Natera, Inc. today announced analytical validation study results to be published online in the journal Transplantation demonstrating the superior performance of its donor-derived cell-free DNA (dd-cfDNA) test for detecting active rejection in kidney transplant recipients.1 The study showed superior assay precision with coefficient of variation up to five times better than previously published studies.1,2 Natera (NASDAQ: NTRA), is a leader in cell-free DNA.
Natera’s analytical validation was based on the analysis of 1,064 replicate samples from both related and non-related donor-recipient pairs. Conducted according to rigorous guidelines from the Clinical & Laboratory Standards Institute, the validation study measured key properties of the assay, including lower limit of detection, linearity, and precision. The assay’s precision was particularly strong, showing a coefficient of variation up to five times better than that of a competitive dd-cfDNA assay (1.85% vs. 9.2% within run; 1.99% vs. 4.5% across runs) in repeatability and reproducibility studies.1,2
Previously published analytical studies using other dd-cfDNA assays did not include related donor-recipient cases (such as parents or siblings), which is notable given the technical challenge of differentiating DNA patterns from close relatives. It has been estimated that 52 percent of live kidney donations originate from biologically related donors.3 Natera has leveraged its deep experience using single-nucleotide polymorphism (SNP)-based methods to analyze fetal DNA in maternal blood to achieve high accuracy in these cases.
“We believe the excellent analytical performance can be attributed to the test’s underlying core technology, based on Natera’s unique SNP-based mmPCR method, which has been a key differentiator in the analysis of cell-free DNA in the prenatal setting, in oncology, and now in organ transplantation,” said Allison Ryan, Ph.D., Natera’s Vice-President of Data Science. “We achieved high precision by targeting more than 13,000 SNPs, selected to be informative regardless of ethnicity, optimizing the DNA extraction and library preparation to maximize performance, and by developing a unique bioinformatics method that is highly accurate, even in more challenging related donor-recipient cases.”
The excellent analytical performance of Natera’s dd-cfDNA assay underpins its superior clinical performance in detecting active allograft rejection (AR). In its recently published clinical validation study,4 Natera reported higher sensitivity (89% vs. 59%) and higher area under the curve (0.87 vs. 0.74) than the competing dd-cfDNA assay.4.5 In that study, Natera also outperformed the competing assay in detecting T-cell mediated rejection (TCMR), which represents approximately one-third of all AR diagnoses.6 In addition, it was the first assay to report high accuracy in detecting subclinical rejection, which occurs in 20-25 percent of patients in the first two years post-transplant7 and is considered a major driver of graft failure.
“The growing body of evidence from our analytical and clinical validation studies supports our belief that Natera’s non-invasive test will be a valuable tool for the management of kidney transplant recipients,” said Paul Billings, M.D., Ph.D., Natera’s Chief Medical Officer and Senior Vice President of Medical Affairs. “Our ultimate goal is to help physicians detect rejection earlier so that patients’ immunosuppression levels can be optimized before irreversible organ damage occurs.”
There are more than 190,000 people living with a kidney transplant in the U.S.8 and roughly 20,000 new kidney transplant surgeries are performed each year.9 It is estimated that 20-30 percent of organ transplants fail within five years and approximately 50 percent fail within 10 years.10,11 The current tools for diagnosing organ transplant rejection are either invasive (biopsies) or inaccurate (serum creatinine), creating a strong unmet need for better diagnostic tools to improve patient management and outcomes.
The study, titled Analytical Validation of a Single-Nucleotide Polymorphism-Based Donor-Derived Cell-Free DNA Assay for Detecting Rejection in Kidney Transplant Patients, will be available here.