While the debate over healthcare reform continues to rage in the halls of Congress, IVD companies are working to maximize state-of-the-art care and thus help control costs.

On the science side, researchers, physicians, and pharmaceutical companies are able to develop new methods and new drugs that are proving effective for treating a growing number of diseases including cancer, which is the second leading cause of death in the United States.

While the pressure is on to control costs at all levels of care, the emphasis has turned to prevention and to making sure the latest treatments that are available are used appropriately. In this tough economic climate, IVD companies are working to help personalize medicine, which may be the most effective way to maximize care while keeping costs under control.
Recently, IVD Technology magazine’s editors identified three emerging IVD companies that offer IVD tests that are not only cutting-edge but also cost-effective. One company helps to identify early colon cancer with a simple stool test; another helps to optimize dosage of available oncology and other medicines; and the third helps to identify ovarian cancer patients so that they are sure to get the most appropriate surgery the first time.

The three companies are a good indication of where the IVD industry is headed and how big a role IVDs may play in the future of healthcare in this country.

Polymedco: Simple Stool Test for Colorectal Cancer

Pete Welsh, vice president of Polymedco Inc., (Cortland Manor, NY), believes that the biggest challenge to healthcare today is spiraling costs, and the key to solving this challenge is prevention. That’s why he also believes that IVD companies like his, which provides a fecal test kit for colorectal cancer screening that is easy for patients to use, can help to save the healthcare system.

“I think the marketplace is going to change everything,” he says. “We’ve been running 18% of GDP for healthcare. It’s dysfunctional and doesn’t work. We’re going to run out of money and decisions will have to be made, not as to whom we include in healthcare but how are we going to pay for it. And what are reimbursements going to be? Something has to be done and prevention is key.”

Colorectal cancer is the third leading cause of cancer death in America, with 50,000 deaths each year. Yet when detected early, colorectal cancer is highly treatable, and patients with precancerous polyps or early stage cancers often do not have to follow-up with repeated surgeries and costly radiation and chemotherapy.

Polymedco was founded in 1980 by several people (with less than a half-dozen investors) who had worked together in another diagnostic firm, when the field of immunochemistry was just burgeoning, Welsh says. “We enjoyed a very nice market share, primarily by working with other companies and taking their radioimmunoassays and providing better delivery systems of the patient samples and reagents.”

Polymedco’s expertise was looking at new ideas and bringing them to the market around the world, including in Japan. In the 1990s, Polymedco came across a firm that had an immunological screening test for fecal occult blood. “When we looked at the data that was coming out, we found that that test was significantly more sensitive for human hemoglobin in the stool and was a far better marker to say, ‘Yes, there is blood in the stool, and it represents a problem in the colon,’” Welsh says.

Working with Kaiser Permanente based in California, Polymedco was able to show that its OC-FIT (fecal immunochemical test) CHEK increases compliance with screening for colorectal cancer. Since 2006, Kaiser Permanente has mailed the FIT at-home kits to thousands of its eligible health plan members between the ages of 50 and 80, and followed up with automated phone call reminders. In 2009, it saw compliance increase to 73%, a full 10% higher than the national average. With early detection, Kaiser Permanente has seen often deadly stage four colorectal cancers decrease by 30%.

The success of Kaiser Permanente’s experience with FIT has caught the attention of the medical community and other large institutions including the Cleveland Clinic and MD Anderson Cancer Center in Texas, which are launching similar programs, Welsh says. The American College of Gastroenterology recently acknowledged that OC-FIT was a good screening modality. In conjunction with Lab Corp, “we’re now running FIT at tens of thousands of locations, and that distribution throughout the country creates a huge momentum,” Welsh says.

The at-home screening test does not eliminate the need for colonoscopies, the invasive procedure that is the standard of colorectal cancer screening. It’s the opposite, Welsh says: Physicians will do more colonoscopies; it’s just that they will be doing them on the right patients. With colonoscopies running $4,000-$5,000, making sure they’re done on appropriate patients makes them more cost-effective.

