By Aaron Krol
April 1, 2016 | Invitae—which began life in 2012 promising an “all-in-one” genetic test but has since become a piecemeal provider of gene panels—has launched a new series of pediatric tests, focusing on rare, high-impact variants.
Up to now, Invitae has done most of its business in hereditary cancer and cardiovascular disease. Tests in these indications, which can cover as few as a dozen or more than a hundred genes at once, search for variants that might place patients at heightened risk for serious chronic conditions, but don’t diagnose existing disease. Although it’s hard to offer clear medical advice with these kinds of risk-based tests, and although they make regulators nervous, they’ve been a popular business driver for for-profit companies like Invitae: just this week, Kailos Genetics announced a $125 hereditary cancer screen, and companies like Color Genomics and Pathway Genomics also offer tests at out-of-pocket prices.
“More and more patients are coming to their doctor, saying, ‘I’m concerned. I just learned that my uncle had this, my grandmother had this,’” says Robert Nussbaum, Invitae’s Chief Medical Officer. Like many of its competitors, Invitae prefers to deal with insurers and provider networks, but has recently made it easier for patients to order tests on their own initiative, after consulting with their doctors.
Invitae has also offered panels covering blood disorders and neurological disease.
Perhaps surprisingly, the genetic testing industry has not, historically, focused as much on rare hereditary disorders. Though vanishingly rare individually, taken together these diseases affect millions of Americans; symptoms often appear at birth or in early childhood, and can be severe and wide-ranging. Most importantly, the pathology can usually be traced to a single genetic variant. For a genetic test provider, these variants could be much easier to interpret, and far more diagnostic, than the disperse variants involved in areas like cancer risk.
Nonetheless, genetic testing in rare disease has mostly flowed through hospital labs, which might sequence patients’ whole genomes or exomes, and often take DNA samples from family members as well. That makes sense: many of the variants at issue are poorly documented or entirely new to science, so clinical geneticists need to take as broad a view as possible to track them down. But even with striking recent advances, this is an expensive and labor-intensive approach to diagnosis.
Invitae is betting that the calculus has begun to shift, as more rare disease variants, along with case descriptions, are cemented in the scientific literature. That makes it easier to build reasonably comprehensive panels tailored to specific categories of symptoms. “For a clinical exome, the charge is in the thousands of dollars,” says Nussbaum. “I believe that there are certain very clear indications for using whole genome or whole exome, but there are other clear indications for using panels.”
With the latest expansion in its test menu, Invitae is leaning much more heavily into rare disease and pediatric genetics, with new and expanded panel tests. These additions bring the total number of genes covered in Invitae tests to over one thousand, up from around 600 as of last summer. If doctors already have a good idea what category of disease a patient is suffering from, Nussbaum says, panels will be both cheaper than a clinical whole exome, and more sensitive in analyzing those gene regions that are covered.
Though the Invitae panels are preset, physicians can request some customization based on their patients’ presentations.
Invitae is also adding a related type of test to its menu: confirmatory gene panels for newborn screening. Newborns in the Unites States are routinely given a battery of tests for metabolic and immune disorders, but these tests, which need to be done quickly to offer the best care to affected children, rely on proxy measures, not genetic sequencing.
“Newborn screening is a fantastic public health triumph,” says Nussbaum. “It’s saved the lives, and protected the development, of literally tens of thousands of children. But it is a screening test, and particularly for patients who go into neonatal ICUs… the false positive rate is extremely high.” Invitae’s new gene panels are second-line tests for those infants who test positive on the first screens―the majority of whom will later turn out to be perfectly healthy. With an average turnaround time of three weeks, an Invitae test would typically be able to confirm or rule out these diseases faster than the standard of care.
Meanwhile, the company still expects that it will eventually arrive at a single, universal gene panel, as the costs of sequencing and interpreting variants continue to fall. Just this March, Veritas Genetics opened sales of a $999 whole genome, interpretation included―though it falls short of the clinical precision expected of panel tests. Increasingly, genetic testing companies find themselves competing on price and convenience, even as profits remain elusive and the FDA signals that tighter regulation is on the way.
“Our vision remains to aggregate all of genetic testing in an accessible, low-cost approach that answers the needs of patients and providers,” says Nussbaum. “But we are trying to do it in a way that is medically responsible.”