Natera, Inc. (NASDAQ:NTRA), a global leader in cell-free DNA (cfDNA) testing, today announced the publication of a manuscript in a leading journal in the organ transplant space, Transplantation, validating the performance of a novel two-threshold algorithm for its Prospera™ test for the assessment of transplant rejection. Prospera incorporates the donor fraction and the estimated amount of donor-derived cfDNA (dd-cfDNA) when assessing active rejection. In the study, Natera’s new method demonstrated significantly improved performance compared to rejection assessment using donor fraction-alone.
The “Trifecta” study, led by principal investigator Phil Halloran, M.D., Ph.D., director of the Alberta Transplant Applied Genomics Centre, is currently enrolling at 25 sites globally. The first 367 samples from adult kidney transplant recipients meeting enrollment criteria were analyzed and included in the manuscript. These samples represent the largest prospective, fully biopsy-matched cohort with dd-cfDNA analysis for kidney transplant recipients conducted to date. Assessment of active rejection by the Prospera test was evaluated against RNA-based molecular pathology (Molecular Microscope® Diagnostic System, “MMDX”) and histological (Banff Classification of Allograft Pathology, 2019) assessment of the biopsy. The cohort in the Trifecta study features a total of 125 samples with biopsy-proven active rejections by MMDX and 142 samples with biopsy-proven rejection by BANFF criteria used to benchmark dd-cfDNA calls, exceeding both the 271 samples and the 1132 samples from biopsy-proven active rejections in previous dd-cfDNA testing studies.
The Prospera assay exceled at discriminating between active rejection and non-rejection, with AUCs of 0.88 assessed with MMDX, 0.82 assessed using the BANFF criteria, and an AUC of 0.91 compared to quiescence. The excellent performance further highlighted the value of the Prospera two-threshold algorithm, as the combination of dd-cfDNA fraction and estimated amount of dd-cfDNA outperformed either variable alone. The two-threshold algorithm detected six additional cases of rejection compared to using donor fraction-alone.
“This study shows that dd-cfDNA test performance, using the two-threshold approach, is substantially improved, and is highly correlated to other molecular methods such as MMDx,” said Dr. Halloran. “This is a key piece of evidence supporting the routine utilization of molecular methods to complement traditional biopsies for diagnosing rejection.”
“Our legacy of expertise in cfDNA analysis has enabled us to maximize the knowledge we derive from our tests, providing transplant recipients and their physicians with clinically actionable information from a single test,” said Sangeeta Bhorade, M.D., chief medical officer for organ health at Natera. “The excellent AUC of the Prospera test in this study establishes the importance of leveraging the combination of dd-cfDNA fraction and quantification vs donor-fraction alone.”