Natera Announces Publication of Analytical Validation Study Demonstrating Superior Precision of Its Kidney Transplant Rejection Assay
Core Technology Delivers Superior Analytical Performance, Underpins Outstanding Clinical Performance
SAN CARLOS, Calif., Feb. 22, 2019 /PRNewswire/ --Natera, Inc. (NASDAQ: NTRA), a leader in cell-free DNA, 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'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.3Natera 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,4Natera 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.
About Natera's dd-cfDNA Organ Transplant Assay Natera's organ transplant rejection assay is designed to detect active allograft rejection in patients who have undergone renal (kidney) transplantation. The assay works by measuring the fraction of donor-derived cell-free DNA (dd-cfDNA) in the recipient's blood, which can spike relative to background recipient cfDNA when the transplanted organ is injured due to immune rejection. The assay leverages Natera's core single-nucleotide polymorphism (SNP)-based massively multiplexed PCR (mmPCR) technology to more accurately measure dd-cfDNA levels without the need for donor genotyping. It has been clinically and analytically validated for test performance independent of donor type, rejection type, and clinical presentation.
About Natera Natera is a global leader in cell-free DNA testing. The mission of the company is to change the management of disease worldwide. Natera operates an ISO 13485-certified and CAP-accredited laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, Calif. It offers a host of proprietary genetic testing services to inform physicians who care for pregnant women, researchers in cancer including bio pharmaceutical companies, and genetic laboratories through its cloud-based software platform. For more information, visitnatera.com. Follow Natera onLinkedIn and Twitter.
Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera's plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to our efforts to develop and commercialize new product offerings, our ability to successfully increase demand for and grow revenues for our product offerings, whether the results of clinical studies will support the use of our product offerings, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera's recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available atwww.natera.com/investors and www.sec.gov.
The test was developed by Natera, Inc. a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although FDA does not currently clear or approve laboratory-developed tests in the U.S., certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.
Contacts Investor Relations: Mike Brophy, CFO, Natera, Inc., 650-249-9090 Media: Andrea Sampson, Sullivan & Sampson, 714-374-6174, email@example.com
Altuğ Y, Liang N, Ram R, et al. Analytical validation of a single-nucleotide polymorphism-based donor-derived cell-free DNA assay for detecting rejection in kidney transplant patients. Transplantation, 2019
Grskovic M, Hiller DJ, Eubank LA, et al. Validation of a clinical-grade assay to measure donor-derived cell-free DNA in solid organ transplant recipients. J Mol Diagn. 2016;18(6):890-902.
Hart A, Smith JM, Skeans MA, et al. 2014 Annual report of the U.S. organ procurement and transplantation network and the scientific registry of transplant recipients: kidney. Am J Transplant. 2016;16(Suppl 2):11-46.
Sigdel TK, Archila FA, Constantin T, et al. Optimizing detection of kidney transplant injury by assessment of donor-derived cell-free DNA via massively multiplex PCR. J Clin Med. 2019;8(1):19.
Bloom RD, Bromberg JS, Poggio ED, et al. Cell-free DNA and active rejection in kidney allografts. J Am Soc Nephrol. 2017;28(7):2221-2232. doi: 10.1681/ASN.2016091034.
Wehmeier C, Amico P, Minkowski, PH, et al. Acute rejection phenotypes in the current era of immunosuppression: a single-center analysis. Transplantation Direct. 2017;3(3):e136. doi: 10.1097/TXD.0000000000000650.
Choi BS, Shin MJ, Shin SJ, et al. Clinical significance of an early protocol biopsy in living-donor renal transplantation: Ten-year experience at a single center. Am J Transplant. 2006;5:1354-1360.