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12:39 pm
Fri February 17, 2012

C-HIT: Is Myriad's Patent on Breast Cancer Genes Valid?

As Myriad Genetic Laboratories nears its one millionth predictive genetic test for hereditary breast and ovarian cancer, the cost of the test has more than doubled, and the company’s 15-year patent monopoly is being challenged by critics who contend it is stymieing other potentially life-saving screening.

In addition, more than 140 researchers, doctors and clinicians affiliated with the Yale Cancer Center and from institutions all over the country, have written an open letter to Myriad raising concerns that the so-called BRAC Analysis test does not detect “a significant proportion of BRCA1 and BRCA 2 mutations” and therefore is not truly “comprehensive.”

They say an additional analysis, known as BART (BRAC Analysis Rearrangement Test), is necessary, but not always accessible—especially for Hispanics, who show in Myriad testing to be at high risk for the large-rearrangement mutations. The BART test, also licensed by Myriad, costs $700 and is not widely approved for insurance coverage.

“As you know, most insurance companies do not cover the extra BART Analysis and most patients do not have this important testing,” the Yale group wrote. “This means we are missing BRCA mutations in many patients, which is costing lives.” The Yale group said Myriad never responded to the letter.

The controversy over Myriad’s testing monopoly is up for a hearing before the U.S. Supreme Court. The American Civil Liberties Union and the Public Patent Foundation are leading 20 plaintiffs, representing more than 150,000 interested parties challenging Myriad’s right to patent genes and set prices that “lock out” some women from being able to afford the test.

The suit, which claims that the patents unfairly limit both scientific research and patient options for genetic testing, raises broad legal and ethical questions under the First Amendment about whether genes are “products of nature” or commercial commodities.

“For a gene with such widespread use to be held by a single company restricts both clinical and research testing, to say nothing of the cost,’’ said Ellen Matloff of New Haven, one of the plaintiffs in the case. A research scientist in genetics at the Yale School of Medicine and director of Cancer Genetic Counseling at the Yale Cancer Center, Matloff said she joined the lawsuit as an individual not only to challenge the company’s monopoly on genes, but because of concerns about “the unprecedented way in which Myriad enforced these patents on other labs, and its direct-to-consumer marketing practices that widely advertise a genetic test that is not necessary for most of the population.”

The Utah-based Myriad has argued, “Since a landmark US Supreme Court decision in 1980 relating to gene patenting, the US Patent and Trademark Office has granted tens of thousands of genetic and genetic related patents which cover a large number of life-saving pharmaceutical and diagnostic products…Myriad strongly believes that its patents are valid and enforceable and will be upheld by the courts.”

BRCA1 and BRCA2 are human genes that belong to a class of genes known as tumor suppressors. A woman’s risk of developing breast and/or ovarian cancer is greatly increased if she inherits a deleterious BRCA1 or BRCA2 mutation. Women who test positive for mutations are counseled about a number of options, including increased surveillance via MRIs, prophylactic surgeries such as mastectomies and oophorectomies, and chemoprevention such as Tamoxifen.

When the genetic mutations were first discovered, several labs, including the DNA diagnostics lab at Yale, offered the BRCA 1/2 mutation testing for $1,600. Soon after Myriad received its patent in 1996 for a comprehensive BRAC Analysis, the cost jumped to $2,400. And, while the cost of other comprehensive genetic testing has dropped over the ensuing years as technology and computer capability have advanced, the cost of the BRAC Analysis has risen to $3,340.

“There are many examples of lower-cost testing,” Matloff said. “For example, whole exome sequencing, which reads (thousands) of genes tied to proteins within a genome, is now available for less than Myriad’s charge for the comprehensive BRAC Analysis on only two genes.”

A United Kingdom firm, NewGene, has developed next-generation, sequencing-based BRCA 1/2 testing that costs only $950. Myriad has so far aggressively refused to license its patent and allow other labs to develop and market tests for the BRCA 1/2 mutations in the U.S. Myriad is preparing to enter the European market, company officials have indicated.

A gene patent holder has the right to prevent others from studying or testing a gene, according to the ACLU. Critics claim this prohibition is hampering progress on breast cancer. “As a result, scientific research and genetic testing has been delayed, limited or even shut down due to concerns about gene patents,” the lawsuit says.

In March 2010, a New York federal court rattled the biotech industry when it ruled that the patents on the BRCA1 and BRCA 2 genes were invalid. Myriad appealed the decision, and in a 2-1 decision in July, the U.S. Court of Appeals for the Federal Circuit reversed the ruling, finding that companies can obtain patents on the genes but cannot patent methods to compare those gene sequences. The court based its decision on the finding that isolated DNA is “markedly different” from DNA occurring in nature.

As the lawsuit has worked its way through the courts, the debate has expanded beyond Myriad, onto the notion of whether human genes can be subject to patents at all.

The Price Of Detection
Most private insurers, as well as Medicaid and Medicare, provide coverage for the comprehensive BRAC Analysis and some less costly single-site tests.

But co-pays and deductibles vary – as do eligibility requirements—which lawsuit plaintiffs say still “lock out’’ many at-risk insured women from being able to afford the procedure.

Connecticut has the second- highest incidence of female breast cancer in the nation – with 2,920 new breast cancer cases diagnosed in 2008, according to the Community Profile of Breast Health in Connecticut released last year by Susan G. Komen for the Cure CT. Using the estimates that five to 10 percent of breast cancers are caused by these mutations, as many as 290 of the new cases were in people likely to have the BRCA 1/2 mutation.

