The molecular diagnostic services program (MolDx) of Medicare administrative contractor Palmetto GBA has issued a draft local coverage determination (LCD) for the Prospera donor-derived cell-free DNA (cfDNA) test from Natera, San Carlos, Calif, for detecting active rejection in kidney transplant recipients.
The draft LCD represents a major reimbursement milestone on the company’s path to commercialization. In its determination, MolDx writes that “Prospera is an effective, noninvasive method of assessing kidney allograft status with better performance than the current standard of care. The evidence is sufficient to support that Prospera provides a noninvasive assessment tool to assess for the presence of active allograft rejection. The evidence also suppo
rts that Prospera identifies both ABMR [antibody-mediated rejection] and TCMR [T-cell mediated rejection], and it is validated to detect subclinical AR [active rejection].”
Paul Billings, MD, PhD, Natera.
“I am pleased with the draft coverage decision and look forward to working with Medicare to make this test accessible for those in greatest need,” says Paul Billings, MD, PhD, Natera’s chief medical officer.
In the United States, there are more than 190,000 people living with a kidney transplant, and roughly 20,000 new kidney transplant surgeries are performed each year.1,2 It is estimated that 20% to 30% of organ transplants fail within 5 years, and approximately 50% fail within 10 years.3,4
Traditional tools for diagnosing organ transplant rejection are either invasive, requiring a tissue biopsy, or inaccurate, relying on serum creatinine. Such limited diagnostic options has created a strong unmet need for better tools to help optimize immunosuppression levels, avoid unnecessary biopsies, and improve graft survival.
The Prospera test detects allograft rejection noninvasively and with high accuracy by measuring the fraction of donor-derived cfDNA in the patient’s blood, which can spike relative to background recipient cfDNA when the transplanted organ is injured due to immune rejection. The test leverages Natera’s core single-nucleotide polymorphism-based massively multiplexed PCR technology to accurately measure donor-derived cfDNA levels without the need for donor genotyping.
Recently published validation studies show Prospera’s superior precision and clinical accuracy relative to other commercially available donor-derived cfDNA assays.5,6 Prospera is the first assay with high sensitivity to both T-cell mediated and antibody-mediated rejection, and it is the first to detect subclinical rejection, which occurs in 20% to 25% of patients during the first 2 years after transplantation and is considered a major driver of graft failure.5,7,8
The Prospera test is intended to supplement clinical evaluation and management of kidney injury and active rejection in patients who have undergone organ transplantation. It may be used by physicians considering the diagnosis of active rejection, helping to rule-in or rule-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 independent of donor type, rejection type, and clinical presentation. In repeatability and reproducibility studies, it showed superior precision, with a coefficient of variation up to five times better than that of a competitive donor-derived cfDNA assay (1.85% versus 9.2% within run; 1.99% versus 4.5% across runs).6,9 In clinical validation, Natera reported higher sensitivity (89% versus 59%) and higher area under the curve (0.87 versus 0.74) than the competing donor-derived cfDNA assay.5,7
Medicare coverage is available for kidney transplant patients, regardless of age, as either a primary or secondary insurer for a minimum of 36 months following a successful transplant. The draft LCD is posted on the website of the Centers for Medicare and Medicaid Services, and is subject to public comments and further Medicare review before it is finalized.
For further information, visit Natera.
References
- Kidney Disease Statistics for the United States [online]. Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases, 2016. Available at: www.niddk.nih.gov/health-information/health-statistics/kidney-disease. Accessed April 29, 2019.
- Organ donation statistics [online]. Rockville, Md: Health Resources and Services Administration, US Department of Health and Human Services, 2019. Available at: www.organdonor.gov/statistics-stories/statistics.html. Accessed April 29, 2019.
- Stegall MD, Gaston RS, Cosio FG, Matas A. Through a glass darkly: seeking clarity in preventing late kidney transplant failure. J Am Soc Nephrol. 2015;26(1):20–29; doi: 10.1681/asn.2014040378.
- Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant. 2011;11(3):450–462; doi: 10.1111/j.1600-6143.2010.03283.x.
- 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; doi: 10.3390/jcm8010019.
- Altu? 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;Epub ahead of print, February 19, 2019; doi: 10.1097/tp.0000000000002665.
- 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.
- 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(6):1354–1360; doi: 10.1111/j.1600-6143.2005.00830.x.
- 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; doi: 10.1016/j.jmoldx.2016.07.003.
