In the lofty confines of biochemistry laboratories and the rarefied world of peer-reviewed journals, scientists with big brains have used the map of the human genome to demonstrate that breast cancer is not a single disease, but rather many different diseases – each one bearing its very own genetic fingerprint.
This heady principle has revolutionized how oncologists view and treat breast cancer.
It has also triggered trench warfare in the oncological marketplace, where two young companies are engaged in heated battle for financial and intellectual advantage. While their laboratory scientists studiously apply genomic principles to produce test results that can determine the future course of a woman’s disease, their executives and chief medical officers are taking aim at one another, each company dismissing the other’s methods amid a blizzard of claims and counterclaims.
Agendia, a Dutch-born company whose executive offices are housed in the immaculate neighborhood of high-tech labs and auto dealerships that straddles Bake Parkway in south Irvine, is one of those companies. It sells a test that analyzes the behavior of 70 genes it says are the most closely associated with determining whether a breast tumor, if untreated, will ultimately colonize other parts of a woman’s body.
The results show early on whether a given breast-cancer patient runs a low or high risk of her disease spreading – an ultimately incurable event known as metastasis. Agendia’s test, known by the brand name Mammaprint, is increasingly used by oncologists, who say it is a valuable tool because it can help them decide whether a patient can safely forego chemotherapy even when other, more established clinical markers would argue for it.
But Mammaprint is largely overshadowed by a similar test, Oncotype DX, which belongs to Genomic Health Inc. of Redwood City.
The companies are duking it out for a share of a burgeoning new technology that is applicable to other cancers, including colon and lung, and could bring in billions of future health care dollars.
Both companies conduct the tests in their laboratories on tumor tissue that is taken during surgery or biopsy from recently diagnosed breast-cancer patients. They study the activity of a group of cancer-related genes in a given tumor and calculate scores that correspond with the likelihood of future metastasis. Genomic Health says its score can also predict how likely a patient is to benefit from chemo.
Marketplace war
Each company argues that its test can spare thousands of women the suffering and long-term ravages of chemo, while saving the health care system tens of billions of dollars that would otherwise be spent on treatments that offer little benefit to patients. Each one fiercely contests the validity of the other, battling it out for acceptance in oncologists’ offices.
“They’re very competitive. There’s a war going on in the marketplace,” says John Link, medical director of Breastlink in Orange and author of “The Breast Cancer Survival Manual.” Link says he has accepted money from both companies at different times for speaking or attending seminars.
Genomic Health, a publicly traded company, brought its test to market in 2004, one year after Mammaprint was first sold. But it has long since overtaken Agendia in market share and financial clout. Last year, the Northern California company reported net income of $8.25 million and revenue of $235.2 million, a marked improvement from the loss of $9.4 million on revenue of $149.6 million it had posted three years earlier.
Agendia, by contrast, is not yet profitable. It is not a publicly traded company and therefore is not obliged to report financial information. But Agendia’s chief executive, David Macdonald, said the company had revenue of $15 million in 2012, which it expects to double to $30 million this year. He said the company will be profitable in 2014, once it achieves revenues somewhere north of $30 million.
Agendia performs tests for U.S. patients – which are widely reimbursed by private insurers and Medicare – at its laboratory in Irvine. For European patients, the tests are conducted in Amsterdam, where the company originated as a spinoff of the Netherlands Cancer Institute. The company employs about 60 people in Irvine and 50 in Amsterdam, where it still conducts the lion’s share of its research and development.
Stealing market share
The company’s chief marketing executive, Douglas Bradley, says it is starting to take market share away from Genomic Health, in part because Mammaprint is prescribed for a wider range of breast cancer cases and because it can now be used on tumor tissue that is embedded in paraffin – a standard practice among pathologists in the U.S. that had marginalized the company’s fresh-tissue testing method.
Bradley estimates that Agendia has taken about 9 percent of former Genomic Health customers since it launched its paraffin-embedded test in January 2012. That number is difficult to verify, but it does appear that Genomic Health is feeling the heat.
In its most recent earnings call with investors and analysts, Genomic Health’s chief medical officer, Steven Shak, sought to portray Agendia’s Mammaprint as an inferior product. He pointed to a recent study showing that 45 percent of patients who were labeled high-risk by the Agendia test got a low-risk score when Oncotype DX was run on their tumor tissue.
“This discordance clearly emphasizes the clinical limitation of the 70-gene test,” Shak said, referring to Agendia not by name but by its specific genomic method. The Oncotype test analyzes just 16 genes compared with Agendia’s 70 – one of the many points of contention between the two companies.
Agendia’s chief financial officer, Glen Fredenberg, responds, “Certainly they are worried about us or they wouldn’t have spent five minutes on their last earnings call trashing us.”
Macdonald, the Agendia CEO, said that merely showing how the two tests diverge says nothing about which one is right. What counts are patient outcomes, he said, pointing to a study in which 97 percent of women who declined chemo after a “low-risk” Mammaprint score remained disease-free after five years, while a similarly large proportion of high-risk patients who got chemo were also free of metastasis.
That study, Agendia argues, suggests that the number of breast cancer patients getting chemo could be reduced by 20 percent based on the Mammaprint test.
Study criticized
Genomic Health, which makes similar claims about Oncotype DX, strongly contests the Agendia data. Shak dismissed the publication in which it appeared – the International Journal of Cancer – as “fifth-rate,” and he said the study was flawed because half the patients in it were not followed for the full five years.
Agendia’s chief medical officer, Neil Barth, flatly rejected Shak’s contention as “ridiculous.” The company’s chief clinical officer, Bastiaan van der Baan, says that “the vast majority” of patients in the study were followed for at least five years.
The companies also go toe-to-toe over the type of ratings scale used by each test to determine the risk of metastasis. Mammaprint rates patients as low-risk or high-risk, while Oncotype has an “intermediate” category.
Macdonald says Mammaprint’s cut-and-dried rating provides cancer doctors clear results to help inform their treatment decisions. Oncotype’s middle category, he says, “is a huge problem for doctors and their patients – and for payers, who are paying a whole lot of money for something that doesn’t give them an actionable result.” Shak bristles at the notion of high- and low-risk only, saying that Genomic Health’s approach is more in line with reality. “We are just being honest. There is a continuous biology; there aren’t just two groups,” he says. “The idea that patients are either high or low just strikes me as a marketing campaign. If you are close to the middle, do you think you just fall off the cliff?”
Listening to Genomic Health or Agendia, you could be excused for thinking that the other company was operating on the flimsiest of scientific principles. Given the stakes, perhaps that is not surprising.
The professionals who use the tests find value in the contributions made by both, though some have their preferences.
Lisa D. Curcio, a surgical breast oncologist in Aliso Viejo, said, “Recently I am using Mammaprint more,” along with a complementary test by the company, “because it is giving me more information I can use in my treatment decisions.” Norman Wolmark, an oncological surgeon who is chairman of the highly respected National Surgical Adjuvant Breast and Bowel Project, called Oncotype “the gold standard.” He added, “The breadth and depth of data available for Oncotype DX is by far and away greater than other tests that are out there.”
Link, the Orange-based oncologist, says that thanks to both Mammaprint and Oncotype, he is using significantly less chemo than he did eight years ago. These new tests have made a major difference in practice,” he says. “Both have been a huge boon.”
