Natera, Inc. announced clinical validation study results published in the Journal of Clinical Medicine, demonstrating the highly accurate performance of its donor-derived cell-free DNA (dd-cfDNA) test for active allograft rejection in kidney transplant recipients, including higher sensitivity and nearly 18% higher area under the curve (AUC) than the competitive dd-cfDNA assay. The study also reports the first accurate detection of T-cell mediated rejection (TCMR) and subclinical rejection. This marks the successful completion of all 2018 commercialization milestones, and is in line with the company's plan to secure Medicare coverage and commercially launch its test in 2019. The blinded study, conducted in collaboration with the University of California, San Francisco (UCSF), leveraged Natera's massively-multiplexed PCR (mmPCR) technology to measure dd-cfDNA levels in plasma collected on the same day as a kidney biopsy from 193 unique kidney transplant recipients. The primary analysis focused on 217 plasma samples from 178 unique kidney transplant patients, including 38 cases of histologically-confirmed active rejection (AR), making it the published study of its kind, with approximately two times more patients and 40 percent more affected cases of AR than the next study. Another strength of the study is its broad ethnic diversity, which is important because kidney transplant assessment and biomarker performance are known to vary by ethnicity. In the study, Natera's assay detected AR with 89% sensitivity and 0.87 AUC. This test performance compared favorably to the current standard of care, eGFR (estimated glomerular filtration rate), which is a clinically accepted but inaccurate biomarker for AR. The study results also showed higher sensitivity (89% vs. 59%) and higher AUC (0.87 vs. 0.74) than the competitive dd-cfDNA assay. This superior data may be due to differences in the analytical performance and underlying technology behind the assays. The new study also had two novel, clinically significant findings: TCMR detection: Test performance was independent of rejection type, including antibody-mediated rejection (ABMR, 16 cases), T-cell mediated rejection (TCMR, 10 cases), and combinations of the two (ABMR/TCMR, 12 cases). By contrast, previous dd-cfDNA studies reported a poor ability to detect TCMR, which represents approximately one third of all AR diagnoses, and more than half of the AR cases in certain patient subgroups. Subclinical AR detection: Test performance was also independent of clinical presentation, demonstrating high accuracy in detecting both clinical and subclinical AR. The study was unique in that 13 of the 38 AR cases were diagnosed using protocol (or surveillance) biopsies, in contrast to the other 25 cases diagnosed using for-cause (or clinically-indicated) biopsies. The 13 cases are considered "subclinical AR," because the patients otherwise had stable renal function based on serum creatinine, showing no clinical signs of rejection. In the study, Natera's assay detected the subclinical AR cases with 92% sensitivity and 75% specificity. No other dd-cfDNA assay has been validated to detect subclinical AR, which occurs in 20-25% of patients in the first two years post-transplant, and which is considered a major driver of graft failure.