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With Updated Messaging Around AlloMap, XDx Boasts Record Test Volume in 2013

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Originally published Jan. 7.

XDx's decision to alter its messaging to doctors about when and how its multi-gene AlloMap cardiac rejection test is best used following a patient's heart transplant has apparently served the molecular diagnostics firm well.

According to CEO Peter Maag, in 2013 XDx experienced a 20 percent jump in the number of AlloMap tests performed, compared to a 2 percent test volume growth in 2012. "We had an alignment of resources that allowed us to be EBITDA [Earnings Before Interest, Tax, Depreciation And Amortization] positive over the last quarter, which for a small biotech company like XDx … is a substantial achievement," said Maag, who joined XDx in late 2012 with a mandate from the firm's board to spur AlloMap's growth.

The company reported 10,000 patient results over the past year. While Maag couldn't provide too many financial details for the privately held firm, he said the company anticipates netting $22 million in revenues in 2013.

“We've set goals and talked about being profitable for many years and not reached it," Maag told PGx Reporter. He attributed the spike in AlloMap use to XDx's conscious effort to reposition AlloMap as a risk-stratification tool for certain heart transplant patients instead of a replacement for cardiac biopsies.

"We used to market AlloMap head to head against biopsies in the US, but what we learned from clinicians is that they're using it much more as a surveillance monitoring tool, and we generated clinical data that allows us to talk about patient stratification following multiple AlloMap tests," Maag said. "So, it's not a one-time test that tells you if the person is rejecting [the transplant] or not. It's more in the context of how do you risk stratify a patient based on multiple test scores."

FDA-cleared AlloMap is a blood-based test that gauges the expression of 20 genes and yields a score of between zero and 40. Brisbane, Calif.-based XDx has been marketing AlloMap in the US since 2005 and performs the test through its CLIA lab.

To date, the company has reported to patients more than 50,000 test results. Doctors can use the test scores, in addition to standard clinical measures, to determine whether transplant patients with stable allograft function are at low risk of rejecting their new hearts. The lower the score a patient has, the lower his or her risk of organ rejection.

"Reinvigoration is possible in the genomics field. It takes a lot of time," Maag said, discussing XDx's success in the previous year growing the AlloMap franchise. "The story used to be all about growth, growth, growth, and worry about profitability later. What we have demonstrated is that with a single product one can be profitable as well."

Before Maag joined XDx, the company was having trouble getting transplant surgeons to adopt AlloMap in their armamentarium. Even though endomyocardial biopsies – the standard method of tracking transplant patient's risk for rejection – are invasive and can lead to costly complications, XDx couldn't get many doctors to use the blood-based molecular test.

XDx officials have previously attributed this reluctance on the part of transplant surgeons to adopt AlloMap as a financial issue. Physicians can hope to see between $200 and $300 per endomyocardial biopsy performed, and this can add up since some transplant recipients must undergo as many as a dozen biopsies in the first year after receiving their new heart. However, doctors aren't reimbursed for sending patients' blood samples to a lab for genetic analysis.

"I think a lot of transplant programs are reluctant to use this test because they don't get the revenue for doing heart biopsies," Andrew Kao, medical director of cardiac transplant at the Mid-America Heart Institute in Kansas City, Mo., told PGx Reporter. "So, a lot of doctors will say they don't believe in this test because biopsies are standard."

At the Mid-America Heart Institute, doctors use AlloMap routinely on most patients they consider to be at low risk for rejection. The Institute has a protocol in place to begin testing low-risk patients on AlloMap starting at four months after their surgery and up to three years post-transplant. According to Kao, doctors at the institute have performed thousands of AlloMap tests.

While XDx has stopped promoting AlloMap as a biopsy replacement, doctors that have incorporated the molecular diagnostic into their portfolio of surveillance tools for heart transplant patients are using it in place of the more invasive procedure for low-risk patients. Kao noted that he repeats the AlloMap test every time the patient would have had a biopsy. "So, this is basically replacing biopsies for our patients," he said.

XDx has conducted multiple studies showing that the stability of AlloMap scores over time for a patient correlate with his or her outcomes post transplant. For example, in the CARGO II study involving patients with more than two AlloMap test scores, researchers found that study participants' scores increased and became stable during the first year after getting their new hearts. After the first year, high AlloMap scores and score instability was associated with future events that can lead to rejection or death.

In another study, called IMAGE, researchers reported that by tracking the stability of AlloMap scores for patients who had been tested at least twice, they could predict negative outcomes, such as death or allograft dysfunction, more accurately. Moreover, longitudinal data from multiple AlloMap tests may be more prognostic than a single AlloMap score at a given point in time, researchers found.

