NEW YORK – With its combination immunoassay and qPCR blood test, Mursla Bio intends to identify liver cancers earlier by detecting microRNA and protein targets within extracellular vesicles.
Last week, Mursla announced that it had received US Food and Drug Administration breakthrough device designation for the test, called EvoLiver, which is comprised of a magnetic bead-based immunocapture assay that targets four surface proteins of hepatocyte-derived extracellular vesicles to isolate them from the other sample contents, an immunoassay that targets three surface proteins and is used to quantify concentrations of protein epitopes, a qPCR-based test for the detection of six miRNA biomarkers of hepatocellular carcinoma (HCC), and an algorithm for the analysis and scoring of the results.
The immunoassay is an ELISA-type test that is adapted to the detection of EV proteins, and it uses an optical plate reader for the quantitative determination of proteins of interest on the EV surface. That assay and the qPCR test are both used to measure expression levels of miRNA and protein biomarkers, while the test's algorithm is used to analyze the results and deliver a yes/no result to indicate the likely presence or absence of liver cancer.
According to Mursla Founder and CEO Pierre Arsѐne, the company's EvoLiver test is used for the surveillance of patients with cirrhosis who are at elevated risk of HCC, with the results used to help determine who should proceed to confirmatory imaging using MRI. The test, he said, could help to address the sensitivity issues with existing standard-of-care methods of detecting HCC, particularly in its early stages.
HCC is the most common type of liver cancer, typically resulting from cirrhosis. Patients at elevated risk may be monitored with serum alpha-fetoprotein (AFP) tests and ultrasound, and diagnosis can be aided by liver function tests, imaging, and liver biopsy.
Extracellular vesicles, or EVs, are membrane-bound particles that are released by both benign and cancerous cells and are involved in various physiological and pathological processes. Arsѐne noted that liver-specific EVs comprise a tiny minority of the total EVs circulating in blood, so EvoLiver's immunocapture step is needed to separate the signal from noise ahead of testing for the biomarkers of cancer. The immunocapture and qPCR portions of the test are both performed on commercially available instruments that can provide high-throughput and scalable testing, with results within 24 hours of receiving the sample.
Arsѐne was previously a researcher into EVs, biophysics, and nanoelectronics at the University of Cambridge, and he founded Mursla Bio to retain the intellectual property he developed during his studies, the company said on its website.
Ghassan Abou-Alfa, an oncologist at Memorial Sloan Kettering Cancer Center, said that patients are typically monitored for HCC if they have risk factors such as hepatitis B/C infection, chronic inflammation related to a metabolic disorder, obesity with diabetes, or high alcohol consumption. Ultrasound and AFP have sensitivity issues, though, and patients tend to grow weary of repeated visits for ultrasound examinations and fall out of the recommended screening regimen, he said.
Abou-Alfa, who is not connected with Mursla Bio, is part of a research team that reported in 2023 that it had developed a next-generation sequencing-based test for tumor-derived circulating cfDNA to aid the diagnosis, prognosis, and treatment of HCC patients. He said that cfDNA tests depend on the identification of a genetic signature that is shed by tumors, and the detection of those signatures can be inconsistent.
EVs, though, are abundant in the bloodstream and they contain DNA, RNA, proteins, and lipids that can provide additional information on a patient's liver cancer. He also noted that a blood test provides a simpler option compared to ultrasound, and he thinks that it could help patients to adhere to the recommended testing schedule.
Abou-Alfa said that he sees potential in Mursla's approach. By identifying cancers earlier, such a test could help to save lives, reduce treatment costs, and reduce long-term harm to patients.
HCC is typically identified in later stages, and a multi-institution US team said in a 2023 commentary in the Journal of the National Cancer Institute's Cancer Spectrum that this is partly due to the suboptimal performance of current HCC surveillance methods. Even when ultrasound and AFP are used together, the combination has a sensitivity of only 63 percent for the detection of early-stage cancers, the authors wrote.
They noted, though, that recent study results have shown that other tests for RNA, protein, methylated DNA, and ctDNA targets could provide improved sensitivity and specificity for early-stage HCC. Further, they said that a few studies have provided emerging evidence in support of the use of EV-based biomarkers in HCC surveillance.
The authors of a 2021 review article in Cancers also noted that multiple studies had already produced promising results from the use of miRNA panels to identify patients with HCC and differentiate them from patients with other liver diseases. EVs mediate the pathogenesis and progression process of HCC by regulating the microenvironment and signal pathways for normal and cancerous cells, and tests for EVs and their contents could improve on the existing methods of detecting early-stage HCCs, they said.
Mursla reported in November in an abstract for a meeting of the American Association for the Study of Liver Diseases that data from its MEV01 multicenter clinical trial showed that EvoLiver was used to detect early-stage HCC with 86 percent sensitivity and 88 percent specificity. The study involved the use of 464 prospective and retrospective samples from patients at six European healthcare centers with HCC and cirrhosis.
Arsѐne said that the test uses hepatocyte-specific biomarkers to provide high specificity and HCC-specific biomarkers for high sensitivity.
The firm reported in the abstract that it had analyzed the differential expression of biomarkers from hepatocyte-derived EVs in patients with cirrhosis or HCC, with the aid of mass spectrometry to identify proteins and RNA sequencing to identify miRNA biomarkers. Arsѐne noted that the potential biomarkers were initially comprised of 30 proteins and 51 miRNA targets, and company researchers narrowed the results to the nine markers that were the most promising for the identification of HCC with greater sensitivity and specificity in comparison with ultrasound and AFP.
He said that a full manuscript of the findings will be published in the coming months. For now, he declined to disclose the proprietary list of nine biomarkers in EvoLiver but said that seven have been previously established to have relevance to HCC. He noted that the company's results so far show agreement between the discovery methods and the clinical assay that uses qPCR for the target miRNA and ELISA-like methods for the detection of target proteins.
Other firms, meanwhile, have been making moves in the liver cancer testing space.
Helio Genomics has developed a test that uses cfDNA methylation analysis with machine learning-developed algorithms to identify cancer in its earliest stages, and company officials said last month that they were preparing to submit data from the firm's CLiMB trial to the FDA in support of an application for approval of the test as an in vitro diagnostic. The firm currently offers its HelioLiver test through a partnership with Fulgent Genetics.
Early cancer detection firm Insighta also said last fall that it had begun clinical trials in China for the use of its tests to detect liver cancer through DNA methylation aberrations in cfDNA. Research teams also have in recent years reported promising results from the use of tests for circulating cfDNA fragments in blood and ctDNA biomarkers in urine.
In addition, liver cancer has been a common target among many multi-cancer early detection (MCED) test developers.
Mursla, which has offices in Cambridge, UK, and Cambridge, Massachusetts, is planning to establish this year a US laboratory, likely on the East Coast, to support the launch of EvoLiver as a laboratory-developed test while it continues to pursue FDA premarket approval. The firm plans to secure Clinical Laboratory Improvement Amendments certification ahead of the commercial launch of the LDT, which will likely come in the second half of 2026, Arsѐne said.
"The LDT is a starting point to sell the test, and the FDA is helping you to increase your market reach," he said.
Meanwhile, the firm also plans to conduct a clinical study with chronic liver disease care centers to support reimbursement for the test. While Arsѐne declined to release estimated pricing for the test, he said that the use of the test is expected to reduce healthcare spending through earlier cancer detection.
The firm plans to eventually pursue certification for the test under the EU's In Vitro Diagnostic Regulation certification, although Arsѐne said that it is focusing for now on the US market.