Biotech startup EpicGenetics last month launched its FM/A protein biomarker test for fibromyalgia with the aim of providing an objective method of diagnosing what has traditionally been a difficult to pin down disease.
Based on research published in December in the journal BMC Clinical Pathology, the test has drawn criticism from several rheumatologists and fibromyalgia researchers who have questioned whether the underlying data supporting it is sufficient.
Nonetheless, Epic booked close to 1,000 sales of the test in its first month on the market, Bruce Gillis, the company's founder and CEO, told ProteoMonitor this week. The Santa Monica, Calif.-based company offers the test out of its CLIA lab at a price of $744. Patients can either order it through their physician or directly from Epic, in which case they are required to fill out a questionnaire that Gillis said the company reviews to determine their eligibility for the test.
The test diagnoses fibromyalgia by measuring levels of five cytokines and chemokines produced by white blood cells upon challenge with mitogens. According to findings by Gillis and his colleagues at the University of Illinois College of Medicine, where he holds an unpaid faculty appointment, fibromyalgia patients produce significantly lower levels of these five proteins than do healthy individuals.
The researchers first identified this relationship in a pilot study of 17 fibromyalgia patients and 17 healthy controls, Gillis said, after which they moved on to the study detailed in the BMC paper. That work applied the test to 110 fibromyalgia patients and 91 healthy controls, finding that it could identify fibromyalgia cases with a sensitivity of 93 percent and specificity of 89 percent.
Characterized by chronic widespread pain and sensitivity to pressure as well as symptoms including fatigue, bowel problems, and cognitive dysfunction, fibromyalgia was estimated by a recent Mayo Clinic study to affect as much as 6 percent of the population.
Fibromyalgia is recognized as diagnosable by the US National Institutes of Health and the American College of Rheumatology, but given that it typically presents as a collection of subjective conditions, diagnosis can prove challenging.
This, Gillis said, has led to many physicians treating the disorder like "it's not an authentic medical problem.
"Patients with fibromyalgia are often treated as if they are bogus, as if there is nothing wrong with them," he said.
The FM/A test, Gillis said, aims to remedy this situation by providing a set of objective criteria against which patients can be evaluated.
Some researchers in the field, however, have responded skeptically to Gillis' and Epic's claims, noting the relatively small sample size of the BMC study and the fact that the identification of a decrease in cytokine and chemokine activity in fibromyalgia patients runs counter to many previous findings.
"I don't personally think that [the FM/A] test has any diagnostic value given what we know at present," Daniel Clauw, director of the Chronic Pain and Fatigue Research Center at the University of Michigan and a fibromyalgia expert, told ProteoMonitor via email.
"These results are out of line with previous results of cytokine assays that either showed normal or increased (not decreased) levels of cytokines," he added, noting that given this inconsistency with previous studies, additional studies evaluating the Epic markers were required.
In particular, he suggested the researchers replicate the results in a different sample cohort and have another independent group replicate the results.
Clauw also noted that the BMC study looked only at fibromyalgia patients and healthy controls. Ideally, he said, the test would be evaluated against a cohort of controls with disorders that could be mistaken for fibromyalgia in order to demonstrate the marker panel's specificity for the disease.
Roland Staud, a rheumatologist and fibromyalgia expert at the University of Florida College of Medicine, also criticized the research behind the test, telling ProteoMonitor that the BMC paper "draws conclusions which are mostly speculative and unconvincing," adding that it would have benefited "from better controls."
Gillis said that with the test now on the market, the company plans to continue to collect data on its performance from customers and added that thus far the original sensitivity and specificity numbers appear to hold up in the larger sample size.
However, fibromyalgia researcher Daniel Wallace, a clinical professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles and a member of Epic's scientific advisory board, told ProteoMonitor via email that the FM/A test would be useful for less than one percent of fibromyalgia patients.
"I would only use the test to follow a [fibromyalgia] patient's response to [treatment] if it needed to be quantitated or as part of a clinical trial," he said.
He added that "rarely, a patient with bipolar illness, for example, can be misdiagnosed as [fibromyalgia], and the FM/A would be useful here. It can also be used to differentiate depression from [fibromyalgia] in that the cytokine pattern in these disorders is different, but almost all the time the distinction can be made clinically."
Epic, however, is offering the test as a diagnostic for fibromyalgia in the general population, a set of patients well outside the categories defined by Wallace.
One of the subsets of customers Gillis said the test could attract are fibromyalgia sufferers looking for an objective diagnosis for use in workers' compensation or disability cases. "We're hopeful that because we have some objective criteria, those people who have to decide disability will use the test," he said.
In this regard, Epic is similar to a previous venture of Gillis', the firm Cytokine Institute, which he founded to commercialize a genomics-based test that the company claimed was capable of detecting benzyne exposure using gene expression. Based on research published by Gillis in the journal Genomics in 2007, the test, called msds1, was intended for use in workers' compensation lawsuits as an objective measure of a person's benzyne exposure. According to a 2007 article by the BBC, it was used in at least 20 civil cases in California.
Like FM/A, the msds1 test drew criticism from outside researchers – most pointedly from University of California, Berkeley professor of toxicology Martyn Smith, who, in a 2008 commentary in the International Journal of Occupational and Environmental Health called the research underlying the test "junk science" and added that "no knowledgeable scientist would accept the msds1 test as useful information in attributing disease causation."
Responding to these remarks, Gillis, who was formerly the head of UCLA's Department of Occupational Medicine, suggested to ProteoMonitor that Smith was biased due to his role as a paid expert for litigants in benzyne exposure cases, a role that Smith disclosed in his commentary.
Gillis said that the Cytokine Institute was no longer active, though he did not provide further details, saying only that "we chose to exit the wonderful world of litigation. We are researchers and scientists, not paid witness prostitutes."
Wallace said that he was unaware of Gillis' previous ventures, adding that he had met him for the first time three months ago.
He added that "in his favor, Dr. Gillis has vast resources and has put together a blue chip [scientific advisory board] and plans to fund cutting-edge basic science research. That is the sole reason for my involvement [as a member of Epic's scientific advisory board], but if this does not pan out, my involvement is temporary."
Indeed, Epic has appointed 11 researchers to its scientific advisory board, including Ernest Brahn, professor of medicine, rheumatology at Ronald Reagan UCLA Medical Center; Simon Helfgott, associate professor at Harvard Medical School; and Josef Smolen, head of the Department of Rheumatology at the University of Vienna and current president of the European League Against Rheumatism.
Gillis said that he is the sole investor in Epic, funding commercialization of the FM/A test and the company's CLIA lab.
"We don't have any venture capitalists or angel investors or drug company money," he said. "It's all internally driven financially. Fortunately, I can afford to provide the money."