A perennial question in pharmacogenomic circles is whether payors will pick up the tab for a new molecular diagnostic or exotic targeted therapeutic.
Now Clinical Data has signed a deal that could see a large national pharmacy benefits manager using its testing service to improve how two common drugs are prescribed.
The end result could enable the PBM, PharmaCare Management Services, to use Clinical Data’s SNP-based tests to gauge whether certain drugs in its formulary will trigger an adverse event that’s dangerous to the patient and costly to the payor. It could also open the door to a novel revenue stream for Clinical Data just as the company begins to roll out two homebrew tests.
“This is fairly new and fairly innovative, and I think it’s smart,” said Dana Felthouse, president of the Pharmacy Benefit Management Institute, a PBM research organization based in Scottsdale, Ariz. “There’s tremendous potential in pharmacogenomic diagnostics to improve patient safety” and ensure that “payors will not be investing in therapies that will not be beneficial to patients.”
The deal is also significant because large PBMs, which process millions of prescriptions through payors such as managed care groups, insurance companies, unions, and government agencies, are important waypoints in the healthcare reimbursement process. Because of this, pharmas eager to ensure that their targeted treatments are covered will want to keep track of the kinds of methods that factor into a payor’s reimbursement decision making.
Clinical Data has aligned itself with the fourth-largest PBM in the US. PharmaCare, a subsidiary of chain drug store giant CVS, covers more than 30 million employees and processes 13 million prescriptions each year through a network of more than 55,000 retail pharmacies nationwide.
Terms of the deal call for Clinical Data unit PGxHealth to use its molecular diagnostic services to help PharmaCare identify patients at risk for being improperly dosed for warfarin, the widely prescribed anticoagulant, or for developing a potentially fatal adverse event when on clozapine, a schizophrenia drug.
“The primary focus at the PBM level is a weighing of clinical and economic [factors],” Clinical Data CEO Drew Fromkin told Pharmacogenomics Reporter this week. “So they’re constantly looking at the risk-reward … equations in terms of what they can do less expensively while not negatively affecting how people [respond to] the drugs.”
The deal between PharmaCare and Clinical Data, which will go into effect when Clinical Data’s tests are launched later this year, is “a logical connection,” added Chip Phillips, chief operating officer for PharmaCare’s specialty services unit.
The Warfarin Dosing Challenge
In the case of warfarin, because the drug has a very narrow therapeutic window — not enough warfarin can lead to unwanted clotting while too much can trigger a hemorrhage — physicians are typically left to titrate doses up or down until they reach a safe and beneficial response.
But this method can be risky to the patient and costly to the payor footing the bill. In a typical case with PharmaCare, the PBM could, through its pharmacies, red-flag these prescriptions and intervene with Clinical Data’s molecular diagnostic option.
“In those instances, at the very least, there is a great opportunity for a PBM to [say], ‘This patient now changed her dose twice, which means they have exponentially increased their likelihood of having a negative event, and this is the perfect time for us to interject a genomic test for warfarin” to see if the patient is a high or low metabolizer, said Fromkin.
“There’s a great opportunity for the PBM to say, ‘Hey, you should get this test,’” he said.
Clinical Data’s warfarin test interrogates metabolism-related gene variants. Warfarin’s safety and efficacy profiles are well known and the FDA last November added pharmacogenomic-based drug-metabolism information to its label.
Asked whether the PBM will turn this information into a suggestion or a condition for prescription, Fromkin said it could go both ways. “It all depends on the kind of [health] plan” the individual has.
Theoretically, PBMs can use this kind of test for drugs with similarly narrow windows that are typically prescribed as maintenance therapies.
Clinical Data plans to launch the warfarin test “likely next month” and will perform the test in its CLIA labs.
Clozapine and Drug Choice
Clozapine became part of the deal because Clinical Data has been developing a test to identify individuals at risk for a potentially fatal disorder with the drug. This is important because schizophrenia patients often quit their treatments after experiencing adverse events or poor efficacy, which could put significant economic strains on payors.
