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Numares Aims to Eliminate Tissue Biopsy to Detect Kidney Transplant Rejection Risk


NEW YORK (360Dx) – A urine-based diagnostic test for kidney transplant rejection provides new options for nephrologists who normally need to do tissue biopsies that are painful for patients, according to its maker.

The Numares renalTX-Score test employs four biomarkers — alanine, citrate, lactate, and urea — and eliminates the need for a tissue biopsy on patients, the firm, Numares, said.

Individually they are “mediocre biomarkers,” but taken in tandem they provide a robust evaluation of the risk for kidney rejection, Numares CTO Maximilian Zucker said in an interview.

The test is the first available that evaluates a metabolic biomarker network for the diagnosis of an acute rejection reaction after a kidney transplant, he said.

The test is CE marked and has been launched on the European market, but Numares' executives are uncertain about the timing of its release in the US. They are preparing a submission to the US Food and Drug Administration and deciding whether to pursue premarket or de novo clearance, and it could be up to two years before the test has been cleared for use in the US, Zucker said.

Numares noted that the test utilizes the effects of disease on the dynamics of human metabolism, and those effects are recognized as biomarker network changes derived from altered metabolic processes. The biomarker assay runs on the firm's Axinon in vitro diagnostics platform, which employs nuclear magnetic resonance spectroscopy to generate a numeric spectrum.

A urine test for the risk of kidney rejection is especially important because rejection reactions are frequently symptom-free, making diagnoses challenging for physicians. Without the use of the Numares test, a physician must use intuition to ascertain whether there might be a rejection reaction ongoing, and they could then decide to do a tissue biopsy, Zucker said. However, kidney tissue biopsies are painful, requiring insertion of a needle into the kidney and taking a piece of tissue that is then histologically analyzed. "It's clear that this is not at all a good idea for the patient," he said. "It may harm the kidney, and it is expensive."

A nephrologist could try to avoid doing a tissue biopsy, he said, by measuring the patient's level of creatinine, which is used to evaluate kidney function. But creatinine, a single biomarker, is not useful for detecting kidney rejection, Zucker said. Nonetheless, a serum-based creatinine test used in combination with the Numares test provides additional information and "even better results" to the attending nephrologist than using the Numares test by itself, he noted.

Volker Pfahlert, chairman of the executive board at Numares, said in a statement that because the firm's test can be seamlessly integrated into clinical routines, is easy to handle, and delivers fast results, it should be part of the standard repertoire of follow-on checkups within every transplant center in Europe.

More kidneys are transplanted than any other organ. Around 80,000 are transplanted per year globally, Numares said, adding that around 10 percent of these are affected by rejection reactions within the first year. There is a great need for early detection and rapid therapy to mitigate transplant rejection, Zucker said, adding that, "If you consider that each transplanted patient should receive five to seven follow-up tests, you get an idea of the size of the total available market."

As adoption expands, Numares expects that the new test will incrementally begin to replace traditional tissue biopsies and histology testing.

"We are confident that we can replace at least some of the tissue biopsy tests at this point," Zucker said.

The group expects that nephrologists who work in hospitals and operate their own private practices will be the primary targets for using the test. Healthcare providers in a transplant center monitor patients for a few weeks immediately following the procedure, and the patient may then decide to continue to attend the center for follow-up testing, or visit with a nephrologist located closer to where the patient resides.

"We are targeting both the transplantation centers and nephrologists who are out in the field monitoring patients for potential kidney rejection after a transplant," Numares CMO Philipp Pagel said.

Numares prepared the test for CE marking by conducting a clinical study at the transplant center at Regensburg University Hospital in Germany. The firm developed the test in collaboration with Bernhard Banas, head of the transplant center.

"We enrolled 109 patients in the aftercare program of the center, and tested around 2000 samples," Pagel said. Of those, 1300 were "in the target window," for potential kidney rejection, and were used as a basis for analyzing the test. The team spent two years recruiting patients and conducted follow-up testing over a year, and then completed data analysis, he added.

"You can tune the test to be more sensitive or specific depending on whether you are testing to rule in or rule out kidney rejection," Zucker said, adding that at the top of the range, the test has a sensitivity of 90 percent and a specificity of 85 percent.

In designing the test system, Numares developed technology to smooth out technical challenges related to reproducibility with the NMR technology that enables its system. Nuclear magnetic resonance has long been used as a research tool, in particular for determining the structure of chemical compounds, Numares said. However, when it had been applied to tests, results had not been reproducible.

The firm, therefore, developed a magnetic group signaling technology that "tuned the system so that it achieves standardized results," Zucker said.

The firm has a "broad pipeline" of planned tests for use on the system including a urine-based assay for bladder cancer diagnosis and a separate assay that's in development for diagnosing multiple sclerosis. Besides the kidney transplant rejection test, the firm is marketing a CE-marked lipoprotein assay that runs on its system for cardiac disease detection.

"In the long run, we expect to have a large portfolio of different diagnostic tests based on metabolomics and on using serum or urine samples on the same platform," Pagel said.

They noted that they were not aware of any competitors for their kidney transplant rejection test.