NEW YORK – Bioinformatics company Allelica predicts that incorporating evidence from its polygenic risk score for coronary artery disease (CAD-PRS) into standard CAD risk assessments will improve the ability to identify higher-risk individuals while providing a cost-saving benefit to US healthcare systems.
The company is now talking with the US Food and Drug Administration regarding the possibility of regulatory approval for the CAD-PRS, currently marketed as a lab-developed test in collaboration with Clinical Enterprise, a CLIA-CAP lab in Massachusetts.
"We are working closely with FDA to understand the best way to [fully] commercialize this product," said Giordano Bottà, Allelica's CEO and cofounder.
Allelica's software allows healthcare systems and genetics laboratories to perform polygenic risk score analysis independently. It is optimized for genome-wide microarray and whole genome sequencing with low coverage on both Illumina and Thermo Fisher Scientific instruments.
Allelica and Illumina also have a licensing arrangement that allows Illumina to offer Allelica's PRS software to its customers via its Illumina Connected Analytics bioinformatics software platform. The companies are also codeveloping an Illumina Infinium genotyping array that includes curated content specific for PRS predictions.
In a study published last month in the Journal of the American Heart Association, researchers from Allelica, Illumina, and the University of Sydney suggest that using PRS as a metric in the pooled cohort equation (PCE) — a sex- and race-specific tool for estimating 10-year absolute rates of atherosclerotic cardiovascular disease events — to guide preventive statin therapy for coronary artery disease is cost-saving among US adults, from a payor perspective.
The four risk categories for CAD are labeled low, borderline, intermediate, and high. Statins can effectively prevent CAD among individuals within the high-risk category, but discriminating borderline and intermediate individuals, for whom different statin treatments — high-intensity and moderate-intensity statins — would be effective remains challenging.
"We focused on individuals at intermediate and borderline risk of coronary artery disease because their clinical management is uncertain," Bottà said.
Drawing from published patient data and factoring in costs for screening, doctor visits, and statin therapy, Allelica's model predicted that adding PRS to the PCE would avert at least 29 CAD and ischemic stroke events per 10,000 individuals over a five-year window. This translated to an average cost saving of $40 per person, amounting to approximately $1.6 billion in healthcare system savings overall.
The additional patients determined to have higher risk for CAD and ischemic stroke by the addition of PRS as a risk-determining factor within this cohort suggested that standard screening procedures miss approximately 4 percent of people who should be using statins.
The company hopes that these results will drive uptake of its CAD-PRS by convincing practitioners of its utility and payors of its cost effectiveness. Eventually, it hopes to see PRS more formally included in screening guidelines.
On Monday, the American Heart Association issued a statement affirming that the addition of PRS into the standard risk calculation for adult patients aged 40 through 75 "significantly improves prediction of cardiovascular events."
PRS are increasingly applied to other disease areas as well, either commercially, as in the case of Myriad's myRisk tool for estimating one's risk of developing breast cancer, or for research purposes, as in the case of schizophrenia, wherein its clinical utility remains unproven.
Along with other researchers, Allelica sees CAD as an area ripe for PRS application.
"The current paradigm of treatment for the disease lends itself to incorporating PRS into risk models related to CAD somewhat easier than for other diseases," said Derek Klarin, a vascular surgeon at Stanford University who has authored research papers on the clinical utility of PRS in CAD and was not involved in Allelica's study.
Genetic risk, he said "is known early in life, before the emergence of additional clinical risk factors."
Allelica did not measure the effects of environmental factors such as diet and exercise into its study, citing the challenges of making these measurements in real-world settings. Bottà commented that these factors are unlikely to have significantly affected the study's findings.
Klarin largely agreed with that assessment, saying that while adding other risk factors would aid in risk discrimination, "there is still some evidence that PRS does add orthogonal or additional pieces of information beyond what can be captured purely from clinical risk factors and current risk scores."
Allelica's next steps are to work with the FDA and key opinion leaders such as clinical directors to further expand into US healthcare systems and prepare its regulatory submission.
In support of eventual approval, the company is expanding its US sales team, seeking to hire 15 to 20 people over the next six months.
For now, the company is purely focused on the US market, with respect to its CAD-PRS, although Bottà noted that there is "a lot of interest" in the UK. The company is conducting a study on the application of PRS to prostate cancer risk in the UK and plans to announce results in the near future.
Last year, the company published a research letter in Circulation, showing that polygenic risk could modify CAD risk from low-density lipoproteins in a European cohort.
"We [are starting to] see many sharper clinical application of PRS," he said, "[where] the intended population is better defined and has better health outcomes and better cost savings associated with that."