It can take as many as five years and an average of four different therapies of essentially hit-and-miss means before patients with schizophrenia are prescribed a safe and efficacious drug. Many individuals, fed up with adverse events or poor efficacy, lose patience and quit before the right drug is found. Clozapine is a third-line schizophrenia treatment, according to the FDA.
Left unmanaged, these patients end up “in the hospital or in institutions and need help, and that’s multi-tens-of-thousands of dollars in healthcare costs beyond the drug they’re taking,” Fromkin said. In the end schizophrenia often becomes grueling for patients and costly to payors, who “pay the majority of the bill” because “many patients are on assistance,” Fromkin said.
In addition, clozapine could represent “a tremendous opportunity to reduce the [treatment] cost” because as a generic it is likely to be less expensive than comparable brands, and because “most people” who are prescribed clozapine don’t respond to the branded alternatives in the class, said Fromkin.
But the drug is associated with agranulocytosis, a potentially fatal disorder marked by an inability to create white blood cells. Because approximately 0.8 percent of individuals taking clozapine develop the condition, the FDA has required that patients prescribed the drug must have failed at least two other treatments, and must undergo regular blood testing to detect white blood-cell depletion.
PharmaCare’s Phillips said that “it makes you wonder if this [clozapine] test could give rise to the FDA loosening the requirement associated with all the subsequent blood work,” which are reimbursed by payors. He said this is “speculation and a goal.”
Clinical Data continues to expect to launch its clozapine test before the end of the year.
“There’s tremendous potential in pharmacogenomic diagnostics to improve patient safety” and ensure that “payors will not be investing in therapies that will not be beneficial to patients.”
Does the Doc Need to Be the Game?
The Clinical Data alliance initially will be limited to certain of PharmaCare’s businesses — the PBM is currently looking for sites to introduce the protocol — and it may decide to expand it if it likes what is sees, according to Fromkin.
But in both pilot drug cases the PBM will take advantage of the relationship its formulary has with prescribing physicians. Doctors and PBMs, through their pharmacy networks, communicate regularly, and PharmaCare would theoretically tell clinicians that a test exists that could help them find better warfarin thresholds, or suggest a test that would determine if a schizophrenic refractory to the first- and second-line treatments will develop agranulocytosis when prescribed the third.
After the physician draws blood for the test and sends the sample to Clinical Data, the company runs the test and produces its results along with a report suggesting steps the physician should take.
In the case of warfarin, “I would expect that while dosing algorithms have not been fully finalized, we probably give the physician the science behind what that kind of determination means to a dose,” Fromkin said.
In the case of clozapine the result will be a yes/no answer disclosing whether a patient carries a SNP that places him at high risk for agranulocytosis.
Fromkin said PharmaCare and Clinical Data want to work together “in other issues where we may have a class ruled by brands where there are really good generics, but, like clozapine, have been relegated because they’re just a bit older and have lost their sheen or maybe a piece of the population wasn’t getting efficacy, so let’s see if we can hone in on these markers and start to use some of these more efficacious and less expensive therapies again.’”
PharmaCare’s Phillips agreed, saying “it’s possible that generic makers of clozapine could potentially benefit from positive adoption of this test and its widespread use, whereas branded manufacturers of antipsychotics might not be so happy.”
However, he stressed that the alliance isn’t meant to “gut” branded drugs in favor of generics, “or vice-versa.”
“If I’m a pharma [company], I would certainly be monitoring the entire genomic space and those organizations involved in the identification of markers that might have an impact on the use of medications,” said Phillips.
The deal could also embolden other PBMs to strike similar diagnostic alliances and avoid having to rely exclusively on physicians’ use of emerging technologies — a dynamic that could open a new revenue stream for companies like Clinical Data.
Fromkin said that “adoption [of these technologies by PBMs] will begin to accelerate when we start to see these kinds of protocols get baked into [healthcare] plan designs … and when [plans] put protocols in place that flag it for docs that are not aware of the opportunity.”
Phillips added that “it’s difficult to predict when there will be adoption of these kinds of tests by clinicians for the purposes of making prescribing decisions. But I think we can all agree that though we can’t predict the timing it will get here inevitably.”