Following the US Supreme Court's decision two weeks ago to strike down Myriad Genetics' central patent claims to the BRCA1 and BRCA2 genes, several US genetic testing laboratories have been gearing up to snatch a piece of the BRCA testing market in this country, previously Myriad's monopoly.
At least three laboratories — Ambry Genetics, DNA Traits, and Ethigen — are already accepting and analyzing samples from US patients, while a number of others, including Emory Genetics Lab, GeneDx, Pathway Genomics, and Quest Diagnostics, are preparing to launch their tests later this year (see table at bottom of article).
Some of the tests focus exclusively on the BRCA genes, thus competing directly with Myriad's BRACAnalysis test. Others include BRCA1 and BRCA2 as part of hereditary cancer gene panels, some of which will likely compete with Myriad's 25-gene myRisk Hereditary Cancer panel, which the company plans to launch later this year.
Customers will compare the new BRCA tests with Myriad's offerings in terms of price, turnaround time, and quality of the results, including the variant-of-unknown-significance, or VUS, rate.
Prices for the new tests currently range from $500 for a deletion and duplication-only analysis of the BRCA genes, to $995 for a sequence analysis of the two genes, to $5,830 for a comprehensive hereditary cancer panel that includes 24 genes. Their turnaround times vary from two weeks to four months.
In comparison, Myriad's BRACAnalysis test has an average private insurance cost of $3,100 and a turnaround time of less than 14 days, and its BRACAnalysis Large Rearrangement test costs an additional $580. Medicare prices are $2,795 and $587, respectively. The myRisk Hereditary Cancer panel will have a list price of $4,000 to $4,500, with a turnaround time of two weeks or less, according to the company.
Myriad told Clinical Sequencing News via e-mail that it is "committed to offering the highest quality BRCA test, fastest turnaround time, and best customer service in the industry," noting that "BRACAnalysis is the leading test for hereditary breast and ovarian cancer and has been used by more than one million women."
The company said its test is "widely accessible and reimbursed" by health insurance, and that most patients can receive it with no co-pay or deductible because it is covered under the Affordable Care Act. In addition, Myriad said it offers free or subsidized testing to patients "depending on their level of need."
Myriad also pointed out its large proprietary database of more than 14,300 variants and its low VUS rate of 2.5 percent for BRACAnalysis.
New market players for BRCA testing
But the competition is mounting. "We've been waiting for this day for years," said Ardy Arianpour, senior vice president of business development at Ambry Genetics, which launched its new tests the day of the Supreme Court decision. "We always knew we wanted to do BRCA1 and BRCA2 via next-gen sequencing if the patents fell."
Ambry has been offering hereditary cancer panels for almost two years — it currently offers BreastNext, CancerNext, ColoNext, and OvaNext panels — during which time it has analyzed several thousand patient samples.
Several of these panels have always included the BRCA1 and 2 genes for R&D purposes, but the data were masked during the analysis. "We had it, but internally, nobody knew that we had it and we never reported it out," Arianpour said. "But now, we can go back and we have all those data — that's very important for us."
Ambry currently offers several tests that include the BRCA genes, all of which use Illumina's next-generation sequencing platforms, either the HiSeq or the MiSeq. The tests include a BRCA1/2 test that analyzes both DNA sequence and deletions and duplications; a deletion/duplication-only version of the same test; a small panel that includes BRCA1/2 as well as four other genes; and the larger BreastNext, OvaNext and CancerNext panels. While some of these tests utilize the RainDance platform to amplify the DNA for sequencing, the company also uses two other enrichment methods.
The company has already accepted samples for testing and will return the first results shortly. "Right now, we're being flooded with samples," Arianpour said.
Ambry does anticipate reimbursement for its tests. "We have many contracts with multiple insurance providers," he said.
In anticipation of increased demand for its BRCA1/2 and other hereditary cancer panels, Ambry is more than tripling its testing capacity at the moment, which includes additional sequencing instrumentation.
It is also working on reducing the turnaround time for its BRCA1/2 sequence and duplication/deletion test from a current 21 days to between five and 13 days, which would make it competitive with Myriad's turnaround time.
Ambry expects its VUS rate for BRCA to be "similar to those of other large, well-studied genes," Arianpour said. The company uses both publicly available databases and data from unnamed external collaborators to interpret variants.
Overall, the company appears to feel confident about being able to break into Myriad's market and plans educational programs and webinars to promote its new tests.
"There is a lot of backlash against Myriad, and we are feeling the upside on that," he said. "I can't tell you how many phone calls are coming in, stating that they want to send us samples."
Ethigen, like Myriad Genetics, is based in Salt Lake City and also is already offering next-gen sequencing-based BRCA testing, contracting the work out to an undisclosed academic laboratory in the UK.
The company was founded in early 2012 by Eric Dyer, a former Myriad employee who used to be head of marketing for the firm's colon cancer products.
"For a long time, I had a vision for a different type of genetics company — a company that was much more in service to the genetics professionals, much more actively trying to deliver the best prices possible, and above all else, was able to bring an alternative for BRCA testing to the US," Dyer told Clinical Sequencing News.
