Study represents the largest prospective, fully biopsy-matched cohort of dd-cfDNA for kidney transplant recipients
AUSTIN, Texas, Nov. 3, 2021 /PRNewswire/ — Natera, Inc. (NASDAQ: NTRA), a leader in personalized genetic testing, today announced the initial results1 from the global, multi-site, prospective Trifecta study led by Phil Halloran, M.D., Ph.D., director, Alberta Transplant Applied Genomics Centre.
The Trifecta study was designed to assess the performance of donor-derived cell-free DNA (dd-cfDNA) and to evaluate the relationship between dd-cfDNA, donor-specific antibodies and molecular pathology. The initial analysis includes more than 300 sequential biopsy-matched samples, drawn between 2019 – 2021, with over 100 biopsy-confirmed rejections from more than 20 U.S. and international sites. This represents the largest prospective, fully biopsy-matched cohort evaluating dd-cfDNA for kidney transplant recipients and includes roughly twice as many biopsy-matched rejections than any previously published prospective study.
In the validation cohort, when differentiating rejection from non-rejection, Prospera with Quantification delivered an AUC of 0.81 using the 2019 BANFF criteria, and 0.89 using molecular pathology, as the standards for rejection. Recent studies have shown that molecular pathology may be more accurate in diagnosing the rejection status in kidney transplant biopsies and therefore may be a better way to measure true cfDNA test performance.
The Prospera test also showed an AUC of 0.91 for differentiating rejection vs. quiescence; however, because quiescence includes only the most stable of patients, and excludes patients with non-rejection pathology findings on biopsy, its utility in a real-world setting is limited. This analysis is similar in concept to that described in recent multi-modality assay validation publications.2,3
"These new data from the Trifecta study clearly demonstrate that Prospera with quantification can accurately predict rejection in kidney transplant recipients with indications for biopsy from a diverse population and is a useful tool for comprehensive evaluation of graft status," said Phil Halloran, M.D., Ph.D.
"The AUC of Prospera with Quantification in this multi-site, prospective study was excellent and confirms Natera’s position as the cfDNA technology leader," said Bernie Tobin, general manager of Natera’s organ health division. "Natera now has the most significant prospective biopsy-matched data in the field of dd-cfDNA in kidney transplant rejection monitoring."
Prospera with Quantification is the only test that provides the absolute quantity of dd-cfDNA and total cfDNA along with donor fraction on every report. Combining these three metrics has been shown to improve sensitivity when evaluating transplant rejection, compared to using dd-cfDNA fraction alone. Other commercially available cfDNA tests that assess transplant rejection only report the fraction of dd-cfDNA.
Natera anticipates the results of the Trifecta study will be published in early 2022.
About the Prospera test
The Prospera test leverages Natera’s core single-nucleotide (SNP)-based massively multiplexed PCR (mmPCR) technology to identify allograft rejection non-invasively and with high precision and accuracy, without the need for prior donor or recipient genotyping. The test works by measuring the fraction of donor-derived cell-free DNA (dd-cfDNA) in the recipient’s blood. It may be used by physicians considering the diagnosis of active rejection, helping to rule in or out this condition when evaluating the need for diagnostic testing or the results of an invasive biopsy. The Prospera test has been clinically and analytically validated for performance regardless of donor relatedness, rejection type, and clinical presentation. It has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.
Natera™ is a leader in personalized genetic testing and diagnostics, transforming how we make critical health care decisions. Our tests help clinicians and their patients protect their health and enable earlier and more targeted interventions that lead to better outcomes. Natera’s tests are validated by more than 80 peer-reviewed studies that demonstrate high accuracy, improving patient care outcomes in oncology, women’s health and organ health. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas and San Carlos, California. For more information, visit www.natera.com.
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 or other studies will support the use of our product offerings, our expectations of the reliability, accuracy and performance of our screening tests, or of the benefits of our screening 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 at www.natera.com/investors and www.sec.gov.
Investor Relations: Mike Brophy, CFO, Natera, Inc., 510-826-2350
Media: Kate Stabrawa, Communications, Natera, Inc., 720-318-4080 firstname.lastname@example.org
- Halloran P, et al. Manuscript in preparation. Anticipated 2022.
- Akalin E, et al. Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation. Kidney360. 2021. doi: 10.34067/KID.0005062021.
- Park S, et al. Combining Blood Gene Expression and Cell-Free DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2021;16(10):1539–1551.
SOURCE Natera, Inc.