NEW YORK (GenomeWeb) – Biotech firm Evogen presented new data from its epilepsy diagnostic development program last weekend at the American Epilepsy Society annual meeting in Washington D.C., that showed its test may be able to differentiate people with epilepsy from those without.
The data came from a recent study of 31 epilepsy patients and 29 healthy controls with no history of seizures in which the company identified a panel of seven blood-based proteins that could distinguish between the two groups with sensitivity of 100 percent, specificity of 90 percent, positive predictive value of 91 percent, and negative predictive value of 100 percent.
Evogen is now preparing to test the markers in larger cohorts with the ultimate goal of launching it as a laboratory-developed test through its CLIA facility.
Evogen intends the test to rule out epilepsy in patients who present with seizures of unknown cause. According to the company, only around 20 percent of seizures are due to epilepsy, but it can be challenging and time-consuming to distinguish between epileptic and non-epileptic seizures, and during the diagnosis process patients can be inconvenienced by things like driving restrictions.
"There are a million patients a year who go to the emergency department, or a primary care physician, or a primary neurologist, and say, 'I had a seizure,'" said Richard St. Clair, the company's vice president, commercialization. In 80 percent of those cases, he noted, the patients either did not have an actual seizure at all, or the seizure was not due to epilepsy.
"Where we see there's a benefit is if we can really weed those patients out of the system, meaning out of the neurology platform, get them on to a better course of treatment for them, or a better course of diagnostics," he said, "and keep the [other] 20 percent and let them actually go through the neurology protocol to say, yes, you have epilepsy, and here's what we are going to do for you."
Typically, when a patient goes to the doctor for a seizure, they are evaluated with an electroencephalogram. However, said John Gledhill, Evogen's director of R&D and lab operations, EEGs are usually only effective if the patient has an electrical event while they are being evaluated.
"That is the gap we think we can fill," he said.
In the recent study, the Evogen researchers looked at a total of 51 plasma markers involved in inflammation, which is thought to play an important role in epilepsy. They arrived at a set of seven for their test — IL-16, TARC, TNF-a, MIP-1B, TRAIL, MMP-3 and P-cadherin.
This expands on a set of three markers the company initially planned to take to market as an epilepsy test. Those markers were originally identified by Peter Crino — formerly a researcher at the University of Pennsylvania and currently chair of neurology at the University of Maryland School of Medicine — and John Pollard, assistant director of the Penn Epilepsy Center. The two formed a company, Cognizance Biomarkers, to commercialize the markers, which Evogen acquired in 2016.
In a study presented at the 2016 AES meeting, the company measured the markers in 28 patients with epilepsy who had experienced an event within 24 hours and plasma samples from 29 healthy controls. They found that the test could distinguish between the two populations with sensitivity ranging from 89.3 percent to 93.9 percent and specificity between 75.9 percent and 83.3 percent.
Last year Evogen President and CEO Todd Wallach said the company hoped to launch that three-marker test, which it called EvoScore START, in 2017. However, Gledhill said, response from potential customers convinced the company to evaluate additional markers with the goal of improving the diagnostic performance.
The company has filed patents on all 51 proteins they looked at in the most recent study, St. Clair said. Gledhill added that while the seven-protein panel may not reflect the exact composition of the final test, the company "has a pretty good idea of which [markers] we like and which we are going to use in a validation study."
Gledhill said the company believes it has "a pretty quick path to market" for the test and added that he thought it would take a validation study looking at 100 or fewer samples to prepare the test for launch.
"Diagnostics are much different than pharmaceuticals where you need thousands of patients," St. Clair said. "For diagnostics, it's driven by statistics, and [you need] high double digits, maybe low hundreds" to validate.
Such an assessment runs counter to the example of most diagnostic development efforts, where hundreds to thousands of patients tested across multiple centers in multiple trials is the norm. Beyond the question of statistics, driving adoption among clinicians typically takes multiple validation studies along with clinical utility and health economic studies. Evogen has thus far presented data from two studies looking at a total of 117 patients with control cohorts made up of healthy individuals with no history of seizures rather than the intended patient population of individuals presenting with what they believe to be seizure-like symptoms that might be mistaken for epilepsy.
In addition to developing the test for evaluating patients, the company is also exploring its utility in helping pharma firms select clinical trial cohorts.
"We're working with pharmaceutical manufacturers now on their clinical trial enrollment to better understand who does and who doesn't have epilepsy," St. Clair said.
The company is also looking into other areas including traumatic brain injury and pain management where it believes inflammatory markers could be useful as diagnostics or for monitoring purposes.
Prior to acquiring Cognizance, Evogen's business centered primarily around biothreat detection, for which it offers its SpinCon platform for capturing airborne bioaerosols, vapors, and particulates, including pathogens, as well as its HyBeacon reagents, which are PCR probes for pathogen detection.
The company is profitable based on those businesses, and is using those profits to fund is diagnostics development program organically, said Gledhill.