The cost for an OC-FIT CHEK is less than $10. Reimbursement, including from CMS, averages about $21. “If you were to screen 60-90 million people, you may have a cost of $600-900 million. But conversely, you would save $40-50 billion each year, if you were to figure what it would cost to treat those in that population whose cancers were not caught early. It’s a huge savings,” Welsh says.

Polymedco has about 100 employees, but because of its success with its FIT test, it is in an expansion mode. “We’re adding 50 more and perhaps even more in 2011,” Welsh says. “We’re trying to get together implementation teams that will go out in the field and work with clinics, train nurses, and inform doctors on how to get this in the hands of patients. The test for the patient is very easy to use, and the less the patient has to do, the greater the success of the program. As a company, we are focusing our efforts on advancing the outcome of colorectal cancer.”

Saladax: Oncology Dose Management Assays

Imagine a simple blood test that can measure the concentration of a drug in a cancer patient’s blood stream and that can be used by the treating oncologist to determine whether the patient is receiving the optimal dose with the highest therapeutic efficacy and reduced toxicity. The patient also can be tested periodically during the course of treatment to allow for dose adjustment to ensure that optimal drug levels are sustained.

That was Salvatore Salamone’s idea in 2004 when he asked Adrienne Choma if she was interested in pursuing this dream. They both left their full-time positions to start Saladax Biomedical (Bethlehem, PA). Salamone and Choma worked together for many years at Roche Diagnostics, Salamone as vice president of R&D and Choma as vice president of marketing and sales.

Saladax’s first test, My5-FU, is for the measurement of 5-fluorouracil, a chemotherapeutic used to treat colorectal cancer. Today, Saladax has a pipeline of 17 proprietary MyCare drug assays, 13 in the field of oncology and four in the central nervous system disorders category. “Like many oncology drugs, some anti-psychotics and anti-depressants have a narrow therapeutic window and dose limiting toxicity that would benefit from dose management,” says Choma, COO of Saladax.

“We have carefully selected our portfolio based on the clinical relevance of dose management for various drugs and their global market potential,” Choma says. The oncology drugs are used to treat such cancers as colorectal, breast, non small-cell lung, and multiple myeloma.

Saladax licensed its technology underlying the My5-FU test to Myriad Genetics, which markets the test exclusively in the United States under the trade name OnDose. Falco Biosystems is preparing for the launch of the My5-FU assay as exclusive distributors for the Japanese market. The My5-FU assay is CE-marked and being commercialized in Europe.

The biggest challenge Saladax faces is demonstrating to oncologists that there is a better way to manage their patients. The standard of care for dosing chemotherapy drugs is typically based on the patient’s body surface area (BSA). “You and I could have the same BSA, and we would be given the same dose of a chemotherapy drug,” Choma says. “But you may have up to 10 times more or 10 times less in your system based on differences in our metabolisms and other factors such as the size of our tumors, other drugs we’re taking, and the stage of our cancers. There are these and other factors you can’t measure individually, but when taken all together, they translate into a concentration of the drug in your blood stream.”

Choma says that many oncologists were skeptical of the tests at first because it is contrary to the way they were taught to practice medicine. “It is difficult to change long-standing practices even when it has been demonstrated for many years that dosing based on BSA does not correlate well with treatment efficacy.” But once doctors evaluate the My5-FU test and see the level of variability of drug levels among their own patients, “they buy into the concept and say, yes, they could use this help. Our tests are another tool that oncologists can use to refine patient care through objective validation of their clinical judgment.”

Choma believes the timing is right for Saladax’s personalized medicine tests because they improve cancer treatment outcomes cost effectively. “Most of our tests are for widely used generic cancer drugs that have been around for many years. Newer biological drugs used in combination with the older chemotherapeutics enhance outcomes. However, the efficacy of cancer treatment continues to be lowest among all major therapeutic categories. Clinical trials demonstrate that our My5-FU test makes a good drug much better with dose optimization. A phase three randomized study of colorectal cancer patients treated with a common regimen of 5-FU showed that overall survival doubled among patients whose dose was monitored and adjusted during treatment, while serious toxicities were virtually eliminated. These are better results than what is found when expensive biologics are added to the regimen. We believe we can achieve better patient care with less by personalizing the dose of existing drugs.”

