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CareDx HeartCare Tool More Effective Than Cell-Free DNA Testing Alone in Clinical Study

NEW YORK – CareDx's HeartCare product, which combines AlloSure Heart donor-derived cell-free DNA (dd-cfDNA) and AlloMap Heart gene-expression profiling (GEP), identified acute cellular rejection (ACR) better than dd-cfDNA testing alone and led to fewer biopsies among transplant patients.

The results, which analysts say have the potential to drive adoption and payor coverage, were published Wednesday in the Journal of Heart and Lung Transplantation.

The prospective, multicenter Surveillance HeartCare Outcomes Registry (SHORE) study evaluated 2,077 heart transplant recipients. Participants were tested via HeartCare and categorized as either AlloMap negative and AlloSure negative ("dual negative"), AlloMap positive and AlloSure negative, AlloMap positive and AlloSure negative, or AlloMap positive and AlloSure positive ("dual positive").

Dual-positive patients showed the highest incidence of acute cellular rejection, at 9.2 percent, whereas dual-negative patients had the lowest incidence, at 1.5 percent. Follow-up endomyocardial biopsies took place in 8.8 percent of dual-negative cases and in 35.4 of dual-positive cases.

While the sensitivity of dual-positive testing was approximately 32 percent, compared to 59 precent for gene expression profiling(GEP) alone and nearly 45 percent for dd-cfDNA alone, dual-positive testing specificity outperformed the others, at approximately 92 percent, compared to nearly 57 percent in the case of GEP alone and approximately 85 percent for dd-cfDNA alone.

The study investigators wrote that the specificity of both individual GEP and dd-cfDNA tests can be limiting in the context of ACR surveillance, when the pre-test probability of detecting ACR on any given biopsy is low, but that since they measure complementary pathophysiology, it makes sense for dual testing to improve results.

Throughout the study, physicians ordered the fewest number of follow-up biopsies for dual-negative results, while dual-positive results led to the highest number of biopsies, with single test positive results falling in between.

The study investigators said that this indicated that HeartCare testing results influenced physician behavior, with cardiologists performing 10 percent fewer biopsies in the first year post-transplant and 40 percent fewer in the second year post-transplant. Comparatively, follow-up biopsy rates for dual positives increased over the same time period.

Despite these trends, the investigators wrote that the overall rates of follow-up biopsies in dual-positive cases remained "surprisingly low," at approximately 35 percent, while those for dual-negative results remained "surprisingly high," at almost 9 percent. They attributed this finding to several factors, including the exclusion of molecular tests and biopsies performed on the same day, thereby eliminating early post-transplant tests, which are more likely to associate with rejection. They also noted that some dual-positive results may have been just over threshold levels, triggering an earlier follow-up test, rather than a biopsy; that dual-positive results that had been previously positive and accompanied by a biopsy may not have triggered a follow-on biopsy; and that there may have been limited knowledge of the implications of a dual-positive result early in the study.

Finally, patients managed with HeartCare maintained positive clinical outcomes despite fewer follow-up biopsies, with 95 percent of patients surviving and 97 percent showing normal allograft function at two years post-transplantation.

"This large, prospective, multicenter study demonstrates that HeartCare significantly improves clinicians' ability to assess acute cellular rejection risk, and its use is associated with lower biopsy rates and excellent clinical outcomes two years post-transplant," John Hanna, president and CEO of CareDx, said in a statement.

In an investor note, Bill Bonello of investment bank Craig-Hallum wrote that the study's results "should drive increased adoption and improved payor coverage."

Bonello noted that Medicare currently covers HeartCare for monthly surveillance testing in months two through 12 post-transplant, at a rate of $5,993 per test, and that Medicare provides no coverage beyond the first year.

Earlier this month, Craig-Hallum upgraded CareDx to a Buy rating.

Shares of CareDx were up approximately 3 percent in morning trading on the Nasdaq, at $15.15 per share.