Québec City’s DiagnoCure set out with a mission to lead development and provision of diagnostics for cancer detection and management. With three successful diagnostic tests already thriving in a market that most companies would be lucky to breach with one, the company is making good on its goal. What started with the personal laboratory of Dr. Yves Fradet, president and chief medical officer of the company, has grown into a driving force in cancer diagnostics that occupies a critical niche, not only detecting cancer but also aiding the decision making process for its treatment.
DiagnoCure’s success is rooted in Fradet’s fascination with immunology and its applications. A professor at Laval University and a full time clinician, Fradet has been the company’s vice president of research and development as well as its chief medical officer since its inception. After earning his medical degree, Fradet’s interest was piqued by immunology. Entering into specialty training, he chose urology for its immunotherapeutic cancer applications. He also studied patients with kidney transplants from an immunological perspective. After finishing urology training at Laval, Fradet went to Memorial Sloan-Kettering Cancer Centre where he worked with Dr. Willet Whitmore, considered one of the fathers of urologic oncology. Returning to Laval, Fradet established his clinical practice as a urologist/oncologist. He also established a laboratory at the university with funding from the Canadian NCI along with some other agencies in Canada. The lab later received funding from NCI U.S. for bladder cancer research. Among the lab’s early developments was a new set of antibodies targeted toward bladder cancer.
Fradet had the idea to develop tests based on the antibodies and began to think about licensing such tests. He started to work with a reference laboratory in the U.S. that used the antibodies to develop a test to monitor and diagnose patients with bladder cancer. At the same time, Fradet was part of the first BioContact, an annual three day event in Québec that would become one of the biggest biotechnology events in Canada. It was there that Fradet met his first business partners, who were looking for opportunities in the area. In 1994 they formed a company. For a while the newly formed team developed ideas in Fradet’s lab with its funding but soon they decided to create DiagnoCure, a commercial endeavour.
After working on the business plan for one year, DiagnoCure raised a private investment of $6 million in November, 1995. “At that time people believed in the potential of biotech and they were pretty undifferentiated about what it could do,” says Fradet. The company incorporated new projects from the university so that there were a variety of activities going on. A year later, they went public and raised another round of financing.
The year 2000 was a turning point for DiagnoCure. The FDA approved the company’s first product, the ImmunoCyt bladder cancer test and at the same time the company announced its idea of a urine test for prostate cancer. It was opportune timing. “That coincided with the technology bubble. Our stock at that time went from 50 cents and rose rapidly to six dollars in a matter of days, it was amazing.”
Surveying the international scene for technology possibilities, Fradet found a marker called PCA3 in a lab at Nijmegen University in the Netherlands. PCA3 is over expressed in the cells of a cancerous prostate compared to the cells of a normal prostate. DiagnoCure acquired worldwide rights to the gene and its promoter and set to work developing a urine test for the detection of prostate cancer. The PCA3 is a nucleic acid amplification test, which measures PCA3 and PSA RNA as a calibrator for the amount of prostate cells. The resulting ratio of PCA3 over PSA RNA gives the risk of having a positive biopsy. The lower a man’s PCA3, the lower the probability that his biopsy will be positive; the higher his PCA3, the higher the probability that his biopsy will be positive.
The first version of the PCA3 test was an analyte specific reagent for the U.S. market in 2003. The company made a deal with Gen-Probe to develop and commercialize diagnostic applications of the PCA3 marker. They launched the test in Europe in 2006 and despite little marketing there are over 80 publications of studies that clearly show its benefit. More specific than the standard Prostate Specific Antigen blood test, the PCA3 test was recently approved by the FDA as a way to help men that have had a first negative biopsy decide whether they need a further biopsy (as the first may miss cancer). Using a PCA3 cutoff of 25 there is more than a 90 per cent chance that the second biopsy will be negative. “In fact, half of the men have a PCA3 below 25. So in other words, you can save as many as half of the biopsies at 2000 dollars a piece, so it’s cost effective for the patient. It’s a vast improvement,” notes Fradet.
