NEW YORK (GenomeWeb) – Some developers of noninvasive prenatal tests in Europe are taking a different strategy than those in the US, choosing to focus on launching CE-marked in vitro diagnostic tests that clinical laboratories can purchase as a kit, as opposed to offering laboratory-developed tests as a service.
Recently, Belgium-based molecular diagnostic company Multiplicom launched an early-access program for its CE-IVD, dubbed Clarigo, and is planning a broader commercial launch of the test in Europe this fall. Earlier this month, UK-based Premaitha Health received the CE mark for Iona, its IVD for fetal aneuploidy in chromosomes 21, 18, and 13.
The companies are going this route as opposed to the LDT model followed by US providers because the prenatal testing market in Europe and the UK is a distributed one. In addition, Europe's regulatory hurdles for developing a CE-IVD are significantly fewer than those for a pre-market approval in the US.
"The regulatory burden for a PMA is an extremely high one," Premaitha CCO Peter Collins told GenomeWeb at last week's Molecular Medicine Tri-Conference in San Francisco. As such, he said the company has no current plans to launch its test in the US.
Meantime, Multiplicom CEO Dirk Pollet told GenomeWeb in a phone interview that the company has not yet decided if it will bring its test through FDA clearance in order to launch it in the US, but said that if it did, it would do so in conjunction with a partner.
Multiplicom's Clarigo test is a targeted sequencing-based test that screens for trisomies 21, 18, and 13, as well as X-chromosome aneuploidy. Pollet said that the company has validated the test on both the Illumina MiSeq and also Thermo Fisher Scientific's Ion Torrent PGM.
The company recently began enrolling clinical labs into its early-access user program and anticipates a broader commercial launch in October, Pollet said.
He added that the test is based on Multiplicom's core targeted sequencing technology — multiplex amplification specific targets for resequencing (MASTR). The company's MASTR assays use a two-step PCR protocol to first amplify a targeted region of interest and then to incorporate molecular barcodes. Multiplicom also sells CE-IVD molecular ID kits specific to the MiSeq and PGM that are designed to be used in combination with its MASTR assays.
The Clarigo test is Multiplicom's first NGS entry into reproductive health, but it also sells NGS CE-IVD tests for hereditary BRCA mutations, cystic fibrosis, Mediterranean Fever, and a number of research-use-only kits for hereditary diseases and somatic mutation testing.
Although Pollet said the company has not settled on an exact price for the Clarigo test, he said that it is aiming for the €250 ($282) per sample range, which would put it at roughly half the price of other noninvasive prenatal tests in Europe. The "reduced workload due to the reduced sequencing capacity and analysis of our approach" is what will enable the lower price, Pollet said. However, he noted that the eventual cost to the patient will depend on the clinical lab or hospital offering the test.
The ability to offer the test at a lower price was a key reason why Multiplicom chose the targeted sequencing route as opposed to the whole-genome shotgun sequencing approach used by NIPT providers such as Sequenom and Illumina.
"Provided that the price of the test is low enough, we think that [NIPT] will become an integral part of the workup of all pregnancies," Pollet said.
In addition, Pollet said, sample prep and analysis are simpler "because you are always looking at and counting the same amplicons."
Premaitha, meantime, has developed its CE-IVD to run on Thermo Fisher's Ion Proton, and like Sequenom and Illumina, it uses a whole-genome sequencing approach.
However, unlike those companies, Premaitha is taking a more conservative approach to the types of chromosomal abnormalities it analyzes. Currently, Premaitha looks at only trisomies 21, 18, and 13, although Collins said that a second version will also evaluate sex chromosome aneuploidies. But, "the jury's still out on microdeletions," he said, adding that there needs to be more research on the impact of such abnormalities, given that there can be a significant amount of phenotypic variation, and how to counsel women with affected fetuses before the company incorporates those into its test.
Collins said that one reason it is selling Iona as a kit, as opposed to running it as a service, is that "Europe doesn't have the central lab approach that exists in the US," where hospitals and clinicians all over the country send tests to Quest or Laboratory Corporation of America. Instead, there are many hundreds of laboratories that offer maternal serum screening to Ob-Gyns, he said.
Selling a CE-IVD will "enable labs that currently offer [maternal serum] testing to offer the NGS test," Collins said. The Iona test will require that labs either purchase or already have access to the Proton, as well as Qiagen's QIAsymphony and PerkinElmer's SciClone, since those are the systems on which Premaitha validated the test. The Iona kit includes all the reagents necessary to run the test. If a lab wanted to run the Iona test on a different sequencing platform, it would no longer be considered a CE-IVD, Collins said.
Neither Premaitha nor Multiplicom licensed technology from Sequenom, Illumina, Ariosa, or any other NIPT provider. Both Collins and Pollet said that after analyzing the field, neither had concerns.
"The current patents that exist are methods patents," Collins said, "and our method is sufficiently different."
Pollet added that Multiplicom did a "fairly extensive operating analysis in Europe and the US," and "because the approach uses our own core technologies," the company felt that it did not need to license other providers' technology.