By Mary Vanac
Jake Orville always thought the cardiac inflammation biomarker developed by Dr. Stanley Hazen and his colleagues at the Cleveland Clinic was a valuable and proven technology. But his efforts to make it a commercial success for spinoff company PrognostiX failed, largely due to the difficulty of getting the test through clinical trial process required by the Food & Drug Administration.
So Orville, who’s now the president and CEO of another Clinic spinout, Cleveland HeartLab, is looking to commercialize the test for myeloperoxidase — an enzyme that indicates inflammation in the artery walls of the heart, which can predict fatal heart attacks or strokes — via another business model.
Large companies with arrays of diagnostic tests and deep pockets might succeed with such a model, but startups often can’t. PrognostiX burned through its startup cash before it could sell enough tests to support its operations. Orville developed a fee-for-service model, which had succeeded for him at prior companies. Now, Cleveland HeartLab is selling the test as a service of its CLIA-certified and CAP-accredited reference lab.
The trouble with the PrognostiX model was that it was unsustainable, Orville said.
“Putting it in a kit, going to the FDA, launching it, getting key opinion leader adoption, getting mass adoption, and, oh, there’s this thing called reimbursement, right? And then getting it written as a standard of care. That’s a 10-year cycle,” he said.
PrognostiX could accelerate the discovery-to-commercialization part of the cycle with its robust technology, affiliation with the Cleveland Clinic and fast-track FDA approval.
But it couldn’t accelerate the commercialization-to-standard-of-care portion of the cycle, Orville explained.
“So instead of 10 years, you’re at eight. It’s still an unsustainable model for a young, emerging company that has limited funds and resources,” he said.
And he couldn’t even imagine starting the cycle all over again when the company came up with another technology.
“So you’re going back to the same cardiologists and convincing them of the same story,” Orville said. “We’ve learned that getting past the administrative bureaucracy — from when the doctor says, ‘I want it’ to the time it’s implemented — is a Herculean task, especially at major medical centers.”
Offering the test as a service eliminates many of the bureaucratic barriers posed by getting big laboratories to buy and use a test kit, Orville said. Instead, his company is reaching out to an emerging group of lipidologists — community doctors who recognize heart disease as the top risk for their aging patients.
“They’re like sponges,” Orville said. “They want to be knowledgeable about caring for lipid patients.”
Those patients are typically at least 55 years old and have risk factors for heart disease, such as high cholesterol, high blood pressure or a family history of heart problems.
“These are people who want to look beyond traditional risk factors,” he said.
That’s where Hazen’s work comes in. Most doctors realize that cholesterol counts alone give an incomplete picture of heart disease risk. So do measures of non-specific inflammation, such as high sensitivity C-reactive protein.
But myeloperoxidase is part of the process of building up plaque in heart arteries, and it is concentrated in “vulnerable plaque” — deposits that could break away from artery walls and cause heart attack, stroke and death.
“We discovered that MPO plays a role in virtually all facets of the evolution of atherosclerotic plaque, from plaque initiation and development, to development of plaque fissuring and acute heart attack,” said Hazen, who holds a host of titles at the Clinic, including section head of preventive cardiology and rehabilitation and director of the Center for Cardiovascular Diagnostics and Prevention.
The Cleveland Clinic licensed Hazen’s MPO technology to Cleveland HeartLab, which in addition to developing its own test, sub-licensed the technology to Abbott Laboratories and Siemens Healthcare Diagnostics to develop tests for urgent-care settings, such as emergency rooms, said Hazen, who is also chief scientific officer of Cleveland HeartLab.
Hazen sees Cleveland HeartLab’s work as most beneficial in the community screening setting. Myeloperoxidase can identify patients who are at risk for fatal heart attacks when more traditional tests can’t, he said. Hazen recently received $9.2 million more from the National Institutes of Health to continue his study of inflammation in heart disease.
Cleveland HeartLab offers an array of lipid and inflammation tests, Orville said. Only the CardioMPO test is proprietary.
The company recently closed on a $3 million investment round, which it will use to expand sales and marketing, build internal operations and commercialize more Cleveland Clinic technologies. Already, the company has hired four people, for a total staff of 12.
The company competes against Berkeley HeartLab of Burlingame, Calif., a spinoff of Lawrence Berkeley National Lab that was acquired by Celera Group of Rockville, Md., in 2007. Berkeley HeartLab is a reference lab that offers advanced lipid testing, Orville said. His Cleveland company also competes with Atherotech of Birmingham, Ala., whose VAP test is considered the best advanced lipid test, he said.
Then there’s LipoScience in Raleigh, N.C., and its LipoProfile test to measure the number of lipoprotein particles in the blood that form atherosclerotic plaque. But Cleveland HeartLab is the only lab that looks at inflammation markers, Orville said.
“The truth is — and I’m not the doctor — lipids are great to look at. They give you a general state of risk in your body. But it’s inflammation that causes the events,” he said.
“My own father, he’s from upstate New York, walking uphill, shortness of breath. He went to a cardiologist. Normal lipids. Passed the stress test,” Orville said. “Got our panel: Through the roof. Two weeks later, he had a triple bypass at the Cleveland Clinic. He had three completely blocked arteries. My dad was one walk away from a heart attack.”
If patients have a risk factor for heart disease, both Medicare and private insurance generally pay for Cleveland HeartLab’s five-test panel, he said. But even if the insurers don’t pay, the panel costs $180.
In the end, the company also could sell the MPO test directly to physicians and labs.
“That’s the beauty of the model,” Orville said.