NEW YORK (GenomeWeb) – Premaitha Health has reported that its cell-free DNA-based screen for fetal aneuploidies performed with perfect sensitivity and specificity.
Trisomies 13, 18, and 21 have been increasing in incidence, according to the US Centers for Disease Control and Prevention. But, common screening approaches based on ultrasound findings and other markers have false-positive rates that lead many women to seek an invasive diagnostic procedure like an amniocentesis or chorionic villus sampling when it may not be necessary.
Noninvasive prenatal testing (NIPT) providers — which include Roche's Ariosa, BGI, Illumina, Natera, and Laboratory Corporation of America's Sequenom, in addition to Premaitha and others — say that screening with their tests might bring the numbers of invasive tests performed down by identifying women at the highest risk.
As they reported in Fetal Diagnosis and Therapy this month, Premaitha researchers built an automated next-generation sequencing-based workflow and relied on a cohort of almost 250 high-risk women to develop an algorithm to determine the likelihood of trisomies from circulating fetal DNA. When they gauged their algorithm's sensitivity and specificity on a separate cohort, the researchers reported that their CE-marked in vitro diagnostic test, called Iona, had 100 percent specificity and sensitivity.
"We set out to build a test that could be used by [local labs] and that technicians in two weeks could learn to do genetic testing," William Denman, Premaitha’s chief medical officer said in an interview. "That's why writing this paper was important — to show that we've accomplished that."
Premaitha launched its Iona test in February 2015. Cell-free DNA is extracted from the blood samples and fetal DNA is isolated for sequencing on Life Technology's Ion Proton platform. The results are then fed into Iona's bioinformatics pipeline.
Denman added that the test could be run in a local biochemistry lab without the need for highly trained genetics technicians, and that from extraction to analysis, the test takes three days.
As described in the paper, to develop that screening algorithm, the Premaitha team used a set of 239 samples from women at high risk of trisomies. After excluding four samples — three lacked corresponding invasive diagnostic test results and one was from a woman found to have cancer — this algorithm development set included 36 trisomy 21, 26 trisomy 18, and four trisomy 13 samples.
They tested the model they developed on a separate set of 111 samples, though one sample failed the fetal fraction validity check. They reported that all the Iona-based results matched those provided by amniocentesis or chorionic villus sampling, giving 100 percent sensitivity and specificity.
Since their small validation study, thousands of samples have been run on the Iona test, Denman said. While their sensitivity and specificity have remained good, they have had a handful of false positives, he said, attributing them to biological features like confined placental mosaicism.
According to Denman, the Iona test is largely comparable to others on the market. He noted that Premaitha presented data at a recent meeting indicating that the Iona test performs similarly to BGI's NIFTY test. In the version of the poster at the company's website, researchers reported that for a set of 514 paired samples, the Iona test identified 15 instances of trisomy 21, as did the NIFTY test. They differed, however, on the number of samples with trisomy 18, with Iona finding three and NIFTY four. That discordant sample was determined to be a false positive by the NIFTY test, they said. They also said that NIFTY required 10 redraws from the mother to Iona's two.
"We are the equivalent to anybody else on the market," Denman said.
The Iona test being offered now has the "same bones" as the one described in the paper, he said. He added that the firm has made tweaks to the software to improve the workflow, increase efficiency, and decrease costs, but that those changes work with the equipment customers already bought.
As noted in the paper, the Iona test can also incorporate other patient data, such as maternal age or results from the first-trimester combined test that includes a blood test and ultrasound. Work to allow this customization is underway, according to the company.
Between its launch in February 2015 and March 2016, Premaitha reported it sold more than 17,000 tests to customers in the UK and Europe. In addition, the company has inked distribution deals to bring its test to Chile, India, Russia, Thailand, and the Middle East. Iona is also being used in labs in France and Greece.
The company has also acquired Yourgene Bioscience, a Taiwanese noninvasive prenatal screening provider, and in addition to installing its test in local labs, Premaitha has a service lab in the UK.
The firm is also facing a lawsuit. Illumina and its Verinata Health subsidiary filed a suit against Premaitha in 2015 over NIPT-related intellectual property. The suit claims that the Iona test infringes European patents relating to the use of cell-free fetal DNA for NIPT that Illumina licensed from Sequenom and Stanford University. Denman said that the company does not think it infringes the patents.