NEW YORK (GenomeWeb) – After delays in finalizing its test algorithm and technology platform, OncoCyte said this week that it believes it can launch its non-invasive lung cancer test by the end of this year following strong performance data from its latest internal validation using a population-reflective, blinded sample cohort.
OncoCyte's test, called DetermaVu, algorithmically analyzes a panel of gene expression biomarkers linked to the body's immune response to cancer to determine whether a lung nodule, found either incidentally or via screening programs, is likely or unlikely to be cancer.
The value proposition, according to OncoCyte CEO Bill Annett, is that the implementation of the assay would significantly reduce unnecessary lung biopsies, which in addition to being expensive, have disheartening complication rates.
A study published two weeks ago in JAMA Internal Medicine, for example, examined records from nearly 350,000 individuals who received a lung biopsy and concluded that the complication rate was 22.2 percent for individuals under 65 and up to 24 percent for those in the Medicare age group.
OncoCyte set out to commercialize DetermaVu after licensing IP from the Wistar Institute, and initially expected to have a commercial product on the market by the end of 2017.
But a decision to reevaluate the test platform — at that time NanoString's nCounter — led to a delay in the firm's timeline and then prompted a reexamination of the test signature itself, adding to that delay.
Now the company has emerged with a new platform — Thermo Fisher Scientific's Ion GeneStudio S5 NGS system — a new test signature, and validation results suggesting that the assay should be able to provide 90 percent sensitivity and 75 percent specificity, independent of clinical risk factors.
Although the depth of the company's reconsideration — of both platform and genetic signature — added to the company's commercial timeline, Lyndal Hesterberg, OncoCyte's senior vice president of research and development said that the process was necessary and reflects OncoCyte's attention to making sure that it brought DetermaVu to market with a smooth path toward reimbursement.
Explaining the platform shakeup, Hesterberg said that there had been an initial rationale for sticking with the NanoString technology, because that was what had been initially used at Wistar, when the test approach was first being developed.
"It's a great research tool and it was a logical tech transfer decision to bring that in at the time," he said.
But some challenges in reproducibility at the end of 2017 made it clear that the company should take steps to make sure that there wasn't a more appropriate vehicle for its move to the clinic. During 2018, OncoCyte conducted a "bakeoff" of four platforms, with Ion Torrent emerging as its final choice.
"I can say it has lived up to all of our expectations, and it's really enabled us to achieve the performance we [reported]," Hesterberg added.
Interestingly, the delay that the bakeoff process introduced also opened up an opportunity to reexamine the test biomarker signature in light of new gene expression array products and datasets that hadn't been available when the initial algorithm was developed.
"Once we realized we needed to move the platform, we realized that if we were investing that time and effort why not look at larger expression panels available today," Hesterberg said. "When this was first being explored at Wistar [investigators] were working with Illumina [arrays] of about 11,000 markers," but more recent products allowed analysis of over 40,000 markers, "so why not look and see if there are any that can add value," he added.
During a conference call last year, Annett said that the renewed biomarker discovery effort picked up about 200 additional predictive markers, which the firm has filed patents on. A subset of those have been integrated into the new algorithm, but Hesterberg said that the company is not disclosing the exact makeup of the panel or how it shifted.
Leading up to the validation that the company reported this week, OncoCyte retrained its algorithm using the added biomarkers in 700 samples all run on the Ion Torrent platform.
Starting from scratch with both platform and biomarker discovery may have seemed like a strange move, but Hesterberg argued that the benefits are evident in the performance the company saw with its latest validation.
The company tested this latest rendition of DetermVu in 250 independent, blinded samples, which Hesterberg said were collected specifically to try to reflect as closely as possible the actual clinical population in which the test would be run. The results — 90 percent sensitivity and 75 percent specificity — hew close to what the company was seeing in 2017, but are potentially more powerful because they are now independent of any clinical risk factors.
In the approach to its initial planned launch in late 2017, University of Pennsylvania investigators had reported that OncoCyte's predictive algorithm had 95 percent sensitivity and 73 percent specificity, but only when coupled with clinical information.
Annett stressed that the company believes this will offer a leg up over competitors. The XL2 assay developed by Integrated Diagnostics (which was acquired by Biodesix last year), for example, combines measurement of two plasma proteins — LG3BP and C163A — with pathologic and clinical factors.
Before OncoCyte can begin offering the test clinically, it has to complete three steps to transfer the assay to its CLIA lab, Hesterberg said, including analytical validation of the Ion Torrent sequencer, a small study rerunning samples from the current validation in the CLIA lab to make sure the results are concordant, and then a final validation in another 350 or so samples to confirm a final test performance.
The intention right now is to run the test as an LDT, but OncoCyte has said that the move to Ion Torrent NGS could also allow for development of an IVD kit product for distribution in Europe and other markets in the future.
According to Annett, the firm has already been engaging with payors — ten organizations so far, including Medicare — and all have suggested that the health economic impact that could be achieved with DetermaVu, if used as the company has outlined, seems to merit coverage.
Across the total population who present to a pulmonologist with a lung nodule, whether from screening due to risk factors like smoking, or incidentally when imaging is ordered for some unrelated reason, close to 95 percent of cases are benign, he said.
This presents a diagnostic dilemma: how to find the 5 percent or so who have a malignancy. Doctors "look at size, so if it's over eight millimeters, generally you get sent to biopsy, and if it's between five and eight you generally watch and wait," Annett said. But in that lower size range, there's "no hard and fast rule" and a "not insignificant number of people" still end up having biopsies, he added.
Each biopsy is estimated to cost the healthcare system about $15,000 (including the cost of complications) according to Annett. OncoCyte would expect to price DetermaVu in the "$3,000 to $4,000 range," he said.
The company has said it plans to conduct a clinical utility study after the launch of the test, which will track the anticipated net improvement in patient outcomes and cost savings for the healthcare system, to shore up what it believes the influence of the test could be.
Annett added that OncoCyte believes that the immune-related biomarker content that it has funneled into DetermaVu could also provide improved cancer diagnosis in other tumor types, something the company may explore after this year's launch of its first test.