Connecticut ranks 35th in the nation for breast cancer mortality and 490 women in the state died from the disease in 2008.

Rebecca Chambers, director of investor relations and corporate communications for Myriad, said more than 90 percent of the BRAC Analysis tests ordered by health care providers are covered by insurance. She also said that the company provides limited free genetic testing, as well as “zero-interest, no qualifying” financing and free phone genetic counseling services.

“There are more than 2,600 insurance payers, comprised of more than 80,000 insurance plans covering over 130 million lives, which reimburse for the BRAC Analysis test,” Chambers said. “Our average reimbursement is $3,000. . .

“We understand that there are patients in our country who do not have insurance and need help,” Chambers said. Since 1996, she said, Myriad has provided free testing to low-income, uninsured patients. In the last three years, Chambers said, more than 4,700 patients have received free BRCA testing.

In their letter to Myriad, the Yale clinicians cited the company’s own data on the high risk Hispanic population, saying it could result in financial hardships.

“This Hispanic population is one of the most rapidly growing ethnic groups in the United States and is disproportionately uninsured, underinsured, and at or below poverty levels,” they wrote. “Therefore, this population is less likely to be able to access and afford the necessary, expensive, additional BART testing.”

The Yale group asked that the BART analysis be included in Myriad’s standard BRAC Analysis test for all patients. Among its arguments is that Myriad could afford to merge the tests. In January, Myriad reported its second quarter in a row of 20 percent or greater year-over-year revenue growth.

In Connecticut, the Hispanic Health Council counsels women to get breast exams, through its Early Breast Health Program. Women served by the program, who are uninsured or underinsured, are referred for free services at area hospitals and clinics. Program coordinator Awilda Maldonado said she had “never heard of anyone” in the program receiving either the BRAC 1/2 or the BART test.

“I can tell you right off the bat, nobody from the clinics [that serve the program] has offered any genetic tests,” Maldonado said. “It’s hard enough to get them an appointment for a clinical breast exam, never mind a BRAC test. Sometimes there is a waiting list just for an exam.”

Elizabeth Krause, senior program officer at the Connecticut Health Foundation, which works to combat racial and ethnic health disparities, said Latinos, as well as other minorities, face multiple barriers to accessing preventative breast health care, including a lack of both health insurance and “health literacy” in understanding genetic testing options.

“A Latino woman would first have to understand her family history and then contact her insurance company to see if the test is covered, and then weigh the cost-benefit” of genetic testing, Krause said. “There are all the barriers in the world” to accessing BART or BRAC testing.

Chambers said Myriad has provided free BART testing over five years, valued at over $20 million, to patients with a more severe risk of carrying a BRCA1 or BRCA2 mutation, and has generated data required by medical professional societies for establishing guidelines for the tests. She noted, however, that most insurance carriers currently do not provide reimbursement for BART, “as it is not included as a recommended test under guidelines like those from the National Comprehensive Cancer Network. Once the test is incorporated into guidelines, “she added, ” we will work with payers to obtain reimbursement.”

Gauging The Risks
For women who have had breast or ovarian cancer before the age of 50, and/or has an immediate family member who has had one of these cancers, the genetic test could be a lifesaver.

Research shows that 5 to 10 percent of all breast cancers are in people who have inherited BRCA mutations. The mutations can signal a 60 to 85 percent lifetime risk for more than one primary breast cancer, and a 15 to 50 percent lifetime risk for ovarian cancer. The risk statistics for the general population are 12.2 percent for breast cancer, and 1.4 percent for ovarian cancer.

The testing also detects risk in men. If a man’s sister or mother has the BRCA 1 or BRAC 2 mutation, he has a 50 percent chance of also having it. Men carrying the mutation have a 6 to 7 percent chance of having male breast cancer, compared to less than 1 percent in the general population.

Men who carry the gene also have an increased risk of prostate cancer. And, like women, men have a 50 percent chance of passing the mutation onto their offspring.

Access to the test for those who fall into risk categories is critical, cancer experts say. In Connecticut, about 135,000 women between the ages of 19 and 64 do not have health insurance, according to Kaiser’s State Health Facts, based on U.S. Census data. The U.S Preventive Services Task Force estimates that 2 percent of all women – or about 2,700 of the uninsured women in Connecticut—are likely candidates for the test.

State Medicaid programs cover the BRAC genetic testing if a medical professional orders that the test be done, regardless of whether the person has had cancer, according to David Dearborn, spokesman for the state Department of Social Services (DSS).
Under Medicare’s new guidelines, BRCA genetic testing is covered for certain groups of people who have already been diagnosed with cancer.

Most patients now pay additional fees to health care professionals for recommended pre- and post-test counseling and the test blood drawing. However, guidelines in the federal Affordable Health Care Act provide that on or after August 1, 2012, “BRCA counseling about genetic testing for women at higher risk… must be covered with no cost-sharing.”

Matloff believes that while the clock is ticking, lives are at stake.

“We’ve come to a fork in the road” on genetic testing, she said. “This particular lawsuit affects every human being on the planet—rich, poor, young, old, male, female, black, white, in the U.S. or elsewhere in the world. It holds great potential for the future of science, personalized medicine and our entire health care delivery system.” 

For a list of some cancer centers and organizations click here.

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