Researchers at Medco and Mayo Clinic hope that a recently disclosed alliance to jointly evaluate the clinical and economic value of incorporating genetic testing into warfarin therapy may ease payor anxiety about using such information to make drug-coverage and reimbursement decisions.
The collaboration is the latest example of how disparate components of the healthcare system are studying the economics of pharmacogenomics, a missing metric that the industry widely believes has been retarding the adoption of these technologies.
The Medco/Mayo study follows on the heels of a similar study with warfarin by Harvard-Partners Center for Genetics and Genomics [see Pharmacogenomics Reporter 11-15-06].
The Medco/Mayo 1,000-patient, year-long study will begin enrolling in January 2007 and will focus on the CYP 2C9 and VKORC1 genes. Mayo will perform all the tests and interpret their results to help guide physicians as they consider warfarin dose adjustments for their patients.
The CYP 2C9 portion of the test will be performed using the