XDx presented data last week that provided further confirmation that its AlloMap molecular diagnostic test can accurately assess which patients are at low risk for heart transplant rejection and therefore can avoid invasive biopsy procedures.
The data was from the Cardiac Allograft Rejection Gene Expression Observational II study, which involved more than 700 heart transplant patients, including a European cohort. XDx is hoping that the results will drive adoption of AlloMap in Europe, where the test is CE-marked.
"It is critical to have data from patients in Europe in order for us to have confidence that AlloMap's performance is reliable for use with our patients," Maria Crespo-Leiro of Universitario A Coruna in Spain and the first author of the study, said in a statement.
Researchers from XDx and several European universities presented data from CARGO II at the International Society for Heart and Lung Transplantation's annual meeting last week. Patients were recruited from 17 sites, 13 of which were in Europe.
In the study, researchers analyzed blood samples from patients who had confirmed moderate to severe rejection based on endomyocardial biopsies to discern whether AlloMap scores could differentiate between patients at high risk and low risk of rejection.
"The mean [AlloMap] test scores for samples associated with" patients who experienced moderate to severe rejection "were significantly higher than test scores from samples from patients with no rejection seen on histology," the study authors concluded.
In CARGO II, researchers also found that the AlloMap test had a negative predictive value of 98.4 percent for patients between two to six months after getting a heart transplant, meaning that when the test yields a low score that patient will likely not experience rejection. However, the test only had a 4 percent positive predictive value, which means that when AlloMap yields a high rejection score for patients, it doesn't necessarily signal that they will experience a rejection.
AlloMap is a blood test that measures the expression of 20 genes and yields a score of between zero and 40. The lower the score, the lower the risk of transplant rejection. In CARGO II, positive and negative predictive values were analyzed with a test value cutoff of 34, below which patients were considered at low risk of rejection.
XDx is hoping that data from the study will help drive adoption in Europe. A company spokesperson told PGx Reporter that several German hospitals began offering AlloMap in March. In the second quarter of this year, the company hopes to launch AlloMap in additional German transplant centers, as well as in Switzerland and Austria, marking the first phase of a broader European launch for the test.
"The primary European markets are predominantly single payor, and indeed XDx is working on a country-by-country basis," the company spokesperson said.
"XDx is developing a health economic dossier based on AlloMap’s clinical utility and cost effectiveness that will be included in pricing and reimbursement applications to the various European payors," the spokesperson said.
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. Given that heart transplant patients often undergo 12 biopsies in the first year following transplantation, studies like CARGO II that suggest that AlloMap could potentially reduce the number of biopsies a transplant patient receives could be a compelling cost-effectiveness argument for payors.
By conducting CARGO II, XDx primarily aimed to confirm data from the CARGO study, the pivotal trial the US Food and Drug Administration used to grant US marketing approval of AlloMap in 2008.
In the US, the test is indicated as a diagnostic to help doctors identify patients who have a low probability of rejecting their heart transplants. According to the FDA-cleared label, patients who are younger than 15 years or have had their new hearts for less than two months should not be monitored for rejection with AlloMap.
In CARGO, for patients who were between two and six months post-transplant, AlloMap had a negative predictive value of 98.2 percent, while for those who were more than six months post-transplant, the test had a negative predictive value of 98.9 percent.
"The CARGO II results independently confirm and extend the AlloMap test performance characteristics previously established in the US-based CARGO study," the study authors reported in their ISHLT presentation.
The XDx spokesperson noted that CARGO II doesn't prove that the molecular diagnostic is superior to cardiac biopsies, since histology assessments were the reference standard in the trial.
In the IMAGE trial, published in the New England Journal of Medicine in 2010, researchers randomized 602 patients for monitoring of heart transplant rejection either with the use of AlloMap or with the use of routine endomyocardial biopsies, and found that AlloMap was non-inferior to cardiac biopsies in identifying which patients will experience a rejection event. However, the authors of this study concluded that the genomic test was a reasonable alternative to biopsies only for transplant patients who had their new hearts for at least six months (PGx Reporter 4/28/2010).
According to senior CARGO II author Johan Vanhaecke of University Hospital of Leuven in Belgium, the researchers are planning to further study this cohort of patients to assess whether serial AlloMap testing can predict rejection events long term and be used to personalize treatment with immunosuppressive regimens.