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CareDx Prepares KidneyCare for Commercial Launch With CLIA Validation, Clinical Studies


NEW YORK – CareDx recently published two studies, one showing clinical validation for its recently CLIA-validated AlloMap Kidney gene expression test for kidney transplant rejection and another demonstrating long-term performance results for AlloSure Kidney, its donor-derived cell-free DNA assay for post-transplant injury.

The studies contribute to the company's planned commercial launch of its KidneyCare multimodal kidney transplant testing package. Together, AlloMap Kidney and AlloSure Kidney are expected to provide clinicians with sensitive readouts of immune quiescence and graft rejection risk, complementing histology and other surveillance methods.

"By having a noninvasive tool like AlloSure or AlloMap, you start to get a picture into how this patient is doing," Sasha King, chief marketing officer for CareDx, said in an interview. "You can identify who should go on to have invasive biopsies rather than giving them to everybody, and you're able to better manage the care of these patients."

An exact timeline to commercial launch remains unavailable, while CareDx seeks regulatory approvals for KidneyCare from New York State and a reimbursement decision from MolDX and Medicare. In support of this, KidneyCare is being evaluated in the ongoing Outcomes of KidneyCare in Renal Allografts registry taking place across 50 transplant centers.

KidneyCare will add to the company's line of transplant care products, such as HeartCare, which the company launched in October 2020.

In a clinical validation study, published in Kidney360 in late December, AlloMap Kidney distinguished between antibody- and T cell-mediated rejection, or ABMR and TCMR, respectively, in two patient cohorts. One cohort comprised 98 quiescence samples and 18 rejection samples, comprising seven TCMR samples, 10 ABMR, and one mixed sample.

The second cohort included eight quiescence and 11 rejection samples: seven TCMR, two ABMR, and two mixed.

Using a five-gene classifier consisting of DCAF12, MARCH8, FLT3, IL1R2, and PDCD1, AlloMap Kidney consistently differentiated between rejection and quiescence. Investigators' ability to discriminate between those outcomes further improved when using AlloSure Kidney to evaluate donor-derived cell-free DNA, or dd-cfDNA, alongside AlloMap Kidney.

At roughly the same time the AlloMap Kidney validation study was finishing, CareDx was also wrapping up ADMIRAL, an observational study to assess the long-term performance of AlloSure Kidney as a transplant surveillance tool.

ADMIRAL evaluated the associations between dd-cfDNA and histologic evidence of allograft rejection from 1,092 kidney transplant patients over a three-year period, results that were also published in December in Kidney International.

The assay discriminated between biopsies showing no rejection, any rejection, ABMR, and TCMR, showing that a 1 percent increase in dd-cfDNA associated with an overall 3.3-fold increase in the risk of any kind of graft rejection. Importantly, the assay detected both clinically evident and subclinical ABMR and TCMR, contributing to the assay's ability to provide early warning signs of possible graft rejection.

This, the study's authors argued, makes AlloSure Kidney "significantly more predictive" than serum creatine measurements, the current standard of care. Although rises in serum creatine accompany graft injury, they are not specific to them.

The study further showed that a 0.5 percent increase in dd-cfDNA or greater correlated with an almost threefold higher risk of donor-specific antibody formation, with dd-cfDNA levels rising a median of 91 days prior to DSA detection.

Finally, elevated dd-cfDNA was associated with significant declines in estimated glomerular filtration rate, or eGFR, a measure of the kidneys' ability to filter blood, at three years post-transplant. Persistently elevated dd-cfDNA, meaning more than a single result showing at least a 0.5 percent increase, nearly doubled the risk of experiencing a 25 percent eGFR decline.

"There have been a number of utility studies published now on AlloSure," King said, "but ADMIRAL is really the largest and the first to be sized in a surveillance population."

Validation studies, King went on to explain, take place more often in populations already with the phenotype of interest (such as graft rejection) or use biobanks due to the challenge of getting enough rejections to achieve statistical significance.

"Now we're able to see in a utility study with patients that are surveillance-tested with AlloSure, that the performance characteristics really hold up nicely," King said.

CareDx's next step is to seek licensure for KidneyCare, which combines AlloMap and AlloSure, in New York State, King said.

New York State-licensed laboratories are exempt from CLIA requirements for six years as long as they possess a valid permit under the New York State Public Health Law.

From there, CareDx plans to go to MolDX, the molecular diagnostic reimbursement program administered by Palmetto GBA, after which the company hopes to fully launch KidneyCare pending Medicare coverage approval, King added.

"One thing that is very unique about the kidney transplant space," she said, "is that 80 percent of kidney transplant patients are covered by Medicare."

For now, CareDx only plans to launch KidneyCare within the US, but the company won't rule out the possibility of expanding overseas, should interest grow there. At present, CareDx's only overseas offering is the pan-organ AlloSeq cfDNA, a targeted NGS assay used to measure a transplant recipient's fraction of dd-cfDNA.

CareDx has been making inroads in applying its AlloSure and AlloMap methodologies to surveilling other organ transplants as well. A recent study by the National Institutes of Health determined that AlloSure Lung identified lung transplant rejection more effectively than a diagnostic bronchoscopy, and the company has partnered with three cell therapy biopharmaceuticals to test AlloCell in people receiving allogeneic cell therapies for cancers and other autoimmune disorders.

The company also continues to enroll liver transplant patients into a longitudinal and prospective study comparing the outcomes of LiverCare post-transplant surveillance with standard-of-care strategies.

"We're still in data collection mode," King said about that study, adding that there is not yet a clear timeline on when to expect results to be announced.

The CLIA validation for AlloMap Kidney caps a record year for CareDx, which last week estimated 2021 revenues of $78.6 million to $79 million, representing year-over-year growth of 34 to 35 percent, with record testing volumes and the acquisitions of medication safety and adherence companies MedActionPlan and The Transplant Pharmacy.