NEW YORK – ProciseDx recently received CE marking for a point-of-care instrument, laying a foundation for the launch of a portfolio of rapid tests in physician offices, retail clinics, and urgent care settings that are mostly unavailable for these near-patient markets.
The CE designation came after the firm's decision to lock down the design of the instrument it had been developing for three years and on which it intends to launch assays for use in diagnosing and treatment monitoring of inflammatory conditions, such as inflammatory bowel disease; autoimmune conditions, such as celiac disease; and metabolic syndromes, such as diabetes and pre-diabetes.
San Diego-based ProciseDx was spun off from Prometheus Laboratories, a subsidiary of Nestlé Health Science, though ProciseDx itself remains part of the Swiss diversified products firm.
Prometheus was divested following a review of its global business portfolio to assure continued alignment of Nestlé's top strategic priorities, ProciseDx President Peter Westlake said in an interview.
"Nestlé sees consumer healthcare as an area of growth," he said. "ProciseDx’s point-of-care platform is closer to the consumer than the Prometheus CLIA lab business."
He added that Nestlé Health Science is now looking for commercial, strategic, and investment opportunities for ProciseDx.
ProciseDx anticipates launching its platform in Europe next year with its first test for C-reactive protein, a marker of inflammation and infection, in parallel with a marker for a second undisclosed condition.
Though it is owned by Nestlé, this month the firm anticipates approaching private investors for the first time to obtain up to $20 million to support the development and launch of tests on its shoebox-size instrument, which uses a technology called fluorescent resonant energy transfer (FRET) for analysis. The funding would enable it to expand its assay menu in the US and Europe, and target testing at the point of care for conditions that are available only in laboratories, Westlake said.
The firm is conducting clinical trials in the US in preparation for applying for 510(k) clearance with the US Food and Drug Administration for its instrument and its first assay in the first quarter of 2020. Similar to the product it expects to launch in Europe, the instrument when launched in the US will test for C-reactive protein and the same additional biomarker, Westlake said.
ProciseDx has specifically designed its instrument so that it could be CLIA waived, enabling its marketing in physician offices and other point-of-care settings, and it intends to apply for a CLIA waiver subsequent to applying for clearance through the FDA's 510(k) pathway, he said. The instrument uses established chemistry that consists of proprietary compounds to enable rapid and quantitative results, and it can operate using a variety of specimen types, including finger prick whole blood, venous blood, serum, plasma, urine, saliva, and stool samples.
The instrument's FRET technology transmits light from an excited fluorophore to a light-absorbing molecule — in this case a disease marker with an attached antibody. "When the light shines on whole blood, everything lights up," including the analytes you want to detect and other sample components you don't want to detect, Westlake said.
The system waits until light fades from uninteresting components of the specimen and then detects light from the analyte of interest, enabling the instrument to measure the appropriate marker. The test's chemistry ensures the analyte "emits light for a long time after it has been excited," Westlake said.
He noted that the operating principle of the instrument remains unchanged when new tests are added, but the firm alters the reporter antibodies that emit light and tailors them to specific medical conditions.
FRET technology is not new, but ProciseDx has refined it so that it can be applied for the first time to POC diagnostic testing, Westlake said. "A number of practical problems needed solving that had prevented the technology from being commercialized in this way before," he said. The firm resolved the previous problems associated with ensuring that the system delivers the correct amount of light, for example, and by adding software to optimize its analysis capabilities.
The firm intends to market the test for CRP — a protein made by the liver and sent into the bloodstream — to physicians interested in using it to measure inflammation and infection.
In the European Union, physicians frequently use the marker in laboratory tests to differentiate bacterial from viral infections, something that healthcare practitioners will soon be able to do in offices, enabling them to prescribe appropriate treatments more quickly, Westlake said. Such a test may be particularly useful when it is used to diagnose pneumonia for which an infection can be viral or bacterial, he said.
ProciseDx is certainly not alone in pursuing better options to help physicians make such a determination. For example, Duke University spinout Predigen Diagnostics and Stanford University spinout Inflammatix are separately developing multiplex platforms that use host gene expression signatures as a basis for tests that differentiate viral from bacterial infections.
Westlake noted that in the US physicians frequently order chest X-rays to help doctors diagnose pneumonia and determine the extent and location of an infection. However, ProciseDx anticipates that in the future its point-of-care instrument and tests, partly because they will be more affordable and convenient than X-rays, will help the firm achieve future placements for that application.
Overall, the point-of-care instrument has a place in helping clinicians diagnose both acute and chronic conditions, Westlake noted.
