NEW YORK ─ French diagnostic test developer OncoDiag has commenced commercialization of its first test, a multiplex, real-time PCR kit that it developed in response to requests by urologists who were looking for a way to detect bladder cancer recurrence early and reduce the use of painful cystoscopies.
Urologists in France had already started using Urodiag, the firm's mutation and methylation biomarker test, for the early detection of non-muscle-invasive bladder cancers (NMIBC) that comprise about 70 percent of all newly diagnosed bladder cancers.
On the back of CE marking obtained in 2018 and $3 million in recently announced funding, the firm has also begun marketing the Urodiag urine-based kit to urologists throughout Europe, and is sketching longer-term plans to develop additional tests and expand into other regional markets, Claude Hennion, cofounder and CEO of the company, said in an interview.
To develop Urodiag, OncoDiag collaborated with French urologists to obtain urine samples from people with a five-year history of bladder cancer. "As this type of cancer has a very high rate of recidivism, about 80 percent during these five years, we were able to monitor the patients and identify the best biomarkers for predicting recidivism," Hennion said.
The Urodiag kit comprises a single-use disposable unit for urine filtration and a real-time PCR assay to quantify mutation and methylation biomarkers. Specifically, the multiplex assay detects four mutations ─ G372C, R248C, S249C, Y375C ─ that are associated with the FGFR3 gene, and simultaneously quantifies the methylation of HS3ST2, SEPTIN9, and SLIT2.
The test's high negative predictive value for patients being treated for low-grade, intermediate-risk, and high-risk of bladder cancer recurrence helps urologists decide whether to postpone or proceed with cystoscopy, Hennion said.
In 2016, OncoDiag collaborated with urologists in four French hospitals as part of a study published in BMC Cancer that described the analysis of FGFR3 mutations and DNA methylation markers in urine for the diagnosis, surveillance, and risk stratification of patients with NMIBC.
The investigators used allele-specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C and preselected 18 candidate genes reported in the literature as being hypermethylated in cancer. They measured methylation levels by quantitative multiplex-methylation specific PCR, and then selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients.
Last May, Hennion and Jean-Pierre Roperch, director of research and development at OncoDiag, published a study in BMC Medical Genetics that described the development and clinical validation of the Urodiag kit incorporating the biomarkers selected from the earlier study.
One of the test's early adopters, Yann Neuzillet, a urologist at the René Huguenin Hospital in Saint-Cloud, France, near Paris, said he began using Urodiag after hearing about its availability through the Cerba group, a private network of medical analysis laboratories in France. French urologists can request testing for patients at one of the many city laboratories affiliated with Cerba or through a hospital laboratory, said Neuzillet, who is not affiliated with OncoDiag.
For Neuzillet, the diagnostic test's performance, and specifically its "excellent negative predictive value for both high and low-grade tumors," tipped the scale in favor of its use, he said. UroDiag is allowing him and other urologists in clinical practice to decide whether to postpone cystoscopy for patients with negative test results, Neuzillet added.
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. However, cystoscopy is especially important in helping urologists identify the presence of low-grade tumors, which are most difficult to detect, Neuzillet said.
Urinary biomarkers in current IVD tests have demonstrated strong performance in detecting high-grade NMIBC but they do not have the negative predictive value that urologists need to detect low-grade tumors in recurrent bladder cancer, Neuzillet said.
According to OncoDiag, its test has a negative predictive value of 98 percent for patients at low risk, 98 percent for patients at intermediate risk, and 99 percent for patients at high risk.
The negative predictive value of Urodiag exceeds that of current biomarker tests for low-grade tumor recurrence, which is too low to consider postponing cystoscopy, Neuzillet said. With the use of Urodiag to decide on postponing cystoscopy, urologists can expect to see savings in cost and time as well as improvements in patients' quality of life, he noted.
OncoDiag has started booking sales in France and, through collaborations with laboratories, has begun targeting urologists in Italy, Spain, Switzerland, Germany, the UK, and the Middle East. Hennion noted that OncoDiag manufactures its own test kits, and its sales approach in Europe and the Middle East involves selecting one testing laboratory in each country that would sell the test to urologists in exchange for the exclusive right to run Urodiag testing.
The firm will work to obtain reimbursement for its test where possible, Hennion said, adding that to achieve additional traction for Urodiag outside of France, OncoDiag will need to navigate regulatory and reimbursement requirements that vary from country to country. Urodiag's tests are being reimbursed under the French national innovation program in advance of a decision about its long-term national reimbursement. As it awaits the decision, the company will need to continue to validate and demonstrate the clinical utility of the test to convince health authorities and health insurers of its reimbursement merits over the long term, Neuzillet said. The price for the Urodiag bladder cancer recurrence test is €400 ($479).
Hennion said he is also collaborating with urologists and key opinion leaders in his role as a member of the board of the European Association of Urology and looking to have the test included in the European Association of Urology Guidelines on Non-Muscle-Invasive Bladder Cancer, which should speed up its reimbursement in other European countries.
For its entry to US markets, OncoDiag is in discussions with undisclosed diagnostic companies with the aim of jointly pursuing US Food and Drug Administration 510(k) clearance for Urodiag. For US sales of Urodiag, the firm may also collaborate with a US distributor, but Hennion has not yet identified one.
The Miserey, France-based company, founded in 2013, is developing two additional tests for which it is planning sales within the next two years ─ Prostadiag, a tissue-based NGS laboratory test that evaluates the aggressiveness of a patient's prostate cancer, and Colodiag, a blood-based mass spec test for detecting proteins associated with colorectal cancer.
The firm intends to position its prostate cancer test as an alternative to tissue biopsy to detect whether men with confirmed prostate cancer need to proceed to surgery and radiotherapy. OncoDiag is collaborating on its development with The French League Against Cancer, which has case histories and tissue samples from 7,000 men with prostate cancer.
The developers used the samples and NGS to identify a set of 37 genetic mutations associated with prostate cancer aggressivity. Using the panel for testing, urologists will be able to tell patients whether patients can avoid surgery and radiotherapy with a sensitivity and specificity of between 95 and 100 percent, Hennion said.
Meanwhile, the firm is developing Colodiag, third in the company's test pipeline, as an alternative to the current fecal test for general population screening for colorectal cancer, Hennion said.
Clinical trials to validate its tests are advancing slowly, partly because hospitals are prioritizing the detection and treatment of patients with SARS-CoV-2. However, in a preliminary clinical validation study, OncoDiag found that the test can identify whether patients have early colorectal cancer with 95 percent sensitivity and specificity. The firm is targeting the middle of next year to obtain CE marking and launch the test for colorectal cancer screening.
Hennion said he sees Sunderland, UK-based Arquer Diagnostics and Rehovot, Israel-based Nucleix among its closest competitors for Urodiag. Arquer's CE-marked urine-based biomarker test, called AdxBladder, detects bladder cancer recurrence alongside cystoscopy, and Nucleix, which recently raised $55 million, expects to receive FDA 510(k) clearance for its Bladder EpiCheck assay later this year.
The colorectal cancer screening space has a large number of IVD developers, but OncoDiag believes Colodiag can be competitive based on the high levels of sensitivity and specificity it is seeing in preliminary studies, Hennion said.
Because of the recent financing and the beginning of sales for Urodiag, the company is now adequately funded to implement its marketing, sales, and product development plans for the foreseeable future. However, additional investment may eventually be needed, Hennion noted, so that it can support international business development and develop entirely new tests for its product development pipeline.