this additional indication. According to Talasaz, Guardant continued to see robust patient enrollment in the trial throughout the fourth quarter and currently has 150 sites actively recruiting patients.

In this niche, as well, several competitors are also moving forward with closely matched timelines. These include Exact Sciences and Freenome, which are also employing epigenetic approaches.

Anticipating this boom in new non-invasive CRC screening tests, the US Centers for Medicare and Medicaid Services recently issued a preemptive national coverage determination, addressed broadly at blood-based assays for colorectal cancer screening, which provides coverage for Medicare beneficiaries if a test has proven sensitivity greater than or equal to 74 percent and specificity greater than or equal to 90 percent in the detection of colorectal cancer compared to colonoscopy.

Guardant (along with several of its rivals) greeted the news positively, citing its existing retrospective data that already exceed CMS' minimum requirements.

"We released data already in other cohorts where we have what we believe is performance that will meet the standards and the minimum threshold that has been outlined in the NCD for Medicare coverage, and so, I think we're cautiously optimistic that ECLIPSE will be able to read out well above those targets," Eltoukhy said.

"In the meantime, we are laying out the foundations for a commercial channel in the primary care space," he added. That's going to take a considerable investment and we are certainly in the early stages of building out the team, but as soon as the data reads out, we [want to be] ready to go."