NEW YORK (GenomeWeb) – Brazil-based Onkos Molecular Diagnostics is interested in entering the US market with its microRNA-based thyroid molecular classifier.
One of the main goals this year at Onkos, a startup located in the University of São Paulo-affiliated Supera Innovation and Technology Park, is to link up with a US lab to commercialize its mir-THYpe thyroid molecular classifier. The real-time PCR gene expression test gauges 11 microRNAs based on a proprietary algorithm and determines whether thyroid nodules are benign and patients can avoid surgery, or if the nodules are likely cancerous and require further workup.
Up to 30 percent of thyroid nodules are deemed indeterminate by fine-needle aspiration (FNA) cytopathology and sent to surgery. But analysis after surgery has shown that as much as 84 percent of the samples turn out benign, meaning that these patients had surgery unnecessarily. Thyroid molecular classifiers such as mir-THYpe aim to reduce the uncertainty for patients whose thyroid nodules cytopathology couldn’t definitively classify and lower the rate of unnecessary surgeries.
However, until Onkos launched its test a year ago, Brazilians had to send samples to the US for analysis. Onkos developed mir-THYpe with the Barretos Cancer Hospital, one of the largest cancer hospitals in Latin America, in order to enable local access to the latest molecular analysis in thyroid cancer assessment.
"We wanted to develop something for Brazil, and be more affordable, local, and develop the test with Brazilian patients," said Onkos Founder Marcos Santos. "We saw an opportunity because you can't find a similar thyroid nodule test outside the US."
Brazilians can currently send samples to the US for analysis by the University of Pittsburgh Medical Center/CBLPath's ThyroSeq test, and until a few months ago, they could also send samples for testing by Afirma's Veracyte test, but this option is no longer available, according to Santos. Sending samples to another country increases the turnaround time, and there is a lot of paperwork, bureaucracy, and taxes involved. "It's a nightmare," Santos said.
All of this additional work to send samples across international borders ends up pushing up the cost of performing the test, making it too pricey for most people in Brazil. Onkos developed mir-THYpe as a more affordable option that at around $1,200, is 70 percent cheaper than the leading tests performed in the US, Santos estimated.
Onkos' test also spares patients from having to endure additional biopsies, which is particularly important for individuals living in cities far from São Paulo. The company decided to develop a test that uses miRNAs, which are more stable than RNA molecules, and analyzes cells from FNA samples smeared on slides used for the initial cytopathology analysis of the patient's thyroid nodules. "That's a big difference between our test and others," Santos said. "We don't need to do a new biopsy."
Ideally, patients would provide all the necessary samples when they come in for the initial evaluation of their thyroid nodule and undergo FNA, so if there is an indeterminate classification from cytology, the samples that will be used for molecular analysis are already collected and patients don't need to come in again.
"It is important to understand that this situation is not the rule," Santos said, noting that while academic medical centers might collect multiple samples in that first visit, most providers don't do this.
It's more common that a patient undergoes the initial FNA, gets an indeterminate result, and needs to come in again for another painful biopsy for the molecular analysis. "In Brazil, we have only one lab offering ThyroSeq. It is in São Paulo city," Santos said. "So, if patients from Manaus, [a city] 5,000 km away, want to perform this test, [they] need to travel to São Paulo [and] perform a new FNA that will be sent to the US."
UPMC/CBLPath's ThyroSeq, which employs next-generation sequencing to gauge DNA and RNA markers in 112 genes, can use samples from the first FNA pass from cytopathology, but can require another FNA to specifically collect samples for molecular analysis. Veracyte's Afirma, which involves microarray analysis of mRNA markers, requires two FNA passes specifically for molecular analysis. Interpace Diagnostics and partner LabCorp sell the ThyGenX NGS panel and 10 miRNA-based ThyraMIR, and require a dedicated FNA for molecular analysis. Rosetta Genomics' GX Reveal analyzes 24 miRNAs by qRT-PCR and can be run using a slide with a smear of the sample collected during cytology.