Since its introduction, the PCA3 has had a significant impact on the market. There are multi-centre studies of the PCA3 in Europe that shows the test performs as well in men before their first biopsy. The test was also featured in seven presentations by leading professors and researchers at the 27th annual European Association of Urology (EAU) in Paris earlier this year. Thus, the medical community is aware that the burden of diagnosis and treatment can be reduced through the use of a totally non-invasive urine test. With the FDA approval, granted in February, Gen-Probe now has the ability to market the test to urologists and also, in the US, directly to patients.
DiagnoCure also has a colorectal cancer test that they have made a deal with Signal Genetics to commercialize. The GCC Previstage is a nucleic acid test that examines lymph nodes from tissue that has been cut out at the time of colon cancer surgery. Pathologists typically study this tissue and section lymph nodes to check for cancer cells. The problem is that this type of sampling amounts to less than one per cent of a node’s total volume.
To help decide whether stage 2 cancer patients (indicating a recurrence rate of 15 per cent at 3 years) should receive chemotherapy, the GCC Previstage test takes each lymph node, cuts it in half and extracts the RNA to measure a marker called GCC. There are usually about 15-17 nodes per patient. If more than 10 per cent of the nodes are positive for GCC, patients will have the same recurrence risk of stage 3 cancer patients (meaning a 30 per cent risk of recurrence over 5 years) and should receive chemotherapy. Last June the company concluded a transaction with Signal Genetics, selling their U.S. lab operation for $5.7 million. Signal is funding a 500 patient study needed to further validate the test and give even more confidence to clinicians so they can push to sell it.
Research underway at the moment includes a clinical study to collect samples from bronchial aspirations (the typical lung cancer diagnostic procedure) to develop a lung cancer diagnostic test. Bronchial aspirations are frequently negative or inconclusive. Negative or inconclusive tests also allow cancerous nodules in the lungs to grow before being properly diagnosed. DiagnoCure aims to develop a more sensitive and specific test to better diagnose such nodules and aid decision making. The company hopes to have positive results of a pilot study on a lung cancer diagnostic test by the end of the year.
DiagnoCure is unique in having brought three successful products in the field of molecular diagnostics to market. Their major challenge now is financial backing. “You can have the best test but if you don’t have the money power behind it to change the practice of doctors, it’s a challenge. It is difficult in a diagnostic company because you’re not talking about revenues of tens of thousands of dollars per patient; you’re talking about two hundred dollars per test, for example. You have to have high volume.” Regarding challenges, Fradet says he has learned that management is the key to generating a productive company. Good management, he says, can turn unrealized ideas around and re-adjust them to make good use of money invested in a company. “The challenge is to convince people based on the reputation you have and the potential that you show them of the business model.”
Looking to the future Fradet shifts his attention to personalized medicine. “I think everybody talks about personalized medicine and nowhere more than in cancer.” He explains that in the treatment of cancer, some drugs have worked but the model of giving the same drugs to everybody only benefits a few and the significant difference observed in those few patients skews the data toward giving everybody the same treatment. With subsequent drugs, benefits are limited to a subset of patients. A lot of drugs with the potential to help individuals will never make it to market as they will not improve overall survival of the cohort. “I think we are bound to go to a more personalized approach both in terms of treatment and discovery. If we want to make progress in the fight against cancer we have to be more subtle; we can not just treat everybody the same way and hope that we’ll make major improvements. We can now make major improvements by adapting our treatment to the right person at the right time.”
Fradet sees DiagnoCure taking a significant role in personalized medicine as it emerges. He sees a window of opportunity for DiagnoCure to attract the interest of small players with good ideas and bigger players that need content for their platforms and instrumentations. “I think the next big area will be genetics and molecular diagnostics for cancer. We come with experience and products hopefully at a time when the opportunity will grow in cancer diagnostics.” We can look forward to watching the company grow with the opportunities.
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