Ethigen collects patient samples and sends them to a CLIA- and CAP-certified hospital-affiliated laboratory in the UK that "probably second to Myriad, has the most experience with BRCA sequencing in the world," he said. The reason he does not want to disclose the partner is to prevent it from getting "inundated with questions and direct contact."
The lab, which uses Illumina's sequencing platform for the analysis, sends the test results back electronically, which Ethigen reports back to the ordering healthcare provider, so far exclusively genetic counselors. Ethigen also handles billing for the test, which includes BRCA1 and 2 as well as an optional 17 other genes at no additional cost. The test costs $2,495 and has a turnaround time of 28 days.
Coverage of the test by health insurance "will vary greatly from payor to payor, and even case by case within the same plan," Dyer said. He said he expects payors to cover claims at in-network rates initially, and "each laboratory will need to determine what level of risk it is willing to take with reimbursement and develop strategies to help patients manage any out of pocket fees."
Ethigen confirms benefits prior to testing and discusses options with patients if their exposure will be higher than 10 percent of the cost of the test. In addition, it offers "payment terms" for individuals unable to cover the out-of-pocket expense and discounts for patients who pay in full at the time of testing.
Dyer said the company has been providing BRCA testing internationally since earlier this year, "on a fairly limited scale," and has now also started sending out samples from US patients.
Ethigen plans to remain focused on genetic counselors and other genetics professionals "who truly wanted an alternative to Myriad, either because they want a broader analysis, which we offer, or because they just want a better price," Dyer said. "We are not looking to be the next big genetics lab."
DNA Traits, a division of Gene by Gene, meantime, offers a Sanger sequencing-based BRCA1 and 2 test, which it launched in the US immediately after the Supreme Court decision. It has been offering the test internationally for more than a year, primarily in Europe and Israel, though volumes have been low, according to Bennett Greenspan, the firm's managing partner.
The test, which runs on ABI 3730 machines, has a list price of $995 and a guaranteed turnaround time of four to six weeks, though turnaround is currently only three weeks and is expected to decrease as the company gains more experience. The test does not include a rearrangement analysis at the moment, but the company plans to add that within a month. DNA Traits does not currently offer a mechanism for taking health insurance.
Once volume for the test builds up, the company plans to switch it over to a next-gen sequencing platform. The firm currently has several MiSeq and HiSeq instruments installed, which it uses for mitochondrial, exome, and genome sequencing.
As the market for BRCA testing becomes more competitive, prices will likely go down in general, Greenspan said. "All those people who don't have insurance or where insurance will not cover them for a $3,300 test now have the opportunity to order a test and pay for it themselves, paying a whole lot less than they would have paid previously."
Building new variant databases
Like other testing labs, DNA Traits uses freely available databases to interpret BRCA variants, but over the coming years, Greenspan believes efforts to build public databases with patient-supplied results will level the playing field with Myriad.
"According to the Supreme Court, [Myriad was] able to build up [its database] under the protection of a patent when the patent was issued incorrectly," he said. "I think the onus should be on them to share that data for the benefit of humanity, and if they are not going to do that, I'm sure over the next year or two, with many other labs providing such a test, all those mutations that they've seen which are not well-known will become well-known, for the benefit of the general public."
According to Dyer, "there is little question that for the time being, [Myriad's VUS rate] will be best in class." Ethigen's own VUS rate for BRCA analysis, for example, is currently around 10 percent, or higher with additional genes, but "as we only work with certified genetic counselors, we feel that they are well-equipped to discuss the potential for VUS results in the expanded panel with their patient, helping them to reach a decision that balances their personal family history of cancer and desire for information with the potential for an uncertain result."
According to Sherri Bale, managing director at GeneDx, Myriad's VUS rate "is actually unknown" because it has been many years since the company published data showing how frequently they are able or unable to classify a variant. She said the Sharing Clinical Reports Project, which aims to collect information on BRCA1/2 variants and make them publicly available in the NCBI ClinVar database, "is providing an incredible resource," both for BRCA and for other clinically relevant genes. "It will be only a short time before the labs that are doing BRCA1/2 testing have a public database with variants that will rival or surpass Myriad’s private one."
Legal obstacles left?
Following the Supreme Court's unanimous decision to strike down five of Myriad's patent claims on isolated DNA, Myriad said in a statement that it still has "more than 500 valid and enforceable claims in 24 different patents conferring strong patent protection for its BRACAnalysis test," in particular method claims and claims on cDNA.
Despite those claims, many US testing labs now seem to feel safe offering BRCA testing.
Ambry's Arianpour said his company had several independent high-level patent lawyers review Myriad's patents and concluded that none of its new BRCA tests infringe them. "There is nothing being infringed whatsoever," he said.
According to GeneDx's Bale, Myriad's claims on cDNA are "completely and totally irrelevant to the testing we and other diagnostic labs are doing," because those tests do not produce or use cDNA.
"The material that is used is naturally occurring DNA that is simply isolated from an individual’s cells and then sequenced directly," she said, a product of nature that the Supreme Court found to be ineligible for patenting. "Any chatter from Myriad (or others) to the contrary is pure spin."
"I'm sure that if Myriad has other patents that they feel are being violated, they will do what any company does," said Greenspan. But, he noted, many labs are now launching BRCA tests. "Are all of us reading this incorrectly? I don't think so."