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Natera Plans Test Expansion as It Reports Clinical Data; User Details Experiences

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With the launch of its noninvasive sequencing-based prenatal aneuploidy test in March, Natera became the latest company to enter the highly competitive space, which includes first-comer Sequenom, Illumina-owned Verinata Health, and Ariosa Diagnostics.

The test has a list price of $2,750, but Natera also has a patient's assistance program to help cover costs for those who can't afford it. By contrast, Sequenom bills insurers $2,900 for its MaterniT21 Plus test and charges a $235 co-pay to patients, but offers it to uninsured women at $1,700; while Verinata's Verifi and Ariosa's Harmony have list prices of $1,500 and $795, respectively.

Natera currently markets Panorama as a screening test coupled with genetic counseling to high-risk women, but the company said that the test will ultimately be applicable to the broader population.

Seeking to distinguish itself from the competition, Panorama screens for fetal aneuploidy by evaluating SNPs rather than looking at copy number variation, which, according to Chief Technology Officer Jonathan Sheena, makes the test "fundamentally more accurate" than others. The test targets 19,500 SNPs (CSN 11/14/2012).

The most-recent clinical study, published online in April in Prenatal Diagnosis, demonstrated zero false positives and false negatives from 242 singleton pregnancies.

The study was a blinded trial of patients undergoing chorionic villus sampling, who were also screened for fetal aneuploidies using Panorama. Results were provided for 229, or 94.6 percent of the cases, and the test detected 25 cases of trisomy 21, three cases of trisomy 18, one case of trisomy 13, and two cases of Turner syndrome, with no false positives or false negatives. Additionally, the test also detected one case of fetal triploidy, a rare condition in which the genome contains three copies of every chromosome.

As a result, Natera now plans to add triploidy to its test in the near future, which will involve expanding the informatics, said Sheena. So far, no other firms offer triploidy screening in their tests.

Triploidy can have clinical implications for the mother. A woman carrying a triploid fetus is more likely to develop pre-eclampsia and has a greater risk of hemorrhaging post-partum, Sallie McAdoo, a genetic counselor at Natera, told Clinical Sequencing News. Additionally, these women are also at a greater risk for developing trophoblastic disease, rare tumors that develop in the womb.

Diagnosing triploidy will not have an impact on care for the fetus, since triploid fetuses are either miscarried or stillborn, however it could impact clinical management of the mother, including monitoring her for trophoblastic disease, said McAdoo.

Aside from incorporating triploidy screening into its test, Natera is also planning to include microdeletions and uniparental disomies. To do this, it will have to change both the number of SNPs it evaluates as well as the bioinformatics.

The company has not yet decided which microdeletions and uniparental disomies to include in a future test or when screening for such indications would be available. "You have to be careful about choosing to detect ones that are clinically relevant," said Sheena.

While Natera did not specify which sub-chromosomal alterations it was considering, other firms are also looking to add indications to their tests such as 22q11.2 deletion syndrome, which is associated with DiGeorge syndrome (CSN 5/1/2013).

Additionally, added Sheena, "uniparental disomies are interesting because they cause problems but can also expose the carrier to other recessive conditions."

For instance, if an individual inherits a cystic fibrosis allele but is UPD on chromosome 7, then they’d be missing the normal copy and would be affected with cystic fibrosis even though they only have one parent who’s a carrier, he said.

Natera did not disclose specifics on how it is faring against the other NIPT firms, but said that physician response has been "overwhelming," particularly to the company’s low false-positive rate.

One user, Martha Dudek, a genetic counselor at Vanderbilt University Medical Center, said that Vanderbilt has been testing out all options. Dudek stressed that she could not endorse any particular company's test over another, especially because the companies are continuing to update their tests, billing practices, and customer support, but said that they are all "tremendously better than the old biochemical screening."

Dudek told CSN that Vanderbilt has utilized Sequenom, Verinata, Ariosa, and Natera, but has the least experience with Verinata's test.

"Sequenom has the most experience with twins and egg donors, so if a patient met that criteria, we would likely utilize them," she said.

Nevertheless, she said that Vanderbilt uses Natera's test most frequently.

One area where Natera may have an advantage is for women with high body mass indexes, said Dudek. While she stressed that there is not yet any published literature regarding NIPT performance in overweight women, she said that evidence suggests that the amount of fetal DNA decreases as maternal weight increases, which can affect the ability of the noninvasive tests to call trisomy.

But, since Natera has "a totally different approach with their test using the SNP technology, they can work with less DNA and still get accurate results," she told CSN.

Other tests are more likely to not return a result due to not having enough fetal DNA, said Dudek. Often the companies will request a redraw, but even then the test often comes back inconclusive, which is frustrating to patients, she said.

"It's unclear whether it's individual-specific or if we can make generalizations about weight, but it's definitely true that patients over around 230 pounds are more likely to need a redraw and even after a redraw might not get a result," she said.

One area where the Natera test is not offered, though, is in cases of consanguinity. Because the Panorama test analyzes SNPs and relatives are more likely to share SNPs, the test is less likely to yield a result. In these cases, Vanderbilt will offer the patient one of the other tests, typically Ariosa's Harmony test, she said.

Going forward, Dudek said she will continue to evaluate performance data of all the tests, as well as keep an eye on changing billing practices, which could give providers a clearer understanding of patients' out of pocket costs.

"It has been a very volatile market and the products are constantly changing, so our practices have changed over time," she said.

Overall, Dudek said that there has been a "very strong uptake" of noninvasive prenatal testing at Vanderbilt.

The patient population primarily served by Vanderbilt has historically not opted for invasive testing, said Dudek, because most of the women are not considering terminating their pregnancies. However, "they seem to be wanting the information if it doesn't put the pregnancy at risk," whether it's to "be better prepared or to gain reassurance."

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