NEW YORK (360Dx) – Following on a series of distribution agreements for markets around the world, Israeli molecular diagnostics firm MicroMedic is aiming to expand into the US with its liquid biopsy assay for detecting early-stage urothelial carcinoma.
According to MicroMedic, its CellDetect assay diagnoses bladder cancer in about twenty minutes using a unique plant-based dye that distinguishes between malignant and benign cells.
Symptoms of bladder cancer in patients often include frequent pain while urinating or hematuria. Clinicians normally diagnose bladder cancer after performing a Pap smear on a patient's urine sample. However, Pap staining does not always perform as well when diagnosing bladder cancer in patients, leading to complications such as false positives. Â
Tel Aviv, Israel-based MicroMedic is developing the CellDetect platform, based on a plant extract and three dyes that allow discrimination between malignant (red) and benign (green) cells. The dyes are based on specific metabolic changes linked to cancer cells. After preparing a voided urine sample of about 50 milliliters, researchers can use the cell staining kit with a lab's autostainer tool to produce a smear. Pathologists then observe the sample slide to determine if the patient has bladder cancer.
According to MicroMedic CEO Guy Lerner, researchers only need to wait about 20 to 30 minutes after staining the cells to see if they are cancerous. "This is a relatively easy stain to use, as it doesn't require additional investment in lab equipment," Lerner explained. Â
Founded in 2007 and based on technology developed at the Weizmann Institute of Science in Rehovot, Israel, publicly traded MicroMedic currently has 15 employees. The firm has begun to partner with companies worldwide to distribute CellDetect. While Zetiq Technologies, the firm's completely owned subsidiary, now owns and continues to develop the technology, MicroMedic has begun to partner with companies worldwide to distribute CellDetect. According to Lerner, Zetiq has received at least seven US patents based on the CellDetect technology and dozens more worldwide.
In a validation study published in the Journal of Urology in July 2016, a group of Israeli researchers led by MicroMedic compared CellDetect to standard urine cytology in 217 voided urine samples. After processing the samples into smears and staining a slide of each sample with either Pap or CellDetect, the team found that CellDetect had both an overall clinical sensitivity and specificity of 84 percent to detect urothelial carcinoma. Meanwhile, standard cytology had a sensitivity of 50 percent and specificity of 87 percent. Importantly, the study authors saw that CellDetect "maintained its accuracy irrespective of stage and grade, indicating a putative role in both low- and high-risk disease.
As part of a research poster by Prescient Pharma and Greater Boston Urology at the US and Canadian Academy of Pathology 2018 conference in Vancouver, British Columbia, the researchers presented early validation data on CellDetect's ability to detect early cases of bladder cancer in patients. Using 67 voided urine samples, the team found that CellDetect had near perfect sensitivity and 85 percent specificity, while standard Pap had a sensitivity of 43 percent and specificity of 96 percent. Â
In an additional USCAP 2018 poster presented by John Hopkins University Medicine, the researchers evaluated the performance of CellDetect in the routine screening of 62 patients, who either had hematuria or a history of bladder cancer. The group saw that CellDetect had a near-perfect sensitivity and an average clinical specificity of about 81 percent, whereas standard cytology only identified 50 percent of the positive cases and had a clinical specificity of 98 percent. Â While the researchers noted that using CellDetect in tandem with standard cytomorphology can increase sensitivity of detecting bladder cancer in both surveillance and hematuria screening cohorts, they will need to perform additional validation studies on larger patient cohorts.
Lerner noted that the firm will publish an additional validation study led by the University of Pittsburgh Medical Center at the American Society of Cytopathology in November that highlights CellDetect's improved clinical sensitivity.
Lerner explained that MicroMedic's initial challenge centered around validating CellDetect and presenting convincing results in the US market. The firm now aims to integrate CellDetect into the pathologist's clinical workflow, selling the assay as a laboratory-developed test directly to US CLIA and CAP-accredited labs. As part of its efforts, the firm is actively collaborating with pathologists and urologists to perform research trials, as well as presenting posters at meetings and meeting with key opinion leaders.
MicroMedic is seeking a commercial US partner to fully distribute CellDetect across the US market and hopes to obtain 510(k) clearance from the US Food and Drug Administration by Q4 2019. Lerner declined to comment on the price of CellDetect for end users, as "it changes from one place to another based on quantities," and the type of academic or commercial reference site.
MicroMedic has also started expanding its presence across Europe and Asia, signing distribution agreements for the CE-marked CellDetect test with groups in Greece, Cyprus, Spain, Germany, and Russia. And earlier this month, it signed a distribution deal with Chinese firm Shanghai Gensource Medical Appliances to distribute CellDetect to customers in more than 8,000 hospitals and medical centers in 25 cities across China.
"China is a large market, and … we think [CellDetect] fits the market because they are looking for a low-cost and simple solution that will fit their needs," Lerner explained.
Micromedic will enter a very crowded market as it pushes toward the US bladder cancer diagnostic space with CellDetect. Firm such as MDXHealth and Nulceix now offer their own liquid biopsy-based tools to detect bladder cancer. MDxHealth recently launched its AssureMDx bladder test, which analyzes methylation and mutations in multiple genes, while fellow Israel-based firm Nucleix offers a test called Bladder Epicheck, which uses multiplexed real-time PCR to analyze a panel of 15 methylation markers linked to disease recurrence.
In addition, startup Arquer Dx is preparing a US clinical trial for its AdxBladder test, aiming to launch the test as an aid to bladder cancer recurrence detection and replacement to urine cytology.
Lerner said that CellDetect stands out from other types of staining because of the tool's high sensitivity and ability to accurately diagnose bladder cancer in early stages. In addition, he emphasized that CellDetect can quickly identify cancer cells and does not require the lab to purchase additional equipment for the assay.
According to Lerner, MicroMedic has raised "several millions of dollars" since 2007. BioLight Israeli Life Sciences is the firm's main shareholder, while additional funding has come from angel and public investors.
He added that MicroMedic aims to eventually develop similar tools for other conditions like prostate and lung cancers, but it will need to first improve CellDetect's specificity and then "develop protocols" for the additional assays.