NEW YORK (360Dx) – Six years after gaining the rights to a point-of-care diagnostic technology originally developed at Harvard University, Opko Health is readying a regulatory submission for an instrument and a prostate-specific antigen test based on the technology.
If successful, the platform, called Claros 1, could make quantitative immunodiagnostic testing readily accessible to physicians, simplifying testing procedures and increasing testing compliance among patients, a company executive said.
Opko recently announced it had begun a 15-center clinical validation study for the first test slated to run on Claros 1, a proprietary total PSA microfluidic assay. Anticipated to include 1,000 patients, the study would support a premarket approval submission to the US Food and Drug Administration.
Simultaneous with its FDA submission, Opko plans to seek CE marking for the instrument and the PSA test. The premise is to arm physicians with a diagnostic tool that would make it easier for patients to get tested for prostate cancer, Opko Diagnostics President David Okrongly said in an interview.
While total PSA testing has been around for decades, the novelty of the Claros 1 PSA test is that it would be the first instrument to allow doctors to perform PSA testing directly in their offices without the need for a venipuncture, he added.
"You can basically take a finger stick whole blood and get a quantitative PSA result in 10 minutes," Okrongly said, adding that standard total PSA tests takes between 24 and 72 hours for results. "For the first time, a quantitative immunodiagnostic test can be run in a physician's office."
In the US alone, the addressable market for the Claros 1 PSA test would be all men who undergo PSA testing, which Okrongly estimated at between 20 million and 25 million men annually.
PSA testing — and who should actually get the test — has been a source of confusion, but Okrongly said the Claros 1 test could clear up some of the misconceptions.
The United States Preventive Services Task Force advises against PSA screening due to concerns about overdiagnosis and overtreatment. While the risk of getting prostate cancer increases as men get older, the disease develops so slowly that many men diagnosed with it won't actually die from it.
However, cases such as Ben Stiller's muddy the waters. In the fall, the actor revealed that he had been diagnosed with prostate cancer in 2014 and said that the PSA test had saved his life. He further suggested all men over the age of 40 should get tested, which some medical experts called misguided.
But the opposite situation — when men don't get tested, even though their doctors want them to do so — also happens, Okrongly said. Some forego testing, partly due to the inconvenience of having to go to a lab or having to wait for days for the results. When the result does come, it contains little or no explanation about the data, Okrongly added.
By comparison, because the Claros 1 PSA test is done in a doctor's office, it would encourage a dialogue between patients and their doctors, Okrongly said, and would increase the compliance rate of men who, in fact, need to be tested.
In addition, because the Claros 1 test can return results in 10 minutes, a doctor can easily explain those results to the patient and make recommendations during the same visit, he added.
Those whose results indicate they are at no risk for developing prostate cancer would be told to go home, while those identified by the Claros 1 PSA test as being at risk would be referred to reflex testing. Opko also offers its 4Kscore test for identifying men with a high likelihood of developing an aggressive form of prostate cancer, and the company is developing a testosterone test for Claros 1, which would be complementary to PSA testing.
"So, that's our initial focus with Claros — to really outfit urologists, and even primary care physicians who screen for PSA or use testosterone, hormone replacement with their male patients who need it … [with] the tools they need to manage those patients," Okrongly said.
The Claros 1 instrument will cost about $2,500, and will also be available under a reagent rental agreement. The cassettes will cost about $10-$15 per cassette, depending on the test.
The plan is to complete clinical validation studies for the Claros 1 PSA test in the first half of this year, and then to submit the results to the FDA in the second half of the year.
The firm will conduct four clinical studies required by the FDA for approval of a PSA detection test, the claim that Opko is pursuing, at 15 sites across the US. It will not seek regulatory approval of the test for monitoring purposes, however.
The two main studies will each have a cohort of 500 patients. One will be to determine the normal PSA range on the Claros 1 test for a healthy male population age 50 and above. Opko expects its test will show that the 95th percentile of normal will be around 4 nanograms per milliliter, the same as other PSA tests, Okrongly said.
