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Swedish Transplant Monitoring Firm Devyser Eyes US Market, Beginning With Multi-Donor Study


NEW YORK – Swedish transplant diagnostics company Devyser continues its push into the US solid organ transplant market with the recent publication of a study demonstrating the ability of its One Lambda Devyser Accept cfDNA kit to discriminate donor-derived, cell-free DNA (dd-cfDNA) from multiple kidney donors in a single recipient.

In the study, published last month in Frontiers in Immunology, the company investigated the ability of the next-generation sequencing (NGS)-based One Lambda assay to accurately identify the source of dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations.

The Stockholm-based company is planning further tests of the assay's clinical validity and utility in kidney transplant monitoring, as well as in other solid organ transplant indications, while preparing to eventually seek regulatory approval in the US. Devyser recently established a CLIA-certified lab in Atlanta, which company CSO Michael Uhlin described as the "spearhead" for future expansion into the US.

"We're trying to learn the US market as quickly as possible," Uhlin said.

Differentiating between dd-cfDNA from first and second kidney transplants is crucial for accurate monitoring and diagnosis, as the source of elevated dd-cfDNA levels can indicate whether graft damage was already present at the time of detection of donor-specific antibodies, while the pattern and kinetics of the dd-cfDNA elevation can indicate the type of graft injury that is occurring. 

"This is very important," Uhlin said, "because if you see that [elevated] cell-free DNA is from the kidney you just put in, it would indicate a potential reaction."

Robert Woodward, CSO of CareDx, a potential Devyser competitor, explained that monitoring graft-related dd-cfDNA is also a high medical need because the half-life of a kidney transplant is roughly between 10 and 15 years.

"I think the primary thing that physicians are concerned about is that while you had a kidney from another individual for those many years," Woodward said, "you may have developed additional antibodies to antigens that are not self, so [those patients] have a harder time finding a match."

In Devyser's recent study, the company and collaborators at University Hospital Zurich first affirmed the technical accuracy of the One Lambda assay in artificial dilution series composed of mixed donor DNA. They next assessed samples from 31 patients who had undergone two kidney transplants. The researchers found detectable dd-cfDNA markers from at least one donor in 30 of these patients and from both donors in six patients.

Uhlin noted that the company will now evaluate what these "very important findings" mean for Devyser's IVDR certification, which the company received last year for the One Lambda Devyser Accept cfDNA and One Lambda Devyser Chimerism tests.

The amount of donor DNA markers varied with time. In one case, for example, earlier samples taken from one patient showed undetectable dd-cfDNA levels from the first kidney donor, while later samples were dd-cfDNA positive, indicating that dd-cfDNA levels can fluctuate in the setting of a nonfunctioning prior kidney transplant.

In another example, the researchers detected dd-cfDNA from one patient's first transplant, which had been removed eight years before that plasma sample was obtained, demonstrating that donor cells able to release dd-cfDNA were still present in the patient.

"There was this continuous secretion of a cell-free DNA, even when the organ hasn't been there for a very long time," Uhlin said. "What the biologic impact of that is, we can only guess."

Uhlin cautioned, however, that Devyser's team did not detect dd-cfDNA from the first transplant in the remaining 13 patients whose first transplants had been removed, suggesting that such an event may be uncommon.

"This paper is a good example of [how] we are lifting the lid on the biology of [transplants]," Uhlin commented. 

The current study took place in Switzerland, and Uhlin said that Devyser plans to show the clinical validity of the assay in prospective studies that will include sites within the US.

Last year, Devyser inked an agreement granting Thermo Fisher Scientific exclusive rights to commercialize the One Lambda Devyser Accept cfDNA test, along with the One Lambda Devyser Chimerism test for early detection of stem cell transplant rejection, in Europe, North America, and Brazil.

The company also recently partnered with Illumina to use its MiSeqDx sequencer to advance Devyser's tests through regulatory processes in the US and in Europe. While Uhlin said that the deal with Thermo Fisher is currently only a distribution partnership, Devyser may also consider partnering with them to gain US regulatory approval for the One Lambda Devyser Accept cfDNA test.

In addition to kidney transplants, Devyser is studying the use of its technology in lung, heart, and liver indications.

Whenever the One Lambda Devyser Accept cfDNA test reaches the US market, it will face competition from CareDx and Natera, both of whom offer their own NGS-based assays, which can also be used to identify the organ at issue in multiple allograft settings.

Woodward commented that CareDx, for instance, along with academic collaborators, published a small study in 2019 showing its AlloSure test detected the correlation of higher dd-cfDNA levels with multiple allografts.

Woodward said that the study also showed that rejection identification based on higher AlloSure dd-cfDNA levels was similar in both single and repeat kidney transplant patients, and that all instances of rejection evaluated in the study came from the most recent transplant.

"None of the data we have seen published or reviewed is relative to the prior transplant," he said.

Uhlin expressed optimism at the eventual US regulatory approval and commercial uptake of Devyser's kits, touting the combination of the kits with software to analyze the results, which he said "makes [them] very easy to use."

"With this setup," he said, "it makes it possible for [someone] in a university laboratory to do the analysis."

Ultimately, Uhlin explained, the company wants its products in hospital laboratories, where the need for fast turnarounds mean that those end users should not have to depend on sending samples away for analysis.

"We have built a solid ground in Europe," Uhlin said, "but for us, a big part of the future is the US, and that's why we're going to focus our resources on establishing ourselves there."