NEW YORK – Data published last month in Prostate Cancer and Prostatic Diseases is further building the clinical utility case for Bio-Techne subsidiary Exosome Diagnostics' ExoDx Prostate Test, the company said.
The study was conducted as a follow-up to a clinical utility trial run by the company whose results were published in 2020, also in Prostate Cancer and Prostatic Diseases. In the original study, conducted by Exosome Diagnostics and CareFirst BlueCross/BlueShield of Maryland, data was collected from 1,049 men aged 50 or older who had slightly elevated prostate specific antigen levels. Although all the patients in the study received the ExoDx Prostate test, patients in the blinded control arm didn't get their results and proceeded with the standard-of-care treatment.
The molecular test measures a three-gene expression signature in the urine and uses an algorithm to provide a risk score discriminating between benign or low-grade prostate cancer and high-grade prostate cancer.
That original study found that the group receiving the test results underwent 23 percent more biopsies than the control group, but that biopsies were more appropriately applied and approximately 30 percent more high-grade prostate cancers were found.
In the new study, a retrospective outcome analysis was conducted two-and-a-half years after the original study on 833 patients to see how the test affected their care and outcomes, said Johan Skog, the firm's CSO and senior author on both papers. The researchers assessed clinical pathology outcomes in both study cohorts and compared biopsy deferrals and time to biopsy between study arms for cases with low- or high-risk risk scores.
The authors found that patients who were identified as low risk by the ExoDx test received fewer biopsies, deferred the time to their first biopsy, and were significantly less likely to be diagnosed later with high-grade prostate cancer. The average time from testing to first biopsy was significantly longer in the low-risk cohort that received their results compared to both the high-risk patients in that same group and the low-risk patients in the blinded group. The low-risk patients in the second group couldn't be identified by standard-of-care methods and received a biopsy despite their lower risk.
In addition, low-risk patients who knew their test results were less likely to have biopsies than high-risk patients in the same group, whereas the choice to have a biopsy didn't differ between high- and low-risk patients in the control arm, the researchers noted in the paper. Skog said that this showed that "there's no way for the doctor to identify the low- and high-risk patients with other means," adding the test "provides really unique information that the doctor is not able to deduce from other standard-of-care factors."
According to Skog, this new data further strengthens the utility of the test and shows that doctors who don't provide the test will not have the favorable outcomes seen in this study. Doctors "always want to see that the care for their patient is improved by the utilization of the test, and that is what this study shows," he said.
These results are an interim measurement of a five-year follow-up period, and more results will be analyzed and released in another two-and-a-half years, he noted.
The company is also doing other studies on the test, looking at other indicated uses, and assessing how it could be integrated with magnetic resonance imaging or other biomarkers, Skog said. While this study was focused on the initial screening population of patients with slightly elevated PSA, the firm is doing studies in the active surveillance population as well.
Beyond the prostate cancer test, Exosome Diagnostics has built and is using a multiomic platform to further integrate its liquid biopsy biomarkers, Skog said.
It is co-isolating cell-free DNA and exosomal RNA on one next-generation sequencing-based platform to "build a much better mouse trap" and get access to more molecular information, thereby developing better tests, he said, though he declined to name the NGS instrument on which Exosome Dx is developing its own technology. With the as-yet-unnamed platform, the company can do methylation and mutation analysis on cfDNA, along with mutation detection via RNA transcriptome differential expression analysis with sequencing on the exosomal RNA. It provides "a very unique insight into different types of diseases," he said, and the platform can be applied "in a disease-agnostic way."
The firm's ExoLution Plus Kit is its upfront sample isolation method and has previously been used for improving mutation detection, Skog said, noting the kit enables the entire multiomic platform.
In a paper published in Annals of Oncology in 2017, the company and its research collaborators found that isolating both exosomal RNA and cfDNA could improve EGFR mutation detection in non-small cell lung cancer patients. Using both cfDNA and exosomal RNA resulted in sensitivity of 98 percent for detecting activating EGFR mutations and 90 percent for EGFR T790M mutations, while using circulating tumor DNA by itself had a sensitivity of 82 percent for activating mutations and 84 percent for T790M.
Currently, the platform is being used for internal diagnostic development and is being offered to pharmaceutical partners, though there is no published data on it yet, Skog said. The platform provides a "one-stop shop" to get the most benefit out of a sample, extracting both cfDNA and exosomal RNA in a single step and allowing the company to "get better answers from our biomarkers."
Right now, the firm has diagnostics programs focused on colorectal cancer and other oncology indications, and it is seeing benefits from using the platform to look at both cfDNA and exosomal RNA, rather than traditional liquid biopsy methods of just looking at cfDNA, Skog said. The platform is able to preserve the integrity of what it captures, allowing for small RNA analysis as well as global profiling of messenger RNAs and long noncoding RNAs. The platform has also made it easier to do pathway mapping analysis to understand what disease-associated pathways are being dysregulated in different conditions, he added.
Other diagnostics companies are also using liquid biopsy to analyze both cfDNA and RNA. Cancer diagnostic firm Circulogene offers tests that use next-generation sequencing and PCR to analyze DNA and RNA, while Caris Life Sciences has been developing a blood-based version of its comprehensive genomic profiling service that sequences cfDNA and cfRNA.
Bio-Techne also has programs outside oncology where the platform is being used, such as for neurodegenerative diseases, transplant monitoring, inflammatory diseases, and autoimmune disorders. While Exosome Dx's technology can extract both cfDNA and exosomal RNA, Skog noted that the company is only extracting cfDNA "when it adds value," such as in certain oncology applications where early detection of methylation markers is useful. Many applications, including the ExoDx Prostate test and the ExoTru kidney transplant rejection test, don't include the capture of cfDNA.
The ability to extract "high-quality material" has made it possible for the firm to perform unique analyses and use less common sample types, like cerebrospinal fluid and saliva. Saliva has often been challenging to work with due to microbial contamination, but the company has been able to use its multiomic platform to perform complete RNA transcriptome profiling in a saliva sample, he said.
For example, the firm is using its technology to map and monitor autoimmune pathways that are differentially expressed and dysregulated in the saliva of patients with Sjogren's disease, an autoimmune disorder that affects fluid secretion glands. The company has an ongoing study to profile RNA in saliva samples from Sjogren's disease patients, he noted.
The platform provides a "much broader … toolbox to look at multiple different types of diseases" and helps "solve complex biomarker questions," he said.