During the diagnosis of acute conditions such as inflammatory bowel disease, which includes conditions such as Crohn's disease and ulcerative colitis, patients taking a point-of-care test can immediately receive an appropriate treatment and forego an extended and stressful wait for laboratory results. For a condition that is less serious and more manageable, such as irritable bowel syndrome, a physician can right away reassure the patient, Westlake said, adding that the ProciseDx CRP test will give physicians the capability to differentiate among both conditions.
Geert D'Haen, professor of gastroenterology at the Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, said in an interview that many gastroenterologists who treat inflammatory bowel disease with biologic drugs are seeking to ensure that their patients receive appropriate levels of drugs to achieve and maintain remission. "With ProciseDx, we will be able to measure levels of infliximab and adalimumab in five minutes from fingerstick blood."
Infliximab (Janssen's Remicade) is used to treat a number of autoimmune diseases, and adalimumab (AbbVie's Humira) is used to treat rheumatoid arthritis, Crohn's disease, and ulcerative colitis, among other conditions. "Because we'll get that accurate information during the patient visit, we'll be able to incorporate it into our treatment decisions there and then," said D'Haen, a former chair of the International Organization for the Study of Inflammatory Bowel Disease who is an advisor to ProciseDx.
D'Haen noted that obtaining results of biologic serum concentration tests currently takes up to four weeks. When the ProciseDx test is available, patients will see health benefits from up-to-date information and efficiency benefits from fewer follow-up appointments, he added.
The market for IBD testing has heated up, with a number of companies and academic groups developing and/or marketing new tests.
Just last month, Schönenbuch, Switzerland-based Bühlmann Laboratories announced that its Calex Cap fecal extraction device has received 510(k) clearance for use with its fecal calprotectin test. The firm said that its test can help clinicians diagnose Crohn's disease and ulcerative colitis, and differentiate between inflammatory bowel disease and inflammatory bowel syndrome.
Cambridge, UK-based PredictImmune recently announced an expansion of a worldwide licensing agreement to allow the UK firm first right of refusal to new technologies from Cambridge Enterprise. A prior deal between the partners covered technology related to the prediction of disease outcome in relapsing-remitting autoimmune and inflammatory disease, specifically for IBD, including Crohn's disease and ulcerative colitis.
Meanwhile, San Diego-based Progenity recently announced it has acquired Medimetrics' patent portfolio for ingestible device technologies and that it is developing devices that can help diagnose and treat GI diseases, such as IBD. And researchers at the Medical University of Warsaw in Poland have developed a biomarker that they said could be the basis for a noninvasive test to assess intestinal diseases such as IBD.
ProciseDx has been working in stealth mode with Nestlé's support for three years to develop the diagnostic platform. The company developed the instrument to provide results within a few minutes, and so that it could be flexible enough to enable the addition of new tests by adding antibodies specific to various medical conditions, Westlake said.
The firm developed its instrument in house at Prometheus Laboratories, leveraging the firm's core capabilities for laboratory gastroenterology testing.
"We saw the opportunity to bring some tests out of the laboratory and into the doctor's office, recognizing that we could enable faster testing with the quality available from laboratory instruments," Westlake said.
Prometheus markets a number of laboratory tests that are aligned with conditions for which ProciseDx intends to offer tests at the point of care.
According to Prometheus' website, its 7C4 laboratory diagnostic test measures 7α-hydroxy-4-cholesten-3-one levels to help determine if bile acid malabsorption may be the underlying cause of patients' gastrointestinal-related symptoms. Its Crohn's Prognostic test combines serologic markers, including anti-CRir1, anti-OMPC, and DNAse sensitive pANCA, as well as genetic markers, including NOD2 variants SNPs 8, 12, and 13, to quantify a patient's probability of developing disease complications over time. Further, its Celiac Plus test combines serologic, genetic, and inﬂammation markers to help identify active celiac disease and stratify relative risk.
"The technology we use is sufficiently flexible that we are not limited to gastrointestinal testing," said Westlake. "We can go into lots of other doctors' offices with a menu of different tests, and the technology can handle a lot of different immunoassays," he said.
The firm is not yet providing details of the types of biomarkers it is using for future tests but expects to announce relevant information in parallel with FDA submissions for the assays, Westlake said.
Developing the instrument under the wing of Prometheus has given the developers "a lot of domain expertise" and contacts with diagnostic industry thought leaders. "As a result, when we were going through the development process and testing whether the instrument was robust enough, we had access to the right people to do that," he said.