By Clay Dillow
FORTUNE -- Every year, the U.S. welcomes 4 million new babies into the world, the result of roughly 4 million pregnancies that in large part go through the same battery of prenatal health checks 4 million times: analyses of the mother's blood and urine, of the mother's blood pressure, of the mother's weight, of the mother's blood sugar -- even of the mother's genetic makeup if she's deemed a risk for certain inheritable disorders. Ultrasound imaging being the obvious exception, doctors generally measure an unborn baby's health via the mother -- a kind of science by proxy that offers only a rough approximation of the baby's developmental health.
But if parents could know more about their child's health before birth, wouldn't they want to? And if a bounty of health information -- even the unborn child's entire genome and all the data contained therein -- could be accessed via nothing more than a simple blood draw from the mother, wouldn't parents want to have that option? A handful of medical diagnostics companies think so, and a new generation of non-invasive prenatal tests (NIPT) they have brought to market over the past couple of years have positioned them to completely transform the way clinicians perform routine prenatal care -- a full 4 million times annually in the U.S. alone.
NIPT technology rests on the fairly recent discovery that a pregnant mother's blood is practically swimming with fragments of her baby's DNA, deposited there as cells from the placenta die and break down. This cell-free DNA -- so named because it is not contained within the nucleus of a complete fetal cell, but rather floats free in the mother's bloodstream -- can be identified and isolated from the mother's own DNA (it turns out cell-free fetal DNA can make up as much as 20% of the free-floating DNA in a pregnant mother's circulatory system). There are other ways to access fetal DNA of course -- Amniocentesis for instance, or the more accurate chorionic villus sampling (or CVS) test -- but these require a physical incursion into the neighborhood of the fetus itself (usually via a long needle or tube) which ups the risk of miscarriage and pregnancy-complicating infections. That's the beauty of NIPT: A sample of maternal blood, a simple blood draw, is all that's needed to access the fetal genome and all the chromosomal information it contains.
When cell-free DNA was discovered about 15 years ago, the science of genetics was not yet far enough along to make much practical use of it, but with the rapid advancement of genetic science over the past decade that's changed. Non-invasive tests can now piece together entire fetal genomes and mine that genetic information for indicators of various disorders and abnormalities that can lead to health problems later on -- things like sex chromosome abnormalities, Down syndrome, and a host of other developmental disorders. Initial trials have shown the tests to be so reliable that executives at more than one company vying for the lead in the nascent NIPT space -- companies that include Verinata (owned by Illumina (ILMN)), Sequenom (SQNM), Natera, Ariosa Diagnostics, and Ravgen -- believe their tests will become a standard, routine part of prenatal care in the next two or three years.
"When you offset something like amniocentesis against NIPT -- which is as simple as taking a blood sample -- it becomes a no-brainer," says Vijay Kumar, a health care analyst and associate managing director at International Strategy and Investing Group. "But then the question becomes cost, and given the current health care environment it becomes a much tougher discussion."
Indeed, it's cost more so than science holding NIPT testing back at this point. The tests remain relatively expensive, around $800 at the low end, and just less than $3,000 for the more expensive screening methods. Ongoing litigation between Sequenom and two other players in the space -- Natera and Ariosa Diagnostics -- has created some confusion as to who really owns what technology (not to mention some increased expense for all parties). And the technology is so new that insurers, though cognizant of the potential preventative health benefits of NIPT, have not yet determined exactly whether or how they will reimburse for the tests.
"Whether or not prenatal genetic testing becomes standard, it's certainly possible, but they're going to have to get the price point down lower than it is right now," says Les Funtleyder, a health care strategist at investment firm Poliwogg. "Managed care companies aren't rushing toward new places to spend money. If the companies in question can make the case that by doing this you're somehow improving quality or cutting costs, they could become part of standard care. But if they're adding cost onto the price of pregnancy, it won't be received enthusiastically."
That's the case the companies in this space are working to make right now. Over the past couple of years the technology has matured tremendously, with several firms bringing commercial tests to market since 2011 (a few started as paternity tests, significant in that they could determine paternity as early as eight weeks into a pregnancy). Since then, those companies have moved quickly to pile new diagnostic targets into those tests, which now screen for everything from chromosomal disorders like Down and a number of other less-notable syndromes to various sex chromosome abnormalities, many of which go undetected in young children until they are too old for hormone treatments to be effective. In the future these same NIPT diagnostics could screen for cystic fibrosis, Tay-Sachs, sickle cell anemia, and even the presence of certain genes associated with common cancers. Because the tests themselves simply extract the genetic information from the mother's blood sample, the number of disorders and genetic indicators NIPT could eventually test for is really only limited by doctors' understanding of the genome.
Yet as a diagnostic tool, these tests have largely been relegated to what are considered high-risk populations -- typically pregnant women 35 or older (for Down syndrome) or that carry some other known risk for a chromosomal disorder. But both Natera and Verinata are designing and conducting general population trials to prove their efficacy in spotting chromosomal and genetic issues in the unborn children of non-high-risk mothers -- a proposition that, if proven, could accelerate the adoption of NIPT across the board as a standard test for all pregnant mothers, something as routine as ultrasound.
The impetus for this won't be Down Syndrome or sex chromosome abnormalities, says Natera CEO Dr. Matt Rabinowitz, but NIPT's next frontier, so-called deletion syndromes. These occur when all or part of a chromosome, for whatever reason, is deleted from the genome, causing various developmental problems for the child. These syndromes aren't necessarily very well understood, but doctors know they exist and the companies in the NIPT space are confident their tests can spot them -- and will do so in their commercial version within the next six to 18 months.
"I have no doubt that this will become a front-line test across the entire population," Rabinowitz says. "And what's going to drive this to the entire population is deletion syndromes. You really want to be able to screen for these, and to be able to include these in a population-wide screen is an extremely big deal,"
That population-wide adoption will have huge public health impacts, Rabinowitz says, and he's not the only one who thinks so. The NIPT tests themselves only extract the baby's genetic information, so the only thing limiting what they can screen for is doctors' clinical understanding of the genome -- the application of that information in creating therapeutics and making clinical decisions. And with genetic science following its own kind of Moore's Law, those potential applications are growing at a prodigious rate.
"Therapeutic interventions will influence what things we test for five or six years from now," Dr. Richard Rava, vice president of research and development at Verinata, says. "There are things that are pointless to learn about right now,but in the future they very well might become relevant as therapies." When Verinata first started working on its Verifi NIPT test, Rava says, sub-chromosomal insertions or deletions -- the cause of the aforementioned so-called "deletion syndromes" -- were filed under "unknown clinical significance." Now more than 20% of those insertions and deletions are known to be connected with actual developmental outcomes for the child. What was irrelevant two years ago is already becoming relevant, and that trend will continue as geneticists connect more dots between the genome and the way it manifests itself in the body.
"There's no point in telling someone 'Your child is missing the end of chromosome 5, and we don't know what that means, so watch you child,'" Rava says. "Now we know these things have clinical relevance, and that's something people want to know. I would be shocked if this wasn't part of the test three years from now."
Still, for all of NIPT's promise, the obstacle of cost has some analysts feeling less than optimistic about the technology becoming a standard of prenatal care in the near-term. The price point has to come in below $200, ISI's Kumar says, noting that 4 million pregnancies multiplied by even just $500 is far more than the managed care industry will care to shoulder. Four or five years is a more realistic target for NIPT technology to transition from high-risk diagnostic to general population standard of care. "I think eventually this is going to be used as primary screening, I believe that," Kumar says. "But I do think it's going to take awhile."
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