Quest Diagnostics this week launched a pair of protein biomarker tests for the diagnosis of rheumatoid arthritis.
The tests are based on the 14-3-3eta protein biomarker, which Quest licensed from Canadian biotech firm Augurex. One test consists solely of the 14-3-3eta protein while the other is a panel including both 14-3-3eta and the established RA protein markers anti-cyclic citrullinated peptide antibodies and rheumatoid factor.
Both tests are intended as aids in diagnosing RA, and early-stage RA in particular, Stanley Naides, Quest's medical director, Immunology R&D, told ProteoMonitor.
Naides noted that previous studies have suggested 14-3-3eta might also have other uses, including as a marker of RA disease activity and as a predictor of which RA patients might respond to treatment with TNF-alpha inhibitors. He said, however, that Quest plans to market the tests released this week solely for diagnosis of RA.
Prompt diagnosis of RA is a key part of managing the disease in that it allows for early treatment, which can reduce joint damage and improve long-term function and the likelihood of remission. Conventional markers like CCP antibodies and rheumatoid factor can miss the disease in its early stages, however.
The new panels therefore "address a significant gap in the continuum of care of RA," Wendy Bost, Quest's director of media relations, told ProteoMonitor, "namely, the ability of physicians to reliably detect early-stage RA," which affects approximately 1.3 million people in the US.
For Vancouver, British Columbia-based Augurex, the Quest tests represent its first products to market. Formed in 2007 with the aim of commercializing the 14-3-3eta marker, which it licensed from the University of British Columbia, Augurex has spent the last six years gathering clinical data on the protein and its potential use for diagnosis of RA, said CEO Norma Biln.
While Quest holds the US rights to the test, Augurex also plans to sell the test globally, she told ProteoMonitor. The company expects to receive an EU CE mark for the test within the next several weeks and Health Canada approval in the third quarter of this year. It has targeted Europe as the next market for launch of the diagnostic and is also pursuing deals with either lab services companies or test distributors in Asia and Australia, Biln said.
She added – as Quest's Naides noted – that 14-3-3eta might also prove useful for tracking disease activity in established patients and identifying responders to anti-TNF-alpha drugs. Augurex has performed studies investigating the protein's utility in these roles, Biln said, characterizing these efforts as "close behind" the company's work establishing the protein as a marker for early diagnosis.
She added that the company recently had abstracts accepted to the European League Against Rheumatism Annual European Congress of Rheumatology this June that will detail research that "will further illuminate the prognostic utility as well as the therapy monitoring [utility]" of the protein.
In addition to 14-3-3eta, Augurex is investigating autoantibodies to the protein and post-translationally modified forms of the protein that could also prove useful in arthritis diagnosis and management, Biln said.
With regard to the autoantibody work, she said the company had observed that measuring levels of these proteins along with 14-3-3eta significantly increased the marker's diagnostic ability. Augurex is currently in the process of preparing data from this research for publication, she said. The company is also investigating citrullination of 14-3-3eta as a biomarker for RA.
Quest's license agreement with Augurex – which the companies signed in October 2012 – concerns the 14-3-3eta marker only, Biln said. She declined to discuss any other aspects of the company's biomarker development program that might fall under the scope of their deal.
According to data provided by Quest, the 14-3-3eta marker alone is elevated in 60 percent to 82 percent of RA patients, compared to 32 percent to 82 percent for RF alone and 44 percent to 82 percent for CCP antibody alone. Combining all three markers, as in the second of the two RA tests that Quest launched this week, increases the sensitivity of the test to between 72 percent and 100 percent.
Noting the gain in sensitivity provided by the multiprotein panel, Naides said Quest was nonetheless offering the 14-3-3eta marker as a standalone test in order to provide doctors with a suitable array of options.
"A physician may not believe results of all three assays are required for a reliable diagnosis, or perhaps a patient received certain tests already, perhaps under care of a different doctor, and additional testing would be redundant and unnecessary," he said. "In these cases, single assays may be more appropriate."
Quest and Augurex are not the first to enter the market for RA protein biomarkers. Most notably, Crescendo Biosciences in 2010 launched Vectra DA, a 12-protein panel for measuring disease activity in RA patients. In 2011, Myriad Genetics made a $25 million debt investment in Crescendo that gave it a three-year option to purchase the company (GWDN 9/9/2011).
Vectra DA is aimed primarily at tracking disease activity in established RA patients as opposed to early diagnosis, and both Quest's Niades and Augurex's Biln said they don't view it as a competitor to the 14-3-3eta-based tests. However, the products' potential uses do overlap, particularly with regard to identifying responders to anti-TNF-alpha drugs.
A study published last year in the journal Arthritis Care & Research suggested that Vectra DA might prove useful in identifying responders to a given drug early in treatment, finding that the test identified significant changes in clinical responders to methotrexate and anti-TNF therapies as early as two weeks after the start of treatment (PM 7/6/2012).
Also, last year Crescendo presented posters at the EULAR Annual European Congress of Rheumatology indicating that Vectra DA tracks RA patient response to anti-TNF therapy and patient response to treatment with the Jak inhibitor tofacitinib.
The company presented data as well at the 2011 American College of Rheumatology and Association of Rheumatology Health Professionals' annual meeting demonstrating that the test could identify patients responding to anti-TNF-alpha drugs.
Opko Health is also exploring whether its synthetic peptide array platform can detect proteins predictive of patient response to rheumatoid arthritis therapy. The company is currently collaborating with Bristol-Myers Squibb on work investigating protein markers for predicting response to the rheumatoid arthritis drug abatacept, marketed by BMS as Orencia (PM 1/18/2013).
According to Biln, in addition to an RA biomarker, 14-3-3eta might also prove a drug target for the disease. Augurex has published data indicating that the protein "drives many inflammatory and joint damage factors" and has established a research program investigating its potential as a drug target.
"If that is successful, then we have a personalized medicine where you have a biomarker that tells you how much of [the target] is there, and then a drug that reduces expression," she said. "Then you can tailor therapy and monitor patient response. So there's a lot of work for us to do."
Biln said the company would likely seek to partner with a larger pharma firm to push these therapeutic efforts forward, but it had not yet established any such collaboration.