Trifecta study sets new validation standard for dd-cfDNA in kidney transplant rejection with largest prospective, multisite, fully biopsy-matched study


Statistically significant improvement in performance using both dd-cfDNA fraction and amount of dd-cfDNA compared to dd-cfDNA alone

AUSTIN, TX, June 29, 2022 /PRNewswire/ — Natera, Inc. (NASDAQ: NTRA), a world leader in cell-free DNA (cfDNA) testing, today announced the publication of a manuscript in a leading journal in the field of organ transplantation, Transplantation, validate the performance of a new two-threshold algorithm for its Prospera™ test for the evaluation of transplant rejection. Prospera incorporates donor fraction and estimated amount of donor-derived cfDNA (dd-cfDNA) when assessing active rejection. In the study, Natera’s new method demonstrated significantly improved performance over rejection assessment using the donor fraction alone.

(PRNewsfoto/Natera, Inc.)

The “Trifecta” study, led by the principal investigator Phil Halloran, MD, Ph.D., director of the Alberta Transplant Applied Genomics Center, currently enrolls at 25 sites globally. The first 367 samples from eligible adult kidney transplant recipients were analyzed and included in the manuscript. These samples represent the largest prospective cohort, fully matched by biopsy with dd-cfDNA analysis for kidney transplant recipients performed to date. Assessment of active rejection by the Prospera assay was assessed against RNA-based molecular pathology (Molecular Microscope® Diagnostic System, “MMDX”) and histological assessment (Banff Classification of Allograft Pathology, 2019) of the biopsy. The Trifecta study cohort includes a total of 125 samples with active biopsy-proven rejection by MMDX and 142 samples with biopsy-proven rejection by the BANFF criteria used to compare dd-cfDNA calls, exceeding both 271 samples and the 1132 samples from biopsy-proven active rejections in previous dd-cfDNA testing studies.

The Prospera assay excelled in distinguishing between active rejection and non-rejection, with AUCs of 0.88 assessed with MMDX, 0.82 assessed using BANFF criteria, and AUC of 0.91 versus quiescence. The excellent performance further highlighted the value of Prospera’s two-threshold algorithm, as the combination of dd-cfDNA fraction and estimated dd-cfDNA amount outperformed either variable. alone. The two-threshold algorithm detected six additional cases of rejection compared to using the donor fraction alone.

“This study shows that the performance of the dd-cfDNA assay, using the two-threshold approach, is significantly improved and correlates strongly with other molecular methods such as MMDx,” Dr. Halloran said. “This is a key piece of evidence supporting the routine use of molecular methods to supplement traditional biopsies to diagnose rejection.”

“Our heritage of expertise in cDNA analysis has allowed us to maximize the insights we gain from our testing, providing transplant recipients and their physicians with clinically actionable insights from a single test” , said Sangeeta Bhorade, MD, chief medical officer for organ health at Natera. “The excellent AUC of the Prospera assay in this study establishes the importance of leveraging the combination of the dd-cfDNA fraction and quantification over the donor fraction alone.”

About the Prospera test

The Prospera™ leverages Natera’s 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 genotyping of the donor or the recipient. The test works by measuring the fraction of donor-derived cell-free DNA (dd-cfDNA) in the recipient’s blood. It can be used by physicians considering the diagnosis of active rejection, helping to rule out or rule out this condition when evaluating the need for a diagnostic test or the results of an invasive biopsy. The Prospera test has been clinically and analytically validated for performance regardless of donor relationship, type of rejection and clinical presentation. It was 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 United States Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified and CLIA certified.

About Natera

Natera™ is a global leader in cell-free DNA testing, dedicated to oncology, women’s health and organ health. Our goal is to integrate personalized genetic testing and diagnostics into the standard of care to protect health and inform earlier, more targeted interventions that help lead longer, healthier lives. Natera’s tests are validated by over 100 peer-reviewed publications that demonstrate high accuracy. Natera operates laboratories that are ISO 13485 certified and CAP accredited under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, TX and San Carlos, California. For more information, visit www.natera.com.

Forward-looking statements

All statements other than statements of historical facts contained in this press release are forward-looking statements and do not constitute 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 any 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, than the results of clinical studies or others support the use of our product offerings, the impact of the results of these studies, our expectations regarding the reliability, accuracy, and performance of our tests, or the benefits of our tests and product offerings to patients, providers and payers Additional risks and uncertainties are discussed in more detail under “Risk Factors” in Natera’s recent filings on Forms 10-K and 10-Q and in other filings by Natera with the SEC sometimes. These documents are available at www.natera.com/investors and www.sec.gov.

contacts
Investor Relations: Mike BrophyChief Financial Officer, Natera, Inc., 510-826-2350
Media: Kate StabrawaCommunications, Natera, Inc., [email protected]

References

  1. Bloom RD, Bromberg JS, Poggio ED, et al. Cell-free DNA and active rejection in renal allografts. J Am Soc Nephrol. 2017;28(7):2221-2232.

  2. Bu L, Gupta G, Pai A, et al. Clinical results of the ADMIRAL study (Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance). Kidney Int. 2022;101(4):793-803.

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