NeuroMark this week clarified that its Mark-C genetic test for suicidal ideation in patients treated with citalopram will be launched for investigational use only, pending positive results from two confirmatory trials. The firm will initially debut the test as a homebrew assay, which will likely make it the first genetic test for suicidal ideation.
The company said it plans to submit the test for FDA approval in 2008, but has not yet determined whether to submit under a 510(k) or for premarket approval.
“We assure you that we are working diligently to make the test one in which the physician will have confidence and one that encourages patients who are experiencing depression to seek treatment,” NeuroMark CEO Kim Bechthold told Pharmacogenomics Reporter this week.
Last month, NeuroMark announced that it will make available the Mark-C test on what it said was the strength of a National Institute of Mental Health study that linked the GRIK2 and GRIA3 genes to the risk of suicidal thoughts when patients are treated with the antidepressant citalopram [see PGx Reporter 10-31-2007].
That study, which involved approximately 1,800 of the 4,000 patients in the Sequenced Treatment Alternatives to Relieve Depression Study, known as STAR*D, sought to learn whether patients carrying mutations in the GRIK2 and GRIA3 genes are at risk of having suicidal thoughts when treated with citalopram, marketed as Celexa by Forest Labs. The study was published in the October issue of the American Journal of Psychiatry.
However, Francis McMahon, one of the study authors and director of the Genetic Basis of Mood and Anxiety Disorders program at NIMH, told Pharmacogenomics Reporter that without having replicated the study results, the findings may be overestimated, and it may be premature to launch a genetic test.
Although NeuroMark issued a press release in early October announcing the “immediate availability” of the Mark-C test, the company this week explained that it does not intend to broadly launch the test until two confirmatory studies are completed and yield positive results. One study will be conducted by an independent research institution and the other will be sponsored by the company.
NeuroMark’s prospectively designed study will be “open to selected physicians and patients who wish to participate using the Mark-C test on an investigational use-only basis,” Bechthold said.
“Other than within the NeuroMark confirmatory study, the test is not commercially available at this time,” Bechthold noted. “After analyzing the data from the confirmatory studies we will announce when the test will become available.”
NeuroMark’s Mark-C employs PCR technology followed by primer extension. Samples are then analyzed by an Applied Biosystems capillary electrophoresis sequencer. In the NIMH study, researchers genotyped patients using Illumina’s GoldenGate assay, and in confirmatory studies they are using Illumina’s Infinium 109K chip.
“Other than within the NeuroMark confirmatory study, the test is not commercially available at this time. After analyzing the data from the confirmatory studies, we will announce when the test will become available.”
The test will cost approximately $390 and will be performed at Orchid CellMark’s CLIA-approved laboratory in Dayton, Ohio.
“Insurers have not been contacted as yet regarding reimbursement of the test,” Bechthold said. “We have completed an analysis of CPT codes to be suggested to physicians to aid them in obtaining reimbursement for their patients, and we have established a reimbursement hotline to further assist physicians when the test is made available commercially.”
NeuroMark said that its test can interrogate four different single markers occurring in four separate genes that may be linked to suicidal ideation in patients treated with Celexa. According to the company, the STRA*D trial identified all four genes that the Mark-C assay tests for. However, the NIMH in the American Journal of Psychiatry article only discussed two genes, GRIK2 and GRIA3.
“Luckily the sensitivity and specificity of the four markers together is remarkable,” Bechthold said. “The test results currently can also predict for the physician, in chart form, his patient’s risk, from 1 percent to 59 percent. This gives the physician an understanding of new genetic information for treating his patient in just a few seconds.”
The results from NeuroMark’s confirmatory trial will be published in an outcomes database. This data will also be published in journals and posted on the company’s website.
The NIMH is currently conducting a confirmatory trial to validate its initial finding in a study involving approximately 2,000 STAR*D patients. Although NeuroMark is not affiliated with the NIMH effort, the company said that its own confirmatory trial is of similar size.
According to NeuroMark, although it is a “significant challenge” to confirm data from a study as large as STAR*D, initial results from its own confirmatory trial look promising to investigators.
“We believe it will be good if public confidence is restored in medications that can be life saving when treatment for depression would be beneficial for the patient,” Bechthold said. “The new fields of pharmacogenomics and preventative medicine envision exactly this type of application.”
Following FDA’s requirement that a “black box” be added to the labels of all antidepressants, prescriptions for these types of drugs began to drop off. NeuroMark cited a study by Gibbons et al. in the September issue of the American Journal of Psychiatry that linked the decrease in antidepressants scripts to a significant rise in US suicide rates between 2002 and 2004.