NEW YORK – Following OncoCyte's announcement last week that it is acquiring a portion of Razor Genomics, the company shared plans to help shepherd Razor's lung cancer prognostic assay through additional validation, help the test being adopted by guidelines and integrated into the clinical care of early lung cancer patients, and fully acquire Razor.
Razor, which received a draft local coverage determination for the assay from Medicare contractor Palmetto GBA in August, had previously released little information about its history or strategy. OncoCyte confirmed that Razor is a resurrection of a prior company, Pinpoint Genomics, and that its current test is the "Pervenio" assay that Pinpoint initially developed before being acquired by Life Technologies in 2012.
At that time, Pinpoint already believed it could start reimbursement discussions with payors, and by 2013, Life Technologies had begun offering the Pervenio test through its Sacramento, California CLIA lab.
But when Life Tech was acquired by Thermo Fisher Scientific in 2014, a decision was made to cease offering the test commercially and release ownership back to its developers at Pinpoint — University of California San Francisco surgeons David Jablons and Michael Mann — OncoCyte CFO Mitch Levine explained.
"When Thermo went through their inventory of new products [after acquiring Life Tech], this is one that did not work because it tied them to the patient directly, [at a time when they were] sticking more to the industrial as opposed to commercial products for patients," Levine said. "At that time, [current OncoCyte CEO Ronnie Andrews] was the president of Life Technologies and [he] arranged for the test to be restored to what was known as Pinpoint Genomics at that time and which then became Razor."
"He knew, as [the test developers] knew, that this is a lifesaver and to let it sit on the shelf was a mistake. So they got the test back in I think sometime in 2016 … and they've continued to develop it."
According to Levine, the test's lengthy path back to commercialization reflects the fact that the two doctors then took on further clinical development and validation of the assay through their own Brisbane, California CLIA lab, leading to Razor's recent Medicare coverage recommendation. The test has not been launched commercially yet by Razor but that transition will now take place under OncoCyte.
"These guys are physicians at UC San Francisco and so they've run this test on all of their patients, but they've never put it out for commercialization," Levine said. "But now that OncoCyte is the owner of the test, we will begin commercialization either late this year or early next year."
In a conference call last week discussing the company's acquisition plans, OncoCyte CEO Ronnie Andrews predicted that the recent Palmetto draft LCD will be finalized by early next year. Anticipating that, the firm is planning a soft launch for the Razor assay in Q4 with a full market launch in Q1 2020.
The original validation of what was then called the Pervenio test took place in a set of lung cancer cohorts from Kaiser Permanente Northern California and with hospitals from the China Clinical Trials Consortium. The resulting studies, published in The Lancet in 2012, demonstrated that the 14-gene expression test "reliably identified" early-stage, non-squamous, non-small cell lung cancer patients at heightened risk of succumbing to their disease in the years after they'd had a tumor surgically removed.
But as of 2013, the evidence on the test wasn't yet sufficient for Medicare to agree to cover it through the Palmetto MolDx program.
Since the test moved to Life Tech and was jettisoned by Thermo Fisher, Jablons and Mann have completed additional trials of its validity and health economic impact — most significantly a study published in 2018 in the journal Clinical Lung Cancer, which OncoCyte said provided the backbone for Palmetto's recent pivot to endorse the assay for coverage.
In the study, investigators used Razor's assay to prospectively stratify risk in 100 consecutive patients with stage IA, IB, and IIA nonsquamous NSCLC.
According to the authors, forty-eight of the 100 patients were deemed high risk based on the genomic test, though only 36 of these met current NCCN high-risk criteria. And when they followed patients for several years, comparing their treatment and outcomes to their initial test status, the investigators estimated that those who tested as high risk and who got chemotherapy had a significantly better chance of surviving five years without a disease recurrence than those who tested as high risk and didn't get adjuvant chemo.
The estimated 5-year disease-free survival rate for molecular high-risk patients who did not get adjuvant chemotherapy was about 49 percent, compared to 92 percent in those who did have treatment. For molecular low-risk patients, 94 survived 5 years even without added chemo.
In contrast, five-year DFS was only about 75 percent for the untreated NCCN low-risk patients.
During OncoCyte's conference call last week, Andrews said that the company believes the Razor test is in a position to serve the lung cancer community in a similar way to Genomic Health's Oncotype DX test in breast cancer.
"Oncotype DX has the exact same endpoint in breast cancer that our Razor test has in lung cancer, and today that test is reimbursed around $3,500 dollars and has been since it got its first coverage decision over 10 years ago," he said on the call.
"We believe that having the same endpoint in lung can be very, very powerful for us as a company as we grow revenues and build market value," he added.
The Razor test uses a standard workflow that Andrews said runs on Thermo Fisher's QuantStudio real-time PCR instrument, which already has a large installed base.
As such, while OncoCyte is currently focused on launching the test as an LDT in the US, it believes it could also have an opportunity in the future to create a kitted version of the assay, which it could sell through a channel partner in Europe's more decentralized lab markets.
Andrews also said that OncoCyte is solidifying plans to begin a new international randomized clinical study that it hopes will support international guideline inclusion for the test and help cement its position as a first mover in the space — similar to what Genomic Health achieved with its TAILORx study in breast cancer.
“Long term, in order to solidify utility … you need a randomized trial. And so while we don't need this trial to compete — for us to go to market and start launching — nor to get reimbursed, we think long term, it'll set a huge bar for anyone that might want to come behind us,” Andrews said.
A side benefit of beginning this new prospective study, Andrews added, will also be the opportunity to seek out potential pharmaceutical partners interested in studying immuno-oncology drugs in the lung cancer adjuvant space as part of the trial.
Although no genomic assays are currently marketed for aiding adjuvant therapy decisions in patients with early-stage lung cancer post-surgery, OncoCyte is not necessarily the only mover in the space.
Myriad Genetics for some time was advancing a prognostic assay for this purpose called MyPlan Lung. However, the firm has not discussed its plans in that area for several years and information on the assay is largely absent from the company's website.
Padma Sundar, OncoCyte's senior vice president of marketing, argued that a fundamental difference between the Razor test and Myriad's offering is that Razor, and now OncoCyte, intend to prove that the assay is not just prognostic of disease outcome but predictive of adjuvant therapy benefit. Establishing this definitively will be one goal of the soon-to-begin randomized trial.
According to Andrews, because recurrence in lung cancer happens faster than in breast cancer, the trial should hopefully be able to read out within four years or so.
With plans for the Razor test now defined, Andrews stressed that the acquisition will not alter OncoCyte's recently stated plans for its own DetermaVu assay, which it sees as a direct complement to the Razor test once both are on the market.
When implemented clinically, DetermaVu — designed to noninvasively identify which lung nodules are cancer and which are more likely to be benign — will drive patients who test positive toward surgery. Some of these surgeries will be curative, Sundar explained. But the Razor test can then be performed in the same group of patients to identify the subset who are at high risk of not being cured by surgery alone, and who the company's data suggests can improve their survival prospects considerably by undergoing adjuvant chemotherapy.
In OncoCyte's most recent update on DetermaVu this August, Andrews said that the firm had a few tasks to complete to prepare its final CLIA test validation. As of last week, the company has now completed those final steps — finalizing its extraction reagent and sequestering the lots it will need — and will now "very shortly be moving into the CLIA validation stage," he said.