Inside the Diagnostics Industry: BRCA Testing Growing; Market Increases Seen With New Players, Intended Populations

The 2013 revelation of Angelia Jolie’s BRCA status and the U.S. Supreme Court’s ruling invalidating the patentability of the BRCA gene the following month thrust BRCA testing into the limelight. Already recognized in clinical circles as perhaps the most prominent example of how knowledge of genetic variants can be used to reduce disease risk, the high-profile status the BRCA gene garnered in lay media increased public awareness of genetic testing and its potential implications. Given the anniversary of both of these events, DTET examined how BRCA testing has changed over the course of the past year and how the rapidly expanding market will evolve in the coming years. The most immediate implication of the Supreme Court’s unanimous decision against gene patenting in June 2013 was competition for Myraid Genetics (Salt Lake City), which had previously held exclusive testing rights for all BRCA testing in the nation. Not only did other laboratories, such as Ambry Genetics and GeneDx, immediately begin offering a BRCA test, but additional entrants have entered the market throughout the year, including national laboratories LabCorp and Quest Diagnostics. Competition “BRCA testing now has quite a lot of competition,” Amanda Murphy, an analyst with William Blair & Co., tells DTET. While intellectual property litigation is ongoing, Myriad has no IP protection and if they do, the other companies believe they can work around it. You now have a free-for-all.” Competition is entering the marketplace in many forms. For some laboratories, BRCA testing is their first next-generation sequencing (NGS)-based test, while others have NGS experience but now have the freedom to offer the test or to add the mutation to panels. CLIA-certified Counsyl (San Francisco) became one of the newest entrants in the BRCA market with its May announcement of the launch of its Inherited Cancer Screen. The company, however, was not new to NGS-based testing as it had adopted the upgraded platform for its Family Prep Screen test. “We had already booted NGS as a platform doing our Family Prep Screen, a recessive carrier screening test. So we were comfortable with it to move into inherited diseases, and BRCA was fairly natural, given our patient experience,” Eric Evans, a co-founder and chief scientist at Counsyl, tells DTET. “We began development before the Supreme Court announcement because it was seeming obvious the direction it was headed.” Evans characterized the uptake of the test as “fairly substantial.” The company also announced it raised $28 million in Series D financing that will further expand commercialization of the inherited cancer test, which the company offers for $999 (cash price), substantially lower than the $3,000-plus price tag for Myriad’s BRACAnalysis test. Declines in BRCA test pricing have been heralded by patient advocates as one of the advantages of an increased number of players in the market. Medicare will reimburse the test at a rate of $2,184 in 2015, substantially lower than Myriad’s historic price. Private payers are also noticing cost and emerging evidence shows that they will direct testing volumes. In late May it was reported that two insurers (Horizon Blue Cross Blue Shield of New Jersey and Amerigroup) independently notified health care providers in their networks to discontinue using Myriad for BRCA testing and to rely instead on in-network laboratories for BRCA testing. In addition to a broad financial and competitive impact, Murphy says that the Supreme Court decision has caused diagnostics industries to question their intellectual property (IP) positions. “Composition of matter claims had traditionally been stronger than method claims, but it didn’t hold up,” explains Murphy. “Generally, the strength of IP to protect a market position has gone down and companies must differentiate in other areas, like with harder to replicate clinical data. Generally publication of validity and clinical utility becomes the mode, rather than IP.” Murphy stresses that the technical component is not the biggest challenge in launching BRCA testing. The more difficult aspect is understanding the clinical significance of variants. This is where, despite efforts to construct a public database, some believe Myriad maintains an advantage with its vast proprietary database. However, with the trend toward panels, rather than single-gene tests, Myriad’s advantage dwindles. Increasing Use of Panels The Supreme Court’s decision permits the inclusion of BRCA analysis in broader, inherited cancer panels that are permeating the commercial market. This trend toward higher complexity is one that industry experts expect to continue, especially as the cost of sequencing continues to decline. The outstanding question is how many clinically relevant variants should be included. In the midterm it is believed targeted panels will be preferred over whole-genome and whole-exome sequencing due to the ability to limit analysis to actionable genes. Even Myriad is migrating its BRCA testing away from the BRACAnalysis test to its myRisk panel. The NGS panel analyzes 25 genes associated with eight hereditary cancers, including breast, colon, ovarian, endometrial, pancreatic, prostate, and gastric cancers, and melanoma. Payers are showing early commitments to migrating to these panels. Early in May, Myriad signed a three-year deal with UnitedHealthcare for coverage of Myriad’s myRisk panel for beneficiaries who meet certain eligibility criteria for hereditary cancer risk. Murphy says it is encouraging that a large payer sees benefits from testing additional genes. She says the agreement even allows for incremental gene testing in previously tested patients. Myriad called the agreement “transformational” and said it was the first major coverage decision by a payer for a multigene panel. Future Testing Without a doubt the “Jolie dilemma” boosted BRCA testing volumes, and its effect may continue to drive a shift in testing volumes in the coming years. “The benefit of competition and a broadening market is greater BRCA awareness,” says Murphy. “It is not a zero-sum game and [every competitor] is not taking away from Myriad. The market has grown.” Continued growth will emerge in part from changes to clinical guidelines, which are both expanding which patient population the test is relevant for as well as for additional BRCA components. But the larger growth opportunity is expected through greater penetration of the asymptomatic market. “The oncology market—those diagnosed with breast or ovarian cancer—is relatively penetrated. The real growth will be in asymptomatic people—those with a family history,” explains Murphy. “It is underpenetrated. Less than 10 percent of them get the test, so there is a lot of growth there.” Also, there are drugs that are poly ADP-ribose polymerase inhibitors that will only work with BRCA mutations, so if these drugs are approved in 2014 or 2015 it will further expand the market for BRCA testing in all patients as a companion diagnostic. Despite optimism over the future growth of BRCA-related testing, the fierce competition among the new market entrants has raised some concerns among genetic counselors. In response to what they call “aggressive and manipulative tactics” in which genetic counseling centers have been pressured by clinicians with financial ties to specific laboratories and reports of laboratories threatening to “siphon-off referring clinicians if their laboratory isn’t used,” counselors from the Yale Cancer Center Genetic Counseling Program posted a “Genetic Testing Lab Position Statement.” They call on providers to utilize “patient-centric criteria, including open access to data, to make decisions about genetic testing laboratories.” While acknowledging some caveats in which laboratory choices “must sometimes be based on insurance plan regulations, test availability, or the lab’s previous experience with a rare familial mutation,” the counselors say that decisions on laboratory selection should be based on quality, turnaround time, cost, and open access to data generated from testing. “Whenever possible we will choose laboratories that have pledged to make all of their past, present, and future gene data publicly available in order to allow this important information to be freely accessible to all clinicians and researchers, to further the advancement of medical knowledge and to best serve patient care,” write the counselors in a supporting blogpost. “The benefits of more market entrants is that it raises the profile to make the test more routine, and of course there has been a cost reduction,” says Evans. “But it has also made testing more open with data-sharing, which is a positive trend.” Takeaway: BRCA testing volumes are likely to grow in the short term as more asymptomatic patients with a family history of breast and ovarian cancer seek testing due to increased public awareness. A growing number of market entrants will service this volume with a decided shift toward multigene panels for hereditary cancers.