NEW YORK ─ Arquer Diagnostics is developing urine-based assays that it believes have the potential to improve health outcomes and streamline the way clinicians treat patients with bladder and endometrial cancers.
In the next few months, the Sunderland, UK-based firm expects to complete the recruitment of patients for a US clinical study to further validate the clinical performance of its first urine test, called ADxbladder, and prepare a submission for 510(k) clearance to the US Food and Drug Administration. The company is simultaneously developing an assay that uses the same biomarker to detect endometrial cancer.
The bladder cancer assay detects antibodies to MCM5, for minichromosome maintenance complex component 5, a protein that is exfoliated into urine in the presence of urothelial carcinoma, and its clearance by the FDA would "open up a number of options" for Arquer, its CEO Nadia Whittley said in an interview.
The company is deciding whether to commercialize and launch the test by itself or seek partnerships with companies that have established sales and marketing channels for IVD tests in the US. In Europe, meanwhile, it has started selling its kits, mainly through distributors.
To detect whether cancer is present or not, Arquer's tests, which are run on broadly-available laboratory-based ELISA platforms, use mouse monoclonal antibodies to detect levels of MCM5 proteins in cells exfoliated into urine.
According to Whittley, its bladder cancer test can help clinicians diagnose patients and monitor them for recurrence. "The unfortunate thing about bladder cancer is that once you've been diagnosed and treated, recurrence rates are high," she noted.
Bladder cancer can return in up to 65 percent of cases, or more, depending on the level of patient risk, and patients already diagnosed and treated have to return for cystoscopy and cytology testing at precise intervals. Given a choice, most patients prefer to avoid cystoscopy, which involves passing a thin tube with a light and camera through the urethra and into the bladder.
Taking the urine test as an alternative to cystoscopy and cytology can streamline testing, reduce the risk of complications for patients, and provide greater confidence in test results for urologists, Whittley said.
Arquer's second assay uses MCM5 as a clinical biomarker to detect endometrial cancer, a condition that often requires invasive procedures, such as transvaginal ultrasound and tissue sampling, for detection. With encouraging results from a UK-based feasibility study, the firm has initiated a clinical study to evaluate and validate the clinical utility of the assay with a view to obtaining CE marking, Whittley said.
Arquer expects to obtain such marking for its endometrial cancer test by the end of next year, and it has plans to launch it soon after, targeting gynecologists who are diagnosing patients suspected of having endometrial cancer.
To obtain regulatory approval in Europe for the new assay, the firm began preparing for new IVD regulations about two years ago, Whittley said. It has been a "complex journey as the bar is much higher on pretty much everything, and companies needed to have a precise strategy or it will be difficult to meet the new standards as they come into play in 2022," she said. "Our endometrial cancer trial has been designed with the new IVDR regulations in mind." Arquer has selected health centers for the study and will start recruiting soon, she added.
The company intends to later seek a US FDA premarket approval for the endometrial cancer test, a different regulatory pathway then for the bladder cancer test, and will probably look to partner with an IVD company to jointly launch the assay in the US, Whittley said.
Whittley added that the clinical need for a non-invasive endometrial cancer test is just as critical as for bladder cancer because of the vast "number of women that undergo unnecessary, invasive, painful, and costly procedures."
For its first-to-market bladder cancer assay, the company has demonstrated in numerous clinical studies that an MCM5-negative test result rules out the presence of bladder cancer with a high level of certainty, and patients can thus avoid invasive follow-up cystoscopy, Whittley said. An MCM5-positive test result means that cancer is likely present, and confirmatory testing including cystoscopy and tissue biopsies is needed.
In clinical studies, its bladder cancer test has been shown to have a negative predictive value of 99 percent for ruling out bladder cancer in high-risk patients, the firm noted. Further, for 95 percent of all patients suspected of having bladder cancer, the test has a negative predictive value of 95 percent, Whittley said.
Thus far, Arquer has demonstrated these results in studies involving more than 1,700 patients, Whittley said, adding that for the current US study involving 650 patients it is including additional ethnic groups, and it will submit data from European and US studies to the FDA.
Additionally, the company intends to seek future regulatory approvals to enable primary care physicians to order its test so that "an enormous number of patients" can avoid having to visit with urologists for cystoscopy and cytology, Whittley said. Arquer has applied for a grant to Innovate UK to support a study to validate the clinical utility of its test in primary care.
The firm launched ADxbladder in Europe in 2018 on the back of an 856-patient clinical trial and subsequent CE marking and had plans to launch the assay in the US in 2020. However, the COVID-19 pandemic derailed those plans, Whittley said, with urologists — the main target for its bladder cancer test — unable to see patients for extended periods.
Nonetheless, with economies reopening, the firm has restarted the launch of the bladder cancer assay, Whittley said. Hospital laboratories in Spain, Italy, and the Netherlands are using Arquer's bladder cancer kit for clinical diagnosis, and eight hospitals in the UK are validating it in their laboratories — a necessary step for its potential implementation.
In the past year and a half, despite the pandemic, Arquer also found a way to make progress with its development work and clinical studies, Whittley noted.
That has involved numerous Zoom meetings with clinical collaborators in 13 health centers for its US bladder cancer study, evidence of US urologists' level of interest in getting its IVD assay to market, Whittley said.
The firm set up the study, trained the health centers, and started recruiting patients using video conferences, and Arquer "will most likely help complete the study without having set foot in the United States," Whittley said.
Arquer can expect competition from companies that are developing or are on the cusp of launching IVD assays using various technologies for bladder cancer detection.
For example, French diagnostic test developer OncoDiag is selling a multiplex, real-time PCR kit to French urologists that it said has a high negative predictive value for patients being treated for low-grade, intermediate-risk, and high-risk of bladder cancer recurrence, and helps urologists decide whether to postpone or proceed with cystoscopy.
Israeli molecular diagnostic firm Nucleix, which raised $55 million in April, believes it can obtain FDA 510(k) clearance later this year for its Bladder EpiCheck assay, which searches for specific methylation patterns on circulating tumor DNA in a patient's blood or urine sample. And UK-based Nonacus and the University of Birmingham recently announced a partnership to develop a noninvasive liquid biopsy assay for bladder cancer detection.
In the US, South San Francisco, California-based Veracyte recently announced that its Decipher bladder cancer assay — which uses gene expression analysis from transurethral resected bladder tumor specimens — will be covered under a future local coverage determination from Medicare. Further, Redwood City, California-based Guardant Health recently reported that its ctDNA technology could detect the presence of bladder cancer, and reported a sensitivity of up to 67 percent.
To support its commercial activities and ongoing test development, Arquer recently launched a new financing round and is looking to raise about $5 million.
In the US, if it obtains regulatory clearance, the company will engage with payors to discuss the requirements for reimbursement. It is researching product pricing for potential US customers, Whittley said. On the other hand, in the UK and other European countries, the firm is working with hospitals that cover the costs of bladder cancer testing. Hospitals in the UK, for example, are primarily funded by the government from general taxation.
Whittley noted that, overall, health systems can obtain substantial cost savings by ruling out cystoscopy, which in the UK, for example, "costs £500 [($685)] to £1,000" per procedure, while the Arquer bladder cancer test costs £40 or less.