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Despite Challenges in the Field, GnomeDx Sees Right Time to Launch New PGx Company

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NEW YORK (GenomeWeb) – After almost a year of early, under-the-radar operations, GnomeDx has officially launched its pharmacogenomics testing services with a focus on cardiovascular disease risk.

Based in Powell, Ohio, and launched this year by parent company Phylogeny, GnomeDx currently offers a series of cardiovascular-specific test options — individual tests for response markers for warfarin, clopidogrel, and statins, and a larger test covering all three. The company also furnishes a broader PGx panel that includes variants associated with response to 180 different medications, as well as services to compile and run customized panels.

Adel Mikhail, Gnome's founder, told GenomeWeb that the impetus for he and the other scientists involved in founding the company came from interest expressed by members of the cardiology community, and a sense that the field shouldn’t have to wait any longer for PGx.

"What you always hear is that pharmacogenomics is about to explode, but it hasn't exploded yet," he said.

"Everyone talks about it, but if you ask about how many patients actually get tested it's a miniscule number. It's more marketing than implementation today, and that is the most frustrating thing for us. … Patients are dying and we have a technology that could be of dramatic value, and we are still not implementing it," said Mikhail.

Indeed, despite years of excitement about the benefits of personalized medicine, the field has so far faced significant challenges in gaining payment for genetic tests that predict patients' responses to commonly prescribed drugs.

"One advantage of a small company is you can act fast. We got tired of talking and decided to do something about it … because [this is] a significant need for both patient care and healthcare costs," Mikhail said.

After deciding to start a PGx company, Mikhail and colleagues spent about two and a half years, he said, validating their technology — which is currently PCR-based — and working out the practicalities of setting up a company. GnomeDx began testing at the beginning of this year, but treated the first several months of operations as a pilot period, only announcing its commercial launch last week.

The company has centered its testing around cardiovascular drugs, such as anticoagulants Coumdain (warfarin) and Plavix (clopidogrel), even adding some markers associated with more general disease risk in addition to drug response.

"The plan from the beginning was in cardiology, because the validation and the value we can offer to cardiovascular patients is the most dramatic," Mikhail said. "You can save patients' lives by evaluating what dose of Coumadin they really should be taking or whether they will actually respond to Plavix."

Coumadin alone is responsible for a significant amount of hospitalizations for strokes, heart attacks, and pulmonary embolisms, Mikhail noted. "These are not simple adverse responses, they are dire responses," he added.

On the Plavix side, he said, "there is data that suggests that to save one patient from [severe complications], you only have to test eight patients taking the drug."

GnomeDx sells three separate cardiac-specific tests – one focused on predicting response to warfarin, one for Plavix, and one for statins. If patients opt for the full comprehensive panel, it covers 12 genes associated with response to almost 200 drugs across many disease areas.

Mikhail said that the pricing situation for GnomeDx is somewhat complicated. If Medicare reimbursed for the company's full panel at the maximum allowable by the fee schedule in Ohio, Mikhail said that the total price would be $1,100. However, Medicare currently does not reimburse the company's full panel (or any comprehensive PGx panels for cardiology). Mikhail did not detail how the company negotiates seeking reimbursement for single variants.

Medicare has hesitated to recognize a clinical benefit or health economic benefits in most PGx associations, despite the acknowledgement of the clinical validity of these associations by the FDA in hundreds of drug labels.

For example, beneficiaries are covered for CYP2C19 testing to guide treatment with Plavix in limited indications. Medicare will not, however, pay for testing of SLCO1B1, which is associated with response to statins, or for non-investigational testing of CYP2C9 or VKORC1 alleles to predict warfarin responsiveness, maintaining that studies to date haven't definitely shown that PGx testing in this context improves patients' outcomes in terms of bleeding risk and hospitalizations. Private insurance coverage meanwhile varies by company.

Researchers and PGx companies have been working to address the lack of utility and health econonic evidence in the eyes of payors. For example, a large pharmacogenetic analysis published in The Lancet earlier this year showed that atrial fibrillation patients with certain CYP2C9 and VKORC1 genotypes are at heightened risk for bleeding during the first 90 days of starting treatment with warfarin and could avoid these adverse events if they instead receive a newer drug called Savaysa (edoxaban).

In a newer study earlier this month in the Journal of Medical Economics, University of Utah researchers working with Genelex, showed that the company's YouScript analysis cut ER visits by almost three quarters and reduced hospitalizations by more than one third in a retrospective registry cohort of elderly patients taking multiple medications.

Similar efforts are also underway in the context of PGx testing for drugs used in psychiatric treatment.

In some ways, psychiatric PGx testing has been welcomed more warmly by payors than drug response testing in other clinical contexts. Medicare contractor Palmetto in late 2014 finalized its local coverage determination under which Assurex Health's GeneSight Psychotropic pharmacogenomic test is covered under Medicare for major depressive disorder patients who have failed to respond to at least one neuropsychiatric drug.

But despite the relative hurdles for PGx in the cardiovascular space — no combinatorial PGx testing is currently covered by Medicare for cardiovascular drugs the way Assurex's psychiatric test is for psychotropic prescribing, and payors remain skeptical even with new clinical utility data being collected — Mikhail said that GnomeDx believes it is the right time to launch and is optimistic about the future.

According to the company, some private payors are reimbursing for its tests depending on their coverage policies. Meanwhile, some patients are opting to pay out of pocket if that makes the most sense for them.

In addition, GnomeDx offers zero-interest payment plans and financial assistance programs if patients are eligible.

Down the line, Mikhail said, the path for tests like GnomeDx's may not end up being a traditional payor-reimbursed path, but instead one where testing is adopted directly by healthcare providers and accountable care organizations that may recognize the value of such tests in reducing costs and improving outcomes in a context where such things are more directly valued.

"I think what is happening with the accountable care act … we are talking about capitated payments to show outcomes, performance-based medicine, and I think when everything settles, they will be the drivers of personalized medicine," he explained.

He added, "$136 billion a year, depending on whose numbers you believe, are wasted either on adverse responses or drugs that don't work. So why aren't we doing this?"

Mikhail would not detail what GnomeDx's testing volume has been in its first months of early operations, but he said it has not been as much as the company would like. And though discussions the company is having with major healthcare systems are "enormous," the actual culmination into testing a larger number of patients has yet to come.

"We are patient," Mikhail said," because we know that this is important and that it's coming."

GnomeDx is not alone in setting out to offer lab-based comprehensive PGx testing. Genelex has been operating for several years, and there have been several more recent newcomers to the field, including Kailos, which offers a low-cost service that allows patients to seek out testing, although not to actually receive results, without consulting a physician.

Admera Health (formerly GeneWiz) has been marketing its PGxOne test since 2014. Mayo Clinic also spun out a commercial company in 2014 called Oneome, which aims to provide accessible PGx analysis of existing genomic data from things like tumor sequencing or other prior genomic assays.

Mikhail said that GnomeDx believes its offering will be competitive, but in reality, he said, "there is plenty of room for plenty of people to provide [these] tests."

"I will be happier if we are a leading company in 10 years when we talk again, but I will be equally happy to see most people being tested by any means," he said.