NEW YORK (GenomeWeb) – Two years after acquiring Swedish startup Vanadis Diagnostics, PerkinElmer is preparing to launch the company's noninvasive prenatal testing technology as a low-cost and user-friendly alternative to existing NIPTs for fetal aneuploidy screening, with the goal of expanding access to cell-free DNA prenatal screening.
Despite the rapid expansion of DNA-based noninvasive prenatal screening in recent years, driven by companies such as LabCorp's Sequenom, Natera, Illumina, and Roche's Ariosa, the majority of pregnant women in many countries are currently not getting NIPT, mainly because of high cost and lack of insurance coverage. "Driving solutions that make it cost effective for screening programs to implement NIPT is what we want to do," said Olle Ericsson, Vanadis' general manager.
Earlier this month, the company published a proof-of-concept study of the Vanadis technology for trisomy 21 detection in Scientific Reports, a collaboration with Kypros Nicolaides at the Harris Birthright Research Centre for Fetal Medicine in London and others.
For that study, they analyzed 286 clinical samples and correctly identified all 30 pregnancies affected by trisomy 21. They were also able to analyze samples with a fetal fraction of cell-free DNA as low as 2 percent.
The Vanadis team has since developed the test to also allow the detection of trisomy 13 and 18 and plans to show performance data for those later this year, Ericsson said.
The assay consists of a number of probe hybridization and enzymatic steps, followed by imaging, and does not involve next-generation sequencing, microarrays, PCR, or complex bioinformatics.
First, cell-free DNA is isolated from a maternal blood sample and fragmented using a restriction enzyme. Next, a set of probes complementary to the three target chromosomes 13, 18, and 21 – about 3,500 for each – and backbone oligonucleotides with a chromosome-specific tag, are added. The probes facilitate the ligation of the target DNA to the backbone oligo, resulting in single-stranded DNA circles.
After this, rolling circle amplification by a polymerase creates sub-micrometer-sized DNA bundles from each circle. These DNA bundles are then labeled with fluorophores according to their chromosomal tag — a different label for each chromosome — and added to a 96-well plate, and then immobilized on a nanofilter membrane on the bottom of the plate.
Finally, the labeled DNA blobs are imaged through the nanofilter, using a plate scanner, and counted. An overabundance of one chromosome compared to the others indicates aneuploidy.
Over the last couple of years, the Vanadis team, based outside of Stockholm, has been working closely with PerkinElmer's site in Turku, Finland — a large manufacturing and R&D facility, in particular for prenatal and newborn screening — to develop the technology into a platform, called the Vanadis NIPT System.
The company first plans to launch the system in Europe this summer after CE-IVD registration. Other countries will follow later, though the system will not be available as an IVD system in the US initially.
The Vanadis NIPT System consists of three hardware components, as well as data analysis and reporting software.
The Vanadis Extract unit is used to purify cell-free DNA from maternal plasma. On the second instrument, Vanadis Core, the chromosomal fragments are captured, amplified, and labeled. The last unit, Vanadis View, which is based on PerkinElmer's CLS High-Content Analysis system, does imaging and counting. LifeCycle software is used for analysis and reporting, building on software PerkinElmer developed for traditional prenatal screening.
"We spent a lot of time to make this a system that is very user friendly," Ericsson said. The assay has a total turnaround time of about 48 hours if 48 samples are run in parallel, of which about 2.5 hours is hands-on time, much of it related to centrifuging. The maximum throughput per run is 84 samples, which takes a little longer. A new run can be started every 24 hours, so runs can be staggered, and the system can process up to about 21,000 samples per year, assuming 250 business days.
The system is designed to be run not only by laboratories conducting complex genetic tests but also by laboratories performing more routine testing that are used to highly automated systems. Thus, it will likely be attractive to traditional prenatal screening labs that are already PerkinElmer's customers, typically biochemistry laboratories that haven't implemented NIPT to the same extent as genetic laboratories.
"We want to give our current customers the opportunity to perform screening using cell-free DNA," Ericsson said, noting that 10 million pregnant women currently undergo aneuploidy screening every year with PerkinElmer's products.
Pricing information for the Vanadis NIPT System is not yet available but costs will be competitive with existing NIPTs. PerkinElmer plans to make the system available both under a reagent rental agreement, where customers pay for each test but don’t purchase the system outright and under an instrument purchase model, Ericsson said.
At launch, the system will screen for fetal trisomies 21, 18, and 13. While it is possible to expand the content, PerkinElmer plans to stick with the main screening targets rather than try to capture as many chromosomal abnormalities as possible. "That's not what the new system is about," he said.
Meanwhile, Vanadis has been working with a number of undisclosed collaborators on additional clinical studies. One collaboration the company has publicly revealed is a clinical trial led by Glenn Palomaki, a professor of pathology at Women and Infants Hospital and the Alpert Medical School of Brown University, who was previously involved in studies of Sequenom's and Natera's NIPTs.
Palomaki said he had been looking for an NIPT that is less expensive and less involved than existing platforms. He said he had tried before to bring NIPT to his own hospital, but the equipment, bioinformatics, and license fees added up to more than $1 million, making it cost prohibitive. The reagent rental model planned for the Vanadis system, he said, "is something we believe would be advantageous for a lot of smaller laboratories to get into the business of cell-free DNA screening."
He hopes to receive the Vanadis NIPT System within the next few months and to install it in a regular laboratory. "No need for a clean room, PCR room, positive ventilation," he said, adding that the system will be operated by a research technician with no expertise in molecular testing who received training at Vanadis in Sweden.
In the meantime, Palomaki has already collected about 800 samples from pregnant women for the clinical trial to test the platform, which involves a number of sites in the US and Canada. The goal is to enroll 2,500 women from the general population and 250 women with high-risk pregnancies, and to complete the study by the end of this year or early next year.
"We believe the technology will work," Palomaki said. "What we are specifically focusing on is, 'Does it really require far less tech time? Instead of three to four techs to run 10,000 samples a year, can you do it with one tech? Does it use fewer reagents, less time to set up?'"
One downside of a less complex assay is that it is less comprehensive than a sequencing-based NIPT, which can detect microdeletions, rare trisomies, or variants that can be gleaned from a whole-genome scan. "It may be a more basic test, but at least everybody can afford it" and insurance companies may start covering it more widely, he said. "The only way to make it cheaper is to have less expensive reagents, less expensive machines, less tech time, less bioinformatics."
It remains to be seen, though, how quickly PerkinElmer will be able to establish the Vanadis NIPT system in Europe, where NIPT has already been implemented in screening programs in several countries.
The Netherlands, for example, made sequencing-based NIPT available to all pregnant women last year under the TRIDENT-2 study, using existing technology. Also, the UK approved the use of NIPT for the three main trisomies as part of an existing prenatal screening program in late 2016, and several laboratories that are part of the National Health Service there have implemented testing.
In addition, private companies in Europe have been offering NIPT at relatively low cost, often paid for by patients out of pocket, among them LifeCodexx and Cenata, both based in Germany, which offer NIPT for trisomy 21 for €200 ($247) and for trisomies 21, 18, and 13 for €300 ($370).
Besides prenatal screening, the Vanadis technology could also be used for cancer screening from cell-free DNA. "When you look at cancer applications, you need to do precise measurements and you need to detect rare events, and that's what this platform is quite good at," Ericsson said. "So, it's an interesting application," though the company is not ready to talk about its plans for that yet.