Molecular diagnostic company DioGenix has released clinical validation data for its next-generation sequencing-based multiple sclerosis test, MS Precise.
The Gaithersburg, Md.-based company launched a blinded, multi-site prospective trial of its test in the beginning of 2013, evaluating patients without a diagnosis but who had some level of clinical presentation — either suspected myelination or multiple sclerosis-like presentations in their MRIs or cerebrospinal fluid, DioGenix CEO Larry Tiffany told Clinical Sequencing News.
In a trial involving 13 centers and 20 physicians, DioGenix enrolled 200 individuals that were undergoing a comprehensive evaluation using current standard-of-care imaging of the central nervous system and oligoclonal banding analysis of cerebral spinal fluid and blood. The trial then compared MS Precise testing to these results, yielding a sensitivity of 78 percent and a specificity of 82 percent for the NGS test.
Oligoclonal banding is the primary cerebral spinal fluid analysis test, but has a high false positive rate, with sensitivity and specificity hovering around 78 percent and 37 percent, respectively.
Following the clinical validation, Tiffany said the company's next step is to proceed with commercialization, which will involve expanding its laboratory, becoming CLIA certified, and raising additional funds to support commercialization. Late last year, DioGenix secured $3.2 million in private financing to support the clinical trial.
The MS Precise test is based on research by Nancy Monson at the University of Texas Southwestern. DioGenix has an exclusive license to the intellectual property.
The test isolates and sequences the entire approximately 300-bp hypervariable region of patients' B-cell genomes and assesses mutational frequencies across six hotspot codons. Based on the mutational frequency, a score is assigned, with 6.8 as the cutoff for MS.
DioGenix initially worked with Roche's 454 GS system because at the time it was the only system with long-enough read lengths to sequence the entire 300-bp target. However, Tiffany said the company is now also evaluating Illumina's MiSeq and Life Technologies' Ion Torrent PGM.
In addition, the test currently relies on isolating cells from the cerebral spinal fluid, but Tiffany said that the company is also conducting a clinical study to see whether the test is as effective on blood samples.
Moving forward, Tiffany said that DioGenix plans to follow the patients enrolled in its clinical validation study to see which are progressing more rapidly, which are responding to therapy, and which develop resistance to therapy. It will then look for additional biomarkers within the hypervariable region of the B-cell genome that correlate with clinical outcome. Eventually, Tiffany said that this would open the door to develop additional tests associated with outcome or that correspond with other neurological diseases, although he declined to provide specifics.
Competition-wise, he said that there are very few companies developing MS tests, and that the oligoclonal band test was developed in the 1950s and has not changed at all. MS Precise will provide greater resolution, Tiffany said, and ultimately earlier and better diagnoses.
Over the last five to eight years, new therapeutic options have been made available, Tiffany said, but innovation on the diagnostic side has lagged.
Clinicians now have "good tools to treat patients, but they are expensive and [can] create a risk to the patient," he said. "The risk and expense is worthwhile if the patient actually has MS, but if not, it's creating a large expense to the patient or third party payor and subjecting that patient to unnecessary risk."
Tiffany said that a price for MS Precise has not yet been determined, but will be similar to other molecular tests. While it will be more expensive than oligoclonal banding, he thinks that providing a more accurate test will save patients and payors money in the long run by avoiding unnecessary therapy or providing an earlier diagnosis that will enable treatment to be started sooner.