NEW YORK (GenomeWeb) – Startup Geneticure and Minneapolis-based healthcare system Fairview have embarked on an 800-patient prospective, randomized-controlled trial to assess whether a pharmacogenetic test allows patients to get their high blood pressure under control faster than when treated according to standard guidelines.
The company — founded in 2014 by former Target Corporation executive Scott Snyder and three researchers with expertise in physiology, cardiology, and genetics — has raised around $1.1 million from angel investors and contributions from Mayo Clinic Business Accelerator, Stanford University, and University of St. Thomas. The proceeds will fund the study that may very well shape up to be the largest prospective RCT for personalization of high blood pressure treatment to date.
In the study, researchers will randomize patients with hypertension to receive treatments either guided by Geneticure's PGx test or according to standard guidelines, and compare the two groups to see which achieves blood pressure control faster, experiences the most reductions, and requires fewer classes of medications to achieve control.
An estimated 80 million adults in the US suffer from hypertension and around half don't have it under control. Current standard of care for high blood pressure usually starts with a diuretic. If this doesn't work even with the highest dose, patients receive a vasodilator, and failing that, a beta blocker. Often, patients are on three kinds of meds, which over time can lead to health complications.
"Patients end up on unnecessary drugs and in a disease like hypertension, where you don't feel pain, there is not a sense of urgency from discomfort or pain to get you back to the doctor," said Geneticure CEO Scott Snyder in an interview. "That's why a lot of patients bail on their therapy."
Although in pharmacogenetics, the mantra is "the right drug for the right patient," in hypertension, how fast a patient's blood pressure is controlled impacts outcomes. Using the standard trial-and-error method, it takes the average patient more than a year, or five office visits, to get his or her high blood pressure under control, but even when patients are taking their meds as prescribed, around 40 percent don't achieve control. Geneticure claims that its PGx test can help control patients’ blood pressures in between two to six weeks.
"In Fairview, we generally do pretty well in our management of hypertension," Dang Tran, VP of medical practice at Fairview Medical Group and principal investigator of the study with Geneticure, said in an interview. The healthcare system currently boasts close to a 90 percent rate of control for hypertension patients, he estimated.
But there are unknowns in the standard of care. What's the right starting medication for patients and what's the right treatment protocol in order to get the patient’s condition under control? There aren't studies that address these questions sufficiently, in Tran's view. "So, I think what we're hoping to do is really see in a randomized way, if we did the genetic testing … can we show that we can get patients to [controlled blood pressure] faster?" he said. "And can we get there with less medications, and by extension, in the course of people's lives, save on the cost of all these medications that people are on?"
The study is Fairview's first foray into exploring genetically-informed personalized medicine. Because Fairview doctors are already doing a good job in controlling their patients' high blood pressure, the RCT design for evaluating Geneticure's PGx test was important for physician acceptance of a genetic test, particularly "from a credibility standpoint," Tran noted.
Consequently, the PGx test will also have to meet a high bar in order to show its utility in clinical practice within Fairview. The Geneticure team didn't shy away from the challenge, Tran said, because it was haunted like many other players in the lab industry by the example of Theranos.
The once highly valued company with a star-studded board sought to revolutionize the lab testing industry with a novel blood-based testing platform, but did not subject the data underlying the technology ahead of market introduction to peer review. Subsequently, federal inspections of Theranos' labs uncovered deficiencies that raised serious questions about the accuracy of its technology and the company shut down its labs.
"I think that's something that really impacted them," Tran said of the leadership at Geneticure and their reasons for conducting a large RCT.
"It is astonishing that in this burgeoning field you have all these so-called personalized medicine companies that are cherry picking genes and going to market with them without any clinical evidence," Snyder said. "We feel very strongly that you're going to have very meager clinical adoption, [because] folks want to see the data."
Geneticure is currently offering its laboratory-developed test commercially through a CLIA-certified lab, and has conducted and published a smaller, retrospective proof-of-concept study. This is not an uncommon strategy in the genetic testing space, although firms have been slow to invest in conducting RCTs to demonstrate clinical utility. Among PGx testing firms, which for years have suffered from a difficult reimbursement climate, several are now starting to do them.
For example, Medicare coverage for Assurex's GeneSight PGx test was based on meta-analysis of three two-armed prospective studies, one of which was an RCT involving 50 patients. The company, recently acquired by Myriad Genetics, is now conducting a 1,200-patient prospective RCT to demonstrate the clinical utility of the test in predicting the right psychotropic treatment for major depressive disorder.
Meanwhile, Geneticure's proof-of-concept trial involved around 100 patients to assess the impact 14 genes involved in drug metabolism and protein function in the kidney, vasculature, and heart, and concluded that SNPs in these genes influence patients' responses to various blood pressure medications. The three researchers who cofounded the company — Ryan Sprissler from the University of Arizona Genetics Core, Thomas Olson from the Mayo Clinic, and Eric Snyder from the University of Minnesota, and the CEO's brother — chose genes that are functional, common, and had been studied extensively in human, cell, and animal models.
That proof-of-concept trial yielded some intriguing findings that warranted further follow up. For example, it showed that although some patients were metabolizing beta-blockers, they still weren't responding to treatment as they should because they lacked a functional receptor. Other patients who had certain functional cardiac genotypes and were on a class of medications that addressed the cardiac system experienced particularly notable reductions in blood pressure.
Geneticure is embarking on the study with Fairview to test if these findings hold up in a larger, prospective, randomized study. The effort, Snyder believes, will be critical for broader adoption of the test and to demonstrate clinical utility for insurance coverage.
He declined to disclose how many doctors have ordered the test to date. The company hasn't published any economic studies yet but estimates that its PGx test can address a hypertension market of 30 million patients and can impart $130 billion in healthcare savings by, for example, helping avoid diuretic-related side effects like stroke and cardiovascular disease.
"No matter how greatly we can improve lives or save lives, it has to be significantly meaningful for those who are paying for care," Snyder said. He wouldn’t discuss the list price of the test but claimed that the test has the potential to yield more than 25 times the return on investment for a payor over a period of eight to 10 years — the time frame when a patient is with the same payor. Upon successful completion of the 800-patient study, Geneticure is hoping to apply for custom CPT codes and achieve pricing at between $500 and $1,500.
"If we fast forward and assume that this trial is successful and it shows this test … guides therapy in a meaningful way, then there will still be a struggle to get a payor to pay for it or a patient to pay for it, or to get another payment source," Tran said. "Over time, as more positive studies come up … it could change the minds of some payors to start to pay for this."
Geneticure, which is currently a nine-person operation, expects to continue to market the test as an LDT through its CLIA-certified and College of American Pathologists- accredited lab. The test is ordered by a physician, who collects a sample from patients via cheek swab and sends it to Geneticure's lab for analysis. As such, the company believes its test is low risk and doesn't need premarket approval from the US Food and Drug Administration, which for the time being is holding off on finalizing its plan to regulate all LDTs.
Snyder said he's had conversations with instrument manufacturers about eventually transitioning the PGx test to the point of care, which then would require the FDA's nod. "That's really where this should be," he said. "As the cost of instruments comes down … there's no reason why these tests shouldn't be on FDA-approved boxes at the point of care."