Correlagen Diagnostics last month launched a genetic test that detects hypertrophic cardiomyopathy, an inherited disease that is the leading cause of sudden cardiac death among children and young adults.
The HCM test, based on bidirectional sequence analysis, is available as a homebrew test. According to Correlagen, the US Food and Drug Administration has determined that a nod from the agency is not necessary to market the test.
“HCM is caused by a defect in one of several genes and can lead to severe problems including heart failure, stroke, or sudden death,” Correlagen said. “There is no cure for HCM, but early diagnosis allows for timely initiation of lifestyle changes and medical interventions,” including beta blockers, calcium channel blockers, and implantable cardioverter-defibrillators.
HCM is the most common inherited cardiovascular disease affecting one in 500 people. A child of a parent with HCM has a 50 percent chance of getting the disease, and the disease accounts for 40 percent of all cardiac deaths on athletic playing fields.
Correlagen’s test, which requires a cheek swab or a small blood sample, can confirm that a patient with otherwise inconclusive symptoms has the illness, the company said.
HCM is caused by mutations in any of the 12 genes that encode the contractile apparatus in cardiac myocytes. More than 200 individual mutations have been linked to the disease, and Correlagen’s product tests for eight of these genes, which are associated with about 70 percent of all familial cases of HCM, Correlagen CEO David Margulies told Pharmacogenomics Reporter in an e-mail.
The Correlagen assay tests for mutations in MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC. It takes approximately two weeks to receive results from single-gene tests and between three to four weeks for multi-gene test panels, Correlagen said. The technical accuracy of the test is >99.9 percent.
“Interpretation of sequence variation is less precise and is as good as the association studies that correlate the specific variant with disease or the algorithms which predict the impact on protein function from a disease variant,” Margulies said.
“In a family with the phenotype, which is the important measure, and given that this is not a very common phenotype, predictive accuracy is extremely high,” he added. “Predictive accuracy would be lower if the test were used to screen the general population, though predictive accuracy will grow over time as more sequence variants are seen and evaluated.”
The Harvard Partners Center for Genetics and Genomics currently markets a competing diagnostic that tests for mutations in two panels. Panel A (HCM-A) includes five of the most common genes for HCM: MYH7, MYBPC3, TNNT2, TNNI3, and TPM1, yielding a 50- to 60-percent detection rate of a pathogenic mutation among patients with clinically evident disease. Panel B (HCM-B) includes genes ACTC, MYL2, and MYL3, and yields a detection rate of a pathogenic mutation of between 5 percent and 10 percent.
The combined detection rate for the HPCGG test, if a patient is tested for mutations on both gene panels, ranges between 55 percent and 70 percent. According to HPCGG, its assay has greater than 99.9 percent accuracy to detect mutations in the sequence analyzed.
According to information posted on HPCGG’s website, the cost of mutation screening of five genes is $3,000, and an additional $1,150 for mutation screening for the three other genes. HPCGG offers a reduced testing price of $250 to screen for mutations of family members of patients who have mutations correlated to HCM.
“Fortunately, many physicians already understand the importance of diagnosing HCM. They are familiar with the limitations of using imaging studies and electrophysiological studies to diagnose the disease, and they've been eagerly awaiting genetic testing.”
Correlagen noted that its testing service is differentiated from HPCGG’s product by “shorter turn-around times, more comprehensive result reports, and a much more patient-friendly payment policy.”
However, Correlagen’s testing services are more expensive than the HPCGG tests. Mutation testing for patients on the full panel of eight genes on Correlagen’s product costs $4,745; on the major panel including TNNT2, MYH7, and MYBPC3 genes is $3,600; on the minor panel including TNNI3, TPM1, MYL2, MYL3, and ACTC genes is $1,980.
Patients can lower their out-of-pocket costs by signing up for the company’s “Capped Patient-Payment Plan.” Insured patients who sign up for CPPP are responsible for only 15 percent of the total test cost, regardless of the amount insurance companies reimburse for the test. Under the CPPP, patients pay $711.75 for testing on the full panel, $540 for testing on the major panel, and $297 for testing on the minor panel.
Costs are even lower for testing for family members of HCM patients. “Once the familial mutation has been identified, family testing is very inexpensive,” Margulies said.
“Correlagen is working closely with insurance companies and organizations such as the [Hypertrophic Cardiomyopathy Association] to seek full coverage of the test cost,” said Margulies. “Currently, reimbursement levels from commercial insurers depend on variables such as carrier and quality of plan.”
According to Margulies, Correlagen will work directly with HCM centers around the country to help doctors understand how to use genetic testing information in their practice, and how to counsel family members.
“Fortunately, many physicians already understand the importance of diagnosing HCM,” Margulies said. “They are familiar with the limitations of using imaging studies and electrophysiological studies to diagnose the disease, and they've been eagerly awaiting genetic testing.”