It takes a superhuman will, determination and usually a lot of money to make a real change in the way the U.S. health care establishment works – most everyone agrees that the barriers to embracing truly innovative medical ideas are high.
 
Entrenched interests, skeptical regulators, expensive clinical trials…the list of roadblocks to sparks of innovation remain formidable. That’s why even two years after they helped rewrite the rulebook, Mayo Clinic and Madison, Wisconsin-based Exact Sciences Corp. (Nasdaq: EXAS) are still touting the accomplishment of getting their Cologuard home colorectal cancer screening kit out and onto the market.
 
Its inventor, Mayo gastroenterologist Dr. David Ahlquist, and Exact Sciences President and CEO Kevin Conroy, each took to the stage at this month’s Mayo Transform 2016 conference in Rochester to recount to an audience of national health care innovators how the seven-year struggle to get a potentially transformative technology onto the market was ultimately won despite long odds.
 
“There were times when I’d be on the phone with our Mayo partners for our weekly Monday morning calls and I’d think, ‘This is never, ever, ever going to come to life. There’s just too many problems,’” Conroy told the attendees. “But it was the openness and the transparency of our collaboration Mayo and our deep respect for their scientific integrity and rigor that made it happen.”
 
When it gained both FDA approval and Medicare coverage in 2014, Cologuard’s makers heralded the decision as a game-changer in colorectal cancer: The availability of an accurate, non-invasive alternative to colonoscopies for screening purposes. Ahlquist called it a “revolutionary new tool” to detect and prevent colorectal cancer, which is one of most common cancers partly due to patients’ reluctance to undergo colonoscopies.
 
The test allows users to mail fecal samples in to the company for analysis. The Mayo-licensed technology detects hemoglobin, a protein molecule that is a component of blood. It also detects certain mutations associated with colorectal cancer in the DNA of cells shed by colon polyps as stool moves through the large intestine and rectum. Patients with positive test results are advised to undergo a traditional colonoscopy.
 
Colorectal cancer is highly treatable with early detection through screening, but 23 million Americans between 50 and 75 are not getting screened as recommended and, as a result, it remains the second-leading cancer killer in the United States. For those whose cancer is detected at an earlier stage, the five-year survival rate can be greater than 90 percent.
 
“When I first came to Exact Sciences, I had three friends in the 40s who were diagnosed, so I knew it was a big problem,” Conroy said. “It’s a very preventable disease, but only if you can get the screening rate up.”
 
Thus the motivation was there to make a potentially major medical contribution seven years ago when the company began its collaboration with Ahlquist.
 
“Collaboration,” the CEO said, “can transform medicine.”
 
But regulators and many corners of the colorectal cancer medical establishment were extremely wary that a home test could be accurate enough to replace the much-hated colonoscopies. Thus, Exact Sciences was required to conduct a truly massive, $50 million clinical trial, in which more than 10,000 subjects were screened.
 
The trial compared the performance of Cologuard to the fecal immunochemical test (FIT), a commonly used non-invasive screening test that detects blood in the stool. Cologuard accurately detected cancers and advanced adenomas (pre-cancerous polyps) more often than the FIT test. Cologuard detected 92 percent of colorectal cancers and 42 percent of advanced adenomas in the study population, while the FIT screening test detected 74 percent of cancers and 24 percent of advanced adenomas.
 
But even that wasn’t the truly hard part. Conroy said that even with the positive results of the clinical trials, the company couldn’t afford to wait three more years following FDA to also be approved for coverage by Medicare. The novel answer: It applied for simultaneous “parallel” approvals by both agencies under an experimental pilot program instituted as a way to shorten the time it takes to bring innovative new medical technologies to patients by “reducing the interval between FDA marketing approval and Medicare coverage.”
 
And so two years ago, Cologuard was the first medical product ever to win parallel approvals, and thus went down in the history books as a groundbreaker.
 
 In July Exact Sciences announced second-quarter revenues of $21.2 million, a 161 percent increase from the year-earlier totals, with completions of 54,000 tests, up from 21,000 from in Q2 2015. Since its launch, some 41,000 physicians have ordered the test.
 
The biggest lesson he learned about how health care entrepreneurs can break down barriers to innovation, Conroy said, is to have the right partners.
 
“It’s through collaborations like the one we have with Mayo that most truly innovative ideas are coming onto the market,” he said. “It was founded upon a really important principle of, ‘Let’s try and do something really big, let’s try and go after cancer eradication.’ We had a big, aspirational goal.
 
“But besides that, you have to have shared values. The way that for every step along the way, it’s been about scientific integrity. That’s what ultimately made Cologuard come to life.”