If a group wants to bring a diagnostic to market as a lab-developed test under the FDA’s Clia waiver programme, the regulatory bars are pretty low. This explains why a small validation study of Oncocyte’s DetermaVu gene expression lung cancer test was sufficient to push the group’s shares up 225% yesterday.
“Our test could eliminate up to 75% of unnecessary biopsies,” Oncocyte’s chief executive, William Annett, says. “There haven’t been any tests until now."
Though several liquid biopsy tests are already on sale, these detect cells or DNA shed from solid tumours into the patient’s blood, and the disease must be somewhat advanced before tumour debris reaches detectable levels. Oncocyte’s test detects changes in immune system gene expression levels in response to tumours, and this it says enables the detection of lung cancer at an earlier stage.
Consequently the company contends that DetermaVu will compete not with other liquid biopsies but with the means pulmonologists currently use to determine whether to send a patient for tissue biopsy. This involves a combination of lung X-rays or low-dose CT scans and knowledge of the patient’s symptoms.
Oncocyte declines to state which mRNA markers in particular it is looking at, though Mr Annett says the group’s patent portfolio covers almost 800 different markers, all of them mRNA. The test runs on Thermo Fisher Scientific’s Ion Torrent sequencing system.
Three steps to market
The data reported yesterday look pretty good. Oncocyte says DetermaVu had a sensitivity of 90%, with a 95% confidence interval of 82-95%, and specificity of 75%, with a 95% confidence interval of 68-81%, when used to detect malignancy in 250 blood samples from patients with lung nodules.
“What’s significant about today is that these results show us that we do have a test,” Mr Annett says. “Having said that, there are some steps that we have to go through to get it to market in the second half of the year.”
There are three steps before launch. The first is analytical validation of the performance of the Thermo Fisher next-gen sequencing system, which Lyndal Hesterberg, Oncocyte’s head of R&D, says will be routine, since the Ion Torrent platform is already well established. Second will be Clia validation, in which around 100 of the samples used in the blinded R&D validation are re-run in Oncocyte’s Clia-certified lab to check that they match the earlier results.
“That leads us to the last step, which is to undertake another fully blinded study using prospectively collected samples in the clinical lab itself,” Mr Hesterberg says. “There will be about 350 of these and it’s powered that we get approximately plus or minus 5% on our 95% confidence intervals.”
Data from this trial are expected mid-year. If Oncocyte succeeds it will be able to market DetermaVu as a lab-developed test in the US.
There is a decent health economic argument for the test, if it passes these three evaluations. Lung biopsies have an average cost of around $15,000, according to the American Society for Radiation Oncology, though the median figure is lower. Oncocyte declined to give the price of its test, but claims that chances of gaining reimbursement are high.
The group has had discussions with Medicare and Medicaid and eight private payers, Mr Annett says, seeking their advice on pricing and the needs of the market. According to Mr Annett, “10 out of 10 of them” said that, “subject to them seeing all of our scientific and clinical data, they would be very interested in reimbursement.”
Around 220,000 new diagnoses of lung and bronchus cancer are made each year in the US, according to the CDC. There would certainly be demand for a test costing a few hundred or thousand dollars that could definitively rule malignancy in or out at an early stage when the disease is relatively easily treated. The question is whether DetermaVu is actually good enough to do this.
According to analysts from Chardan, around 26% of diagnostic CTs for lung cancer have indeterminate results, and of these 96% are shown to be false positives. “Hence,” they write, “an accurate confirmatory test, such as Oncocyte’s, could prevent a significant number of unnecessary lung biopsy procedures.”
But it should be remembered that DetermaVu itself has a 25% false-positive rate, according to the validation study. Even if the future trials are successful and the test goes on sale, a quarter of patients given a cancer diagnosis with Oncocyte’s test will still go on to have unnecessary biopsies.
Should the test prove a commercial success the company intends to push it out to Europe and Asia, though getting DetermaVu on sale in the US is its priority.
Moreover, Mr Hesterberg says it is “completely biologically plausible that it can be applied to any of the other solid tumours.” In fact lung cancer is not the first indication Oncocyte has targeted; it has previously worked towards tests in breast and bladder cancers. However, Mr Annett confirms that these are no longer being pursued: “We did some preliminary work in both those areas. Given that we’re a small company we have been very much focused on lung cancer, so we haven’t done anything in those areas in the last year or so.”
Investors in Oncocyte – and those in the biotech group Biotime, which owns a 37% stake in Oncocyte and which saw its own shares jump 55% yesterday – will be hoping that this allocation of resources is justified by DetermaVu’s clinical and commercial performance.