This article has been updated with additional pricing information from Invitae.
NEW YORK (GenomeWeb) – In an effort to broaden their offerings in the reproductive health market, Myriad Genetics and Invitae last week both announced new or expanded genetic noninvasive prenatal screening tests for fetal chromosomal aneuploidies.
With these tests, the companies have entered an already crowded US market, with a dozen or so laboratories offering similar NIPTs. The tests are currently covered by most health insurance plans for high-risk pregnancies but only by some for average-risk pregnancies, though market observers expect this to change in the future, in particular if the American College of Obstetricians and Gynecologists fully endorses NIPT for screening in all-risk pregnancies.
Both companies' tests — Myriad's Prequel Prenatal Screen and Invitae's Non-Invasive Prenatal Screening (NIPS) — rely on whole-genome sequencing and are based on technology patented by Illumina and Sequenom. The firms say they are differentiating themselves from competitors by offering, for example, information on additional disorders, bundling their tests with genetic carrier screening, including genetic counseling, or providing low-cost options for patients not covered by insurance.
However, some say their tests are not all that different from what is already available, arguing that what is really needed for broad insurance coverage is a test that can compete in cost with current first-trimester screening.
The US market for NIPT has been growing steadily over the past few years. In 2018, an estimated 1.2 million tests were conducted in the US, a number that is expected to grow by 10 to 20 percent annually through 2020, according to DeciBio Consulting, a Los Angeles-based firm that specializes in precision medicine. Most of these tests were conducted by large centralized laboratories.
Among the major NIPT testing labs in the US are Natera; Ariosa Diagnostics, which is part of Roche; Laboratory Corporation of America, which acquired Sequenom in 2016; Progenity; Mayo Clinic Laboratories; and ARUP Laboratories. In addition, Illumina offers its Verifi test as a service to partner laboratories. Illumina and Sequenom, as well as Natera, have both licensed their respective NIPT patent portfolios and technologies to other labs.
Myriad said last week that its Women's Health subsidiary is now offering an expanded version of the firm's Prequel Prenatal Screen that includes aneuploidies of all chromosomes instead of just chromosomes 13, 18, 21, X, and Y.
According to Jim Goldberg, chief medical officer of Myriad Women's Health, the additional aneuploidies are individually rare but have an incidence of about 1 in 200 in aggregate. "We feel that now, there is sufficient data linking those rare autosomal aneuploidies with adverse perinatal outcomes, and we think it's important to make that information available," he said. Test results include rare aneuploidies that may be confined to the placenta, which could lead to pregnancy complications.
Myriad's test is not the only one to cover all aneuploidies, though — Illumina's Verifi Plus Prenatal Test, for example, also includes those.
The company did not reveal pricing for the test, which it primarily offers in the US, but said it is in network with most major insurance plans and offers financial assistance to patients with a high deductible or who are not covered by insurance. The firm said it provides patients with personalized price estimates, based on their insurance and clinical indication, and the average out-of-pocket cost for patients is $154.
Myriad originally obtained the Prequel Prenatal Screen test through its acquisition of Counsyl last summer, where Goldberg used to be chief medial officer. Counsyl had developed the test based on IP it licensed from Illumina and Sequenom. It had initially outsourced the testing to Illumina before launching its own test in 2014, first called Informed Pregnancy Screen and later renamed Counsyl Prelude Prenatal Screen.
Goldberg said that since the acquisition, Myriad has made several improvements to the test. Last year, for example, it changed the methodology to be able to detect trisomies with higher accuracy in patients with a fetal DNA fraction below 4 percent. He added that details of this new method will be disclosed in a forthcoming publication.
In addition, the company is working on a new microdeletion panel that will have increased accuracy and thus improve the positive predictive value of the test, Goldberg said. He declined to reveal details of the approach at this point and said there is no timeline yet for the launch of the panel. However, during Myriad's earnings call last week, Myriad CEO and President Mark Capone said the new microdeletion panel "leverages our substantial intellectual property developed from hereditary cancer testing."
The Prequel test already reports results for five types of microdeletions, and competing NIPTs from other companies, including Natera, LabCorp, and Illumina, also cover microdeletions. However, studies have shown that the false-positive rate of NIPTs for microdeletions and microduplications tends to be high, and that some are missed.
Goldberg said that in addition to improvements to the test itself, Myriad distinguishes itself from competitors through support services — through an application called "Myriad Complete" — including pretest education, cost estimates, a detailed report explaining the results, and access to genetic counseling, which he said is something Counsyl was already known for.
