NEW YORK – Over the next year, labs offering Illumina's next-generation sequencing-based noninvasive prenatal testing solution can expect an upgrade — whether they want it or not.
Though it will be "kind of a mandated upgrade," Illumina Clinical Genomics Product Marketing Manager Amit Patel said, the firm doesn't foresee any issues in getting customers to roll over to the VeriSeq NIPT solution v2. "The performance is so much better and you get additional menu, so there's a pretty big incentive" to change, he said. New genome-wide screening options include aneuploidy information for all autosomal chromosomes and some copy number variation aberrations.
The solution is designed to run on the NextSeq 550Dx, Illumina's clinical-grade sequencing instrument, which could help drive reimbursement and open new markets for NIPT. And an additional kit that runs just 24 samples offers flexibility to a range of customers.
Illumina has collaborated with Australia's Victoria Clinical Genetic Services (VCGS), a nonprofit clinical lab associated with the Murdoch Children's Research Institute, to validate v2 with a clinical study of more than 2,300 samples.
"I'm a very firm believer in a genome-wide approach" to NIPT, said Mark Pertile, deputy laboratory director at VCGS and head of the Division of Reproductive Genetics. "Certainly we try to differentiate ourselves from other services and v2 helps achieve that. But our primary aim is to provide the best possible screening test we can for women who are trying to determine whether their pregnancy is at increased risk of a serious chromosome condition." VeriSeq V2, he said, helps achieve that, too.
His NIPT lab, which has been doing genome-wide screening for several years using non-VeriSeq software for analysis, is one of several to have already been upgraded. Previously, his lab had been using a single-end sequencing version 1 assay, albeit on an unautomated installation. They still do some analysis beyond what the VeriSeq v2 software provides, but Illumina's solution handles all their samples. "Overall, it's been very successful and surprisingly easy," he said.
VeriSeq NIPT v2 launched in June, and took about a year and a half to develop, Patel said. Like its predecessor, the VeriSeq NIPT solution v2 provides information about trisomy 21, 13, and 18, as well as some sex chromosome aneuploidy. It still offers an automated, next-generation sequencing-based workflow that can process up to 96 samples in about a day, with PCR-free library preparation.
But it also includes options for looking at other autosomal aneuploidy and some copy number variation (CNV) aberrations, namely partial deletions and duplications larger than 7 megabases.
Adding these detection capabilities doubles the amount of abnormalities the platform can detect, Patel said. In average risk populations, the three main trisomies — 13, 18, and 21 — have about the same prevalence as all the other autosomal chromosomes together. By including these and CNVs, the test "almost doubles the diagnostic yield," Patel said.
Pertile said that switching between the basic and genome-wide screening modes is as simple as flipping a switch. He suggested that many women, especially in certain parts of the world, might choose to screen for just the more common trisomies, so that choice was valuable.
"I think that once a lab starts screening genome-wide, it does lead to a situation where some results become more complex," he said. "My one caveat is that labs offering these tests should have personnel with a good understanding of what these results mean clinically and also the complex biology behind them. It can be a plug-and-play test, but I think having knowledgeable and well-qualified staff is important as well."
Illumina has also introduced a new kit that runs only 24 samples, which could be a boon to both smaller labs and labs that want quicker turnaround time. "Now you don't have to wait to batch samples," Patel said. "And you can get results back to the patient quicker."
In several ways, Illumina sees v2 as a way to drive NIPT acceptance around the world. Developed for Illumina's clinical-grade instrument, rather than a research use-only sequencer, VeriSeq v2 can now reach markets that require in vitro diagnostic regulatory approval, like South Korea and Saudi Arabia, Patel said. This, he added, could also advance reimbursement from payors.
And Illumina hopes that it can show increased value to NIPT testing with the new platform to help drive up testing numbers. "At this point, in Europe, we're at less than 15 percent of pregnancies [getting screening]" said Tina Amirkiai, a public relations manager at Illumina. "Hopefully this is going to help us move that needle."
Illumina hopes the performance data from the VCGS trial will also help drive acceptance.
For Trisomy 21, 13, and 18 VeriSeq v2 offers sensitivity of greater than 99.9 percent and specificity of 99.9 percent. The previous version offered similar specificity, but sensitivity of 98.9 percent for trisomy 21, 90 percent for trisomy 18, and 100 percent for trisomy 13.
Sensitivity for other autosomal aneuploidy was 96.4 percent, with specificity of 99.8 percent; for CNV aberrations, 74.1 percent sensitivity, with specificity of 99.8 percent.
Total failure rate was 1.2 percent, Pertile said, and of those, many were due to iFact, the individualized fetal aneuploidy confidence test, an internal quality control indicating sufficient sequencing coverage and data quality for a given fetal fraction. He noted that failed samples in the study were not re-run, which would likely happen in clinical practice.
"What we really wanted to do was make sure we were gearing ourselves towards high specificity, to avoid the possibility of false negatives, as this is a screening assay and not a diagnostic assay," Patel said. "We were able to accomplish that." He added that the sample number was in line with what a clinical lab might see each year in routine testing practice.
Data from the VCGS study have not yet been submitted for peer review, although Pertile said Illumina plans to do so.
At the time of launch in June, VeriSeq v2 was available in a number of European countries, including Germany, France, and the UK, as well as South Africa. Patel said that since then, Illumina has received registration in Australia. The firm expects to get the product registered in Israel in the fourth quarter of 2019 and is also expecting registration in New Zealand.
Patel said that the Netherlands, where VeriSeq v2 is approved, already offers testing for all autosomal aneuploidies as well as some CNVs using a different software package. When those labs upgrade they will transition to using VeriSeq v2 for those analyses. He also suggested that Illumina is awaiting news from Germany about its plan to provide coverage for NIPT for high-risk pregnancies.
Reimbursement is "moving towards the expanded panel," but remains mostly for the basic screen of chromosomes 21, 13, and 18, he said. Where payors are already reimbursing for the prior version, they will "automatically reimburse the v2 assay as well," he said.
But Pertile estimated that even in Australia, where there's no funding for NIPT, more than 1 in 4 pregnant women are electing for NIPT. "There's been very high demand for it," he said.
Patel said Illumina wanted to have 95 percent of its VeriSeq customers converted by June 2020, as it does not want to have two different platforms on the market at the same time in the same countries. The process is "pretty invasive," he said. "The actual conversion is pretty lengthy. It takes four to five days for our field personnel to go out to the customer, upgrade the software, do some hardware upgrades, and run test protocols to make sure everything is running well."
He said that customers should plan ahead to schedule the upgrade and be ready to halt or delay delivering results for the duration.
But Illumina has already converted five customers in the last two months, he said, "and they've gone pretty well."