In a parallel study with another 500 men already identified as needing prostate biopsies, Opko will measure PSA levels using the Claros 1 test. Opko will then use the data from the normal-range study to determine the sensitivity and specificity at the 95th percentile of normal of the Claros 1 PSA test in detecting cancer.
Two smaller studies will demonstrate the analytical performance of Opko's test.
Okrongly declined to disclose the names of the 15 sites where the clinical studies are being conducted, but said that Opko will leverage its Bio-Reference Laboratories patient service centers, through which thousands of patients go daily, to offer men age 50 and above the opportunity to participate in the clinical trial.
"That's going to be a big part of our patient accrual," Okrongly said.
If the FDA approves the PSA test and the Claros platform, it would represent a milestone for the technology developed by Harvard professor George Whitesides. The company Claros was founded in 2004 to commercialize the technology, and seven years later it was acquired by Opko.
According to Okrongly, the Claros 1 analyzer is a "basic reader." The breakthrough is in the microfluidic card, which uses a patented detection technology to generate a sensitive signal very quickly by leveraging gold nanoparticle technology. Using whole blood — no separation is performed — the Claros platform quantitatively measures what's in the plasma.
Opko is betting that that quantitative capability will differentiate its instrument from other existing platforms.
Currently, physicians who want to perform immunodiagnostic services performed on their patients can either send a patient to an outside lab such as Bio-Reference, Quest Diagnostics, or Laboratory Corporation of America, or they can purchase an system from Roche or Siemens, which can be large and expensive.
Then a few years back, Theranos exploded onto the scene with a quantitative immunodiagnostic platform technology that seemed potentially capable of changing POC testing. Before the firm cratered under the weight of regulatory actions by the US Food and Drug Administration and the Centers for Medicare and Medicaid Services — and an inability to publicly demonstrate that its technology actually works — Opko viewed Theranos as its main competition to the Claros 1, Okrongly said.
Abbott's iStat and Alere's Triage instruments have quantitative capabilities for cardiac diagnosis, but physician office adoption of those technologies have "not been very successful," according to Okrongly.
Those firms dispute his claim, however.
An Abbott spokesperson did not comment specifically about physician office adoption of the firm's i-STAT platform, but said that in the US, 1 in 3 hospitals use the instrument, and internationally, the company's POC business grew by almost 20 percent in 2016, driven by "greater adoption of i-STAT around the world."
She further noted that a next-generation POC platform, called i-STAT Alinity, which recently received CE marking, "can perform and analyze the largest menu of blood tests on a single, handheld device (ranging from blood chemistries to cardiac markers), using only a few drops of a patient's blood and delivering results within two to 10 minutes.
A spokesperson for Alere said that in the US, the company's Triage platform is mainly marketed to hospitals, but in Europe, Triage sales are "primarily in physician office labs." Alere doesn't disclose sales figures by product line, but the firm's overall revenues are equally split between hospital and physician office lab sales, and Triage is the No. 2 POC platform in the cardiovascular testing space with an installed base of more than 16,000 meters, she added.
As molecular diagnostics move into the point-of-care space, they also could compete with Claros 1, although Okrongly said that Opko and MDx firms differ in their approaches to the POC market. For one thing, molecular POC firms are interested primarily in influenza and other infectious diseases.
"Is infectious disease diagnostics something potentially something we'd be doing? Absolutely, but we would be looking for immunological response," he said, adding immunodiagnostics and molecular diagnostics would be complementary, rather than competing, technologies.
Along with the PSA and testosterone tests, which is also expected to go into clinical trials this year, Opko plans on developing assays for conditions such as cardiac disease, oncology, therapeutic drug monitoring, and the detection of other hormones.
The firm will leverage the Bio-Reference sales force to market Claros 1 tests, so Opko will develop the menu with an eye toward primary care and women's health, as well as cancer, he added.