He also said that healthcare providers will likely appreciate being able to order carrier screening — Myriad's Foresight test, which also originally came from Counsyl — and NIPT from the same laboratory. However, obstetrical care providers often do not have a choice which lab to order a test from because their patient's insurance might only cover a test from a specific provider.
Myriad's prenatal sales force, which the company tripled in January and which it says is larger than those of its competitors, will continue to promote both tests.
Invitae, likewise, now offers both carrier screening and noninvasive prenatal aneuploidy testing as part of its reproductive health portfolio. In 2017, the company obtained carrier screening capabilities through its acquisition of Good Start Genetics. In addition, Invitae provides invasive diagnostic prenatal testing, which resulted from its 2017 acquisition of CombiMatrix.
Last week, Invitae announced the launch of NIPS — the company prefers the term NIPS over NIPT in order to stress that it is a screening test, not a diagnostic test — which covers trisomies 13, 18, and 21 and includes microdeletions and sex chromosome aneuploidies as an add-on.
According to Invitae Chief Medical Officer Bob Nussbaum, the company is initially outsourcing the testing to Illumina, which will run its Verifi test for Invitae, but has plans to bring the test in house eventually, though there is no timeline yet.
The reason Invitae chose Illumina's test technology, he said, is that it has the lowest failure rate among all NIPTs and because it relies on whole-genome sequencing, which Invitae is very familiar with. "It's something that we feel extremely comfortable with and expert in," he said.
Also, sending the NIPS out to Illumina at first enabled the company to broaden its reproductive health menu quickly, allowing it to keep up with competitors Myriad and Natera, which also offer both carrier screening and NIPT. "We really acted with a sense of urgency once we started offering our carrier screening to be able to bring an NIPS option in house quickly," said Invitae Chief Commercial Officer Katherine Stueland.
It also helped Invitae to stay with its mission to "provide genetic testing for any and all indications," Nussbaum said, which it sees as a competitive advantage. "The idea is that we will be a one-stop place for women’s health and reproductive health," he added, an area where the company now offers carrier screening, noninvasive prenatal screening, invasive prenatal testing, preimplantation genetic testing, and gynecological cancer risk assessment.
Invitae will also offer NIPS together with its Invitae Carrier Screen, using a single specimen collection kit, though Nussbaum said that the company's "vast preference would be to do [carrier screening] preconception" instead of during pregnancy, which would require two separate samples.
Another way Invitae is differentiating its noninvasive prenatal test is through pricing. The list price for NIPS is $2,500. However, the company is in network with payors covering more than 280 million individuals, and in-network pricing ranges from $360 to $800, according to Stueland. For those who are not able to get the test through their insurance, or who have a high co-pay, it offers a patient-pay price of $250.
Because NIPT is currently not universally covered for average-risk pregnancies, "we feel very strongly, as we have in every other area of genetic testing, that there ought to be a patient-pay option that is reasonable enough" for patients to pay out of pocket, Nussbaum said.
However, some experts believe neither Invitae's nor Myriad's test changes the current NIPT landscape much and that in order to make NIPT accessible to all women, a low-cost test is needed that can be reimbursed by insurance at a similar rate as current first-trimester serum screening, on the order of $200 to $300.
"It is interesting that these two new large companies are joining the fray of more than a dozen companies offering [NIPT] in the US," said Glenn Palomaki, a pathology professor at Women & Infants Hospital and the Alpert Medical School of Brown University, who has collaborated with several NIPT test developers in the past, including Sequenom and Natera. "They each have some advantages, but what is really needed, I believe, is to have the cost of testing come down."
Rather than covering rare disorders, like microdeletion syndromes and rare chromosomal aneuploidies, which can yield results that are difficult to interpret and may not provide clear actions to take, "the focus needs to be on the real reason we’re doing screening, which is Down syndrome," he said. "Bring the cost down, so it can be made easily available to all pregnant women."
At Women & Infants Hospital, Palomaki is involved in an ongoing study of PerkinElmer's Vanadis test, which only screens for trisomies 13, 18, and 21, relies on targeted DNA amplification and fluorescent imaging rather than sequencing, and aims to reduce the price of NIPT to around $100. Earlier this year, PerkinElmer said that the system, which obtained CE-IVD marking last year and is already sold in Europe, is not yet available in the US.