During the San Antonio Breast Cancer Symposium last week, InVitae announced the commercial launch of a 29-gene next-generation sequencing test that doctors can use to learn their patients' risk for hereditary breast and ovarian cancer, but also a number of other hereditary cancer syndromes.
In launching this test, InVitae will compete with a number of firms marketing hereditary cancer panels, but most directly with Myriad Genetics, the leading provider of BRCA mutation testing associated with heightened risk of familial breast and ovarian cancer (see related story, in this issue). While doctors ordering Myriad's myRisk panel will learn at once whether patients carry variants in any of the 25 genes gauged by the test, InVitae is taking a staged approach toward reporting additional hereditary cancer-risk variants to doctors and patients.
In addition to performing full gene sequencing, as well as deletion and duplication analysis of BRCA1/2 genes, InVitae's test analyzes six genes linked to high familial breast cancer risk; 18 genes associated with hereditary breast, ovarian, and endometrial cancers; and 29 genes in total that play a role in hereditary cancer syndromes. Physicians can order the full panel or they can start with the BRCA1/2 test, and then, if there is a family or medical history suggesting the need, they can learn if a patient has mutations in other cancer-associated genes in InVitae's broader panel.
The price for the BRCA testing is $1,500 and the turnaround time is two weeks, according to InVitae. Should the doctor decide to learn about the additional gene mutations harbored by the patient beyond BRCA1/2, InVitae will report those to the doctor at no additional charge.
"What we're offering the physician is a go-at-your-own-pace option," InVitae CEO Randy Scott told PGx Reporter at SABCS. "If you just want BRCA, just order BRCA. If you want the entire hereditary caner syndromes panel, order that. If you want to customize the panel, select any subset of these genes."
InVitae is taking this gradual approach to reporting genes beyond BRCA through its testing service recognizing that physicians may not think that certain genes are ready to be used in risk stratification, and patients may not be ready to learn what additional cancer risks they harbor. "We're actually finding that in the medical community, there's a lot of debate about the value of the different genes," Scott said.
Earlier this year, the American College of Medical Genetics and Genomics sparked much debate among researchers and healthcare providers when it recommended that labs conducting clinical exome or genome sequencing should examine a list of disease-linked genes and return those results to ordering physicians, regardless of whether they asked to see data on these markers. The organization's list includes mutations in a variety of genes strongly linked to diseases such as hereditary breast and ovarian cancer, Lynch syndrome, and hypertrophic and dilated cardiomyopathy. The guidelines raised significant debate in the life sciences sector, however, about the ethics of reporting this information versus not reporting it.
"We're trying to be flexible … and not put physicians in a position of having a lot of data on a gene that they're not sure about, but now, the patients has seen the report," Scott said. "We're really trying to maximize the flexibility to the physician and the patient."
Whether doctors and patients want to know the results or not, genetic testing is moving toward the use of multi-gene panels to lowers costs and increase efficiencies. And as such, they will have to contend with much more information about disease-linked gene variants than they've had to previously.
In this environment, InVitae's plan is to continue to do studies to elucidate the relationship between genes and illness. In a 200-patient study with Stanford University, researchers from InVitae reported in September that its NGS panel picked up 21 "potentially pathogenic" variants in genes other than BRCA1/2, including ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4. Of these patients, 14 had variants that had implications for their care and they were recommended for confirmatory testing and counseling.
For example, a 45-year-old woman with a deleterious MLH1 mutation received a colonoscopy, which identified a tubular adenoma that her doctors subsequently removed. Based on the results of InVitae's test, this patient received a colonoscopy five years before it would have been recommended for her according to existing guidelines.
"This field is moving very, very fast, and guidelines are going to be outdated rapidly as we get more and more information around genes," Scott said. "It's a well-established fact that less than half of hereditary breast cancer is accounted for by BRCA1 and BRCA2. The remaining portion is a variety of other genes that are not as prevalent but as an aggregate contributes much to risk.
"We think as we generate more data … we'll all learn more about what's appropriate for different populations," he said.
However, InVitae has more work ahead in its bid to cultivate more data around its test and about the ever-growing list of rarer and rarer gene markers implicated in cancer risk. Currently, in terms of BRCA genes, InVitae reports that its NGS test panel has 100 percent analytical concordance and 99.8 percent agreement of clinical interpretation compared to testing performed by Myriad, considered the industry standard. The company also claims that its NGS test panel has a BRCA1/2 variants of unknown significant (VUS) rate of 6 percent.
To date, InVitae has data from 700 samples currently informing the BRCA1/2 VUS rate for its NGS test. Scott said that the company is hoping to analyze 1,000 samples by early next year.
Although Myriad and InVitae's NGS panels highlight the importance of testing genes beyond BRCA1/2, Myriad's 1 million variant database and less than 1 percent VUS rate for BRCA mutations for myRisk is an advantage that competitors like InVitae will have to contend with for the near term. Myriad officials are aggressively highlighting to customers and payors its market experience with BRCA testing and low VUS rate compared to competitors.
During an investor meeting at SABCS, Myriad officials discussed an instance where an unnamed lab reported that a patient had a pathogenic BRCA variant. Based on the report, this patient got a prophylactic mastectomy but then found out some weeks later from the lab that the variant was benign.
Some experts in the field have proposed that in the current environment, as multiple test providers have entered the market, patients should receive testing from a reliable lab that provides BRCA testing at a discount to Myriad's service. Then, if the test picks up a pathogenic mutation, then the patient should confirm the presence of that specific marker with Myriad's test.
In Scott's view, a competitive marketplace is one that ultimately ends up bringing patients higher quality healthcare products. "The advantage of having multiple companies in this space and why we're very much against gene patenting is that you have access to a variety of tests [and] you can get second opinions," he said. "That's valuable. Our goal should be to get the most accurate information for patients and put patients first. So, we're quite comfortable that there are going to be multiple players in this space [and] different qualities of tests."
Scott also wasn't shy about addressing the lawsuit that Myriad brought against InVitae in late November and the countersuit his company volleyed at Myriad. InVitae is one of six test developers performing BRCA testing that Myriad has sued alleging patent infringement since the Supreme Court this summer found several of its claims on isolated BRCA sequences patent ineligible and upheld certain claims on cDNA.
"The lawsuit is a really important precedent-setting case that's much, much bigger than BRCA. I would say that lawsuit doesn't have a lot to do with BRCA at all," Scott said. In legal documents, Myriad has charged that competing labs infringing its patents may be providing testing at a discount to its tests but they are also providing lower quality testing. In doing so, these labs are placing patients' health at risk, Myriad believes.
For InVitae, these lawsuits are critical for growing patients' access to accurate and cheaper testing. Myriad's myRisk panel carries a list price of around $4,000.
"What we want to do as a company … is defend individuals' rights to get access to their own naturally occurring genetic information. … So, we think it's important once and for all to knock out this kind of patenting or it will affect the status of this whole industry for decades," Scott said. "For us this is a really important … case about individual freedom and about access to information that affects not just individuals but entire families."
Ultimately, InVitae's goal is to aggregate testing for the more than 3,000 known Mendelian genetic disorders into a single assay. Over the summer, InVitae began offering to early access customers a 211-gene panel that addresses 260 conditions. The NGS test screens for 101 carrier conditions, 53 neurological disorders, 80 cardiovascular diseases, and 50 cancer-related illnesses. In one year's time, the company hopes to expand the platform to test for genes associated with more than 1,000 conditions for less than $1,000.