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Banner Year for Blood-Based Cancer Screening in 2021, but Reimbursement and Utility Hurdles Loom

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NEW YORK – Just a few years after such tests were considered merely a hypothesis, 2021 saw the first genomic sequencing-based cancer screening assay enter the market, with the launch of Grail's Galleri, a 50-cancer test now available by prescription for patients either willing to self-pay or who are members of a set of early-adopter partner health systems.

Galleri and the other tests hot on its heels have the potential, if implemented more widely, to transform the landscape of cancer diagnosis and treatment, and to upend longstanding patterns of clinical care and medical screening.

Among the companies following closely on Grail's heels are several others targeting multiple tumor types, as well as a variety of disease-specific assays for areas like colorectal and lung cancers, where established screening paradigms offer a smoother road to adoption and reimbursement.

For some of these, 2021 was a year of accelerated recruitment for the pivotal trials that are expected to support US Food and Drug Administration or other local regulatory clearance, while for others it marked a debut, or even just a toe-dip into an increasingly competitive space.

Among the competitors, Guardant Health is developing its early detection technology initially for colorectal cancer screening. The company is poised to follow Grail as the second to bring a sequencing-based early detection test to market, with executives saying in August that they expect to launch within the first half of this year — initially as an LDT but with an expectation of gaining US Food and Drug Administration clearance in 2023.

Guardant has been validating its CRC assay in a prospective trial, which it said had recruited 10,000 patients by last fall out of an expected total of 13,000 to build the required dataset for submission to the FDA.

Freenome, another longstanding player with CRC as its first target, said in October that its own registrational trial had completed data collection for over 22,000 subjects, and that the firm is anticipating a commercial launch in late 2023 or early 2024.

Exact Sciences, maker of the stool-based test Cologuard that has become a prominent tool in colorectal screening, is also developing a blood-based genomic assay. As of last fall, the firm said that its FDA-targeted trial has enrolled nearly 12,000 patients out of a planned 20,000. Results on the blood-based tests should be ready by the first half of 2023.

All three companies stand to benefit from the United States Preventive Services Task Force's recent move to lower the recommended age for average-risk CRC screening to 45, as well as the Centers for Medicare and Medicaid Services' decision in January to preemptively finalize a national coverage determination for blood-based colorectal cancer screening tests meeting certain criteria.

Bluestar Genomics, which launched in 2018, has taken a different tack, targeting pancreatic cancer. Among milestones in 2021, the company received breakthrough designation from the FDA, and raised $70 million.

Natera, currently a provider of noninvasive prenatal testing, transplant rejection diagnostics, and cancer minimal residual disease assays, signed a deal with Aarhus University in November giving it access to database samples and a methylation technology that it plans to combine with its own techniques for colorectal cancer early detection. The firm said it has already completed the initial design for a CRC screening test and is now moving on to validate it. Eventually, the plan would be to expand to a multi-cancer strategy.

And additional players continue to emerge. Notable new entrants to the single-cancer landscape last year included Delfi Diagnostics, which is advancing a machine-learning-driven method that analyzes patterns of cell-free DNA fragmentation to detect the presence of cancer in assumedly healthy individuals.

Unlike Guardant Health and Freenome, Delfi has marked lung cancer as its first target, a tumor type that executives said represents the leading cause of cancer deaths, with the majority of tumors detected at late stages when prognosis is poor.

Like colorectal cancer, lung cancer has established regulatory recommendations for screening, in this case via low-dose CT imaging for high-risk individuals. This offers an easier road toward reimbursement than that faced by multi-cancer assays.

Other new entrants are anticipating targeting multiple tumor types. Precision oncology firm Caris Life Sciences hasn't set a date for a cancer screening test launch, but CEO David Spetzler said last May that the firm intends to develop a variety of blood-based cancer tests using a backbone of whole-exome sequencing of cell-free DNA and cell-free RNA, which would include a cancer early detection application.

According to Spetzler, the firm is validating screening tests for breast and colon cancers initially, hoping to recruit cohorts of about 10,000 patients to build enough data for a clinical launch.

Adela, a spinout from Canada's University Health Network, is commercializing a DNA methylation-based liquid biopsy technology called cfMeDIP-seq that has shown potential for detecting at least 10 different cancer types in early data. Adela closed a $60 million Series A financing round in June of last year.

Guardant, Exact, and Freenome have all cited plans to eventually expand their assays from CRC to additional cancer types. Freenome presented early data in pancreatic cancer last year, but also has ongoing work focused on 16 cancer types, including breast and prostate cancer. In December, the company closed a Series D funding round totaling $300 million, bringing its total financing to over $800 million.

Exact is also continuing to develop CancerSeek, the multi-cancer screening test it brought in with the acquisition of Johns Hopkins spinout Thrive Earlier Detection in 2020. Executives said during the year that 2021 has seen improvements to the test's sensitivity, and future plans include the launch of a pivotal study to support FDA approval in 2022.

In China, Burning Rock Biotech continued to make progress on a pipeline of iteratively broader cancer screening assays during 2021. In November, company executives said that they remain dedicated to a 2022 launch for the firm's six-cancer early detection assay, having signed on six hospital customers.

With the test launched, the company plans to begin a prospective/interventional study in the intended use population in the first half of this year to support regulatory registration for the assay in China.

The firm also expects its first data readouts from a large study of its next-in-line nine-cancer screening assay by the end of this year.

Unlike the cancer-specific settings that companies like Guardant, Freenome, and Exact Sciences are targeting in CRC, or Delfi in lung cancer, multi-cancer screening is an untraveled road.

Modeling studies have estimated that implementing an annual multi-cancer early detection blood test as part of standard-of-care cancer screenings could reduce late-stage (stage III and IV) cancer diagnoses by more than half in the age-50 and older US population — implying an overall reduction of five-year cancer deaths by 26 percent.

But proving clinical utility — showing that the actual impact of tests like Grail's or Thrive's offers a net positive, not just in terms of patient outcomes but also for the healthcare system — will be crucial for driving adoption and payor coverage.

As part of its ongoing studies, and its clinical test provision, Grail is collecting data on test utilization and outcomes that could help allay hesitations around the impact of multi-cancer early detection.

Exact Sciences also said in November that it had partnered with Jefferson Health hospital to survey doctors and patients from diverse populations across the Jefferson health system in order to help determine how to facilitate the implementation of effective multi-cancer early detection testing in the future.

Investigators hope to help determine the impact of MCED testing on a variety of fronts, including health systems, primary care physicians, and patients.

Stakeholders are also awaiting the fate of a bill introduced in the US House of Representatives with a corresponding partner in the Senate called the Medicare Multi-Cancer Early Detection Screening Coverage Act of 2021. The bill proposes to amend title XVIII of the Social Security Act to provide for Medicare coverage of MCED screening tests.

Asked about the legislation, Grail said in an email that without congressional action, Medicare beneficiaries and their doctors will face "significant access restrictions."

"We stand with the bipartisan bill sponsors, and the cancer advocacy community, in supporting this legislation," a company spokesperson wrote.

Both Grail and Exact Sciences are listed as sponsoring lobbying in support of the bill.

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