Kao and his colleagues at the Mid-America Heart Institute are working with XDx to develop predictive models for gauging severe rejection in transplant patients using multiple AlloMap scores.

According to XDx's Maag, the company is conducting AlloMap testing on approximately 1,500 new patients each year. He estimated that, on average, patients get tested on AlloMap four times after transplantation. Given the frequency with which doctors need to perform cardiac biopsies for some patients though, "that could easily be up to 10 [AlloMap] test results," he noted. "So, there is still a substantial potential [patient population] for us to capture."

While the bump in 2013 test volume suggests that XDx has successfully swayed some physicians to adopt AlloMap, not all transplant centers are using it in a standardized fashion. For example, cardiologist David Lanfear at Henry Ford Hospital has ordered AlloMap tests for some of his patients but hasn't incorporated testing routinely into practice. Lanfear and his colleagues at Henry Ford Hospital typically test patients on AlloMap a year after they've received their transplants, particularly if patients have been stable during the first six months after surgery when they are at the highest risk of a serious adverse event. "We choose not to do it in those patients if they've had rejection recently," Lanfear said.

Data from CARGO II showed that AlloMap had a negative predictive value of 98.4 percent for patients between two to six months after getting a heart transplant, and a 4 percent positive predictive value. As such, a low AlloMap score indicates a patient is unlikely to experience rejection, but a high rejection score doesn't necessarily signal that a patient will experience a rejection.

In Lanfear's view the real barrier to adoption for AlloMap is that despite the drawbacks of cardiac biopsies, transplant surgeons are comfortable with this procedure. "If there is a slowness of uptake it's because it's hard for people in the transplant business to change how they do things," he acknowledged. "If things are going well with the way you've been doing things, you don't typically change it."

Molecular diagnostics, such as AlloMap, with very specific indications, are often perceived as having insufficient evidence when held up against industry gold standard data requirements. While the 700-patient CARGO and CARGO II studies were large, well-designed trials for the heart transplantation community, in terms of cardiac studies overall, these appear small, Lanfear said.

"You just generally don't have the level of evidence for anything we do in [the heart transplant area] comparison to other things in cardiology," he said. "In a lot of ways, you're left with anecdotal knowledge. So, adaptation to things like [AlloMap] is slow."

Other than marketing AlloMap as a risk-stratification tool for heart transplant patients, the company has also been persistent with the message that the molecular diagnostic is more cost effective than biopsies. AlloMap carries a list price of more than $3,000 in the US. In comparison, cardiac biopsies can range from between $4,000 and $10,000. XDx claims that AlloMap can identify the 80 percent of heart transplant patients who are at low risk of rejection. And if AlloMap can effectively reduce the need for biopsies in this group, it could amount to significant saving to the healthcare system.

Kao acknowledged that although by performing AlloMap payors can hope to save money by avoiding the higher costs and complications associated with biopsies, his institute is likely losing money by reducing the number of biopsies performed on heart transplant patients. "Despite that, our philosophy has been to do whatever is best for the patient, even if there is less revenue for us," he said.

Lanfear isn't sure that loss of reimbursement is that large a deterrent for AlloMap uptake within the cardiology community. While losing that revenue source might deter some individual doctors from adopting AlloMap, particularly those in private practice, Lanfear pointed out that reimbursement doesn't have much bearing on the income of salaried doctors at most transplant centers, such as those at Henry Ford Hospital. "It might hurt the institution in terms of the money coming in," Lanfear said, adding that the decision whether or not to use AlloMap is likely to be left up to the physician and not institutional policy. Not doing biopsies for transplant patients "doesn't hurt my salary at all," he added, attributing the adoption challenges for AlloMap mostly to "cultural issues."

Another barrier may be that patients' blood samples for AlloMap testing must be drawn at more than 100 XDx designated sites located across the US. "From a practical standpoint, what's been a pain is that the blood sample has to be drawn from a specific lab," Lanfear said. "So, you can't just send it from your site, and the patient has to go somewhere else."

Regardless of whether they are performing AlloMap testing routinely or sporadically for patients, neither Kao nor Lanfear reported much difficulty garnering insurance coverage for the tests they've done. "Over the last three years more and more insurers are willing to pay for the test," Kao said, noting there are still a "few hold outs."

According to XDx's Maag, payors in the US are covering 84 percent of all AlloMap tests performed in the country. "I think more … payors are getting the hang of the fact that this is important to transplant care," he said. "We're building the data and they buy into the concept. So, if you ask me it's time and good data that convinces these payors."

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