Saladax has also partnered with Bristol-Myers Squibb Co. (BMS) to develop biomarkers for certain drugs BMS has in its pipeline. “We are looking to partner with other pharmaceutical companies on other drugs to enhance our portfolio through companion diagnostics collaborations,” Choma says.

Choma, who was one of two founders when the company started at the Ben Franklin TechVentures incubator, believes its future is promising. Saladax is establishing itself as the leader in oncology dose management assays and is bringing new tools to the market. Says Choma, “There are many good drugs on the market and many more in development, but we need to learn how to use them better.”

Vermillion: IVDMIA for Ovarian Cancer

Vermillion (Austin, TX) almost wasn’t. But its CEO, Gail S. Page, is confident that it is stronger for having survived a very tough economic climate and its future is now much brighter.

In 2006, when Page was recruited to build a diagnostics division for a company that developed tools for analyzing proteins, the economy was beginning to sour. By the fall of 2008 and early 2009, when Vermillion was planning to launch a diagnostic test that gynecologists and other physicians could use to determine whether a woman’s ovarian mass was benign or malignant “it was,” Page says, “among the worst of times for small companies because the capital markets were drying up.”

Additionally, the cost of a clinical trial for its diagnostic product, OVA1, was much more than anyone had anticipated. Looking at its finances, Page had to make a hard choice: shut down the company and conduct a fire sale, or proceed under Chapter 11 bankruptcy protection. With the approval of the management team and several board members, Page chose the latter to give Vermillion the breathing room it would need to achieve FDA clearance of OVA1.

Page and the other executives resigned, remaining as consultants and working constantly to save the diagnostic business. They reduced the staff which had gone from 150 to 40 down to three: two technical people and one finance person.
The strategy paid off. In September 2009, Vermillion’s OVA1 became the first and only blood test cleared by FDA to indicate the likelihood of malignancy of an ovarian adnexal mass planned for surgery. Four months later, in January 2010, the U.S. bankruptcy court approved Vermillion’s plan for reorganization.

A number of key moves, including a strategic partnership with Quest Diagnostics, have since helped the novel test company to move forward and grow; it’s up to 26 employees. In March 2010, Vermillion launched OVA1in the United States and relocated the company midyear from California to Texas.

Shortly after its launch, Medicare and other private insurers agreed to reimburse for the test. Adoption that quickly is practically unheard of in the IVD industry, Page says. Page says the diagnostic product has great potential because it fits in with today’s emphasis in healthcare on personalized medicine and cost-effective treatments. “If a woman has ovarian cancer and she is referred to gynecological oncologists to remove her tumor, not only does her chance of survival increase and but also her need for a costly second surgery is reduced,” she says. Ovarian cancer is the fifth leading cause of cancer death in women, with 21,500 new cases diagnosed each year.

“So much of healthcare costs are driven on the treatment side,” Page adds. “Our OVA1 test is a clear example of how diagnostics can help physicians make the best decisions on whether to refer a patient to a specialist for treatment.”

However, Page knows that in today’s highly competitive business environment, having one protein-based In Vitro Diagnostic Multivariate Index Assay (IVDMIA) is not enough. “We definitely want to be a more diversified company from not only a product but also a geographic perspective,” she says. In addition to the next generation of OVA1, the company has in its pipeline a novel test it is developing in collaboration with researchers at Stanford University for stratifying an individual’s risk of developing peripheral artery disease (PAD), which affects up to 12 million Americans each year. The test, VASCLIR, evaluates various biomarkers for PAD and creates an index score. Preliminary results show patients with a high index score are seven times more likely to have PAD than patients with a low index score.

Vermillion also has plans to launch OVA1 internationally. “We’re in the discussion stages, trying to figure out when we’re going to roll out the test in other countries including Mexico, the United Kingdom, and India as well as China, Brazil, and Japan,” Page says. “I’m optimistic that will happen sometime this year.”

Through the bleak times, the possibility of getting nothing from her efforts loomed large, Page says. “But each time I receive a call from an ovarian cancer patient or her family member thanking us for not giving up, it makes all the hard work and the risk worth it.”