Onkos' mir-THYpe also uses the cytology slide from a patient’s first biopsy. "In our example, if the patient from Manaus wants to perform [mir-THYpe], he neither has to do a new FNA, nor travel 5,000 km," Santos said. Patients can request their local labs for the smear slides, and can mail them to Onkos in a kit that the company sends to their homes.
Taking a second sample for molecular analysis that wasn't evaluated by a cytopathologist can confound the results, Santos cautioned. The new FNA sample may not have the same heterogeneity observed by cytology when it was deemed indeterminate. "Although it is from the same nodule, the cellularity can be very different," he said.
Additionally, some of the tests mir-THYpe would compete with in the US analyze RNA, which is less stable than miRNA, and requires specialized handling. Using miRNA, therefore, is more advantageous, Santos said, because of its stability and power to differentiate between cancerous and benign thyroid nodules.
While in Latin America, Onkos doesn't have much competition in the commercial sector for mir-THYpe, he acknowledged that the US market for thyroid molecular classifiers is crowded. Still, he believes that the advantages that mir-THYpe offers in terms of sampling, cost, and by analyzing miRNA, will allow Onkos to carve out a position in this space.
In eyeing the US, however, Onkos wants to avoid the complex logistics and costs associated with shepherding samples across international borders, and set up a lab partnership locally that will be able to collect and run the samples and send the raw data over electronically to Onkos for analysis using its algorithm and reporting.
"Our aim is to find a partner with whom we can do a tech transfer," Santos said. "The black box is the algorithm that analyzes the sample, so [the partner] can run the [real-time PCR] test in the US, and send the data to us and we'll classify the samples in Brazil."
In this way, the partners would not be sending samples between countries but sending data. "That's much faster and easier," he said.
In Brazil, mir-THYpe has been available for a year, and Onkos has analyzed samples from patients all over the country. Patients are currently paying for mir-THYpe out of pocket because there is no coverage for the test yet, but Onkos is in the process of finalizing payment codes and beginning discussions with payors.
The company is also conducting studies to demonstrate mir-THYpe capabilities. Onkos recently published the first validation study for mir-THYpe in Thyroid, in which the test is reported to have 95 percent sensitivity, 81 percent specificity, a negative predictive value of 96 percent and a positive predictive value of 76 percent.
Given the rate of indeterminate classifications with gold-standard FNA cytopathology, Santos said the initial validation data for mir-THYpe suggests it has sufficient positive and negative predictive value to be used as a rule-in test for determining potentially cancerous nodules that need surgical follow up, as well as a rule-out test for who can forgo surgery. Onkos is conducting a multi-center, retrospective validation study for mir-THYpe involving 15 hospitals and universities from Brazil, Argentina, Peru, and Mexico, while the Irmandade of Santa Casa de Misericórdia de São Paulo is independently performing a prospective validation of the test.
At the Latin American Thyroid Society Congress in Buenos Aires in June, Onkos will present data from a prospective study on around 100 patients receiving positive results, who end up getting surgery, to assess mir-THYpe's accuracy in predicting which nodules are malignant.
Prospective validation of a test like this is more difficult for those who get negative results, Santos said, because while these patients' outcomes can be tracked in the near term through ultrasound results and nodule growth, they won't get surgery to definitively determine if the molecular test prediction was correct.
While continuing to build the evidence underlying mir-THYpe, Onkos is also broadening its product offerings. Santos said his company aims "to develop molecular tests in oncology to try to solve diagnostic uncertainties and reduce procedures."
Onkos has already developed a test for cancers of unknown primary, called Tumor Origin Test, and licensed it to the Fleury Group, which operates one of the largest lab networks in Brazil. The company is also in the process of validating a test that assesses the risk that a man's prostate cancer will metastasize in five years. Onkos expects to launch the prostate cancer offering, another miRNA based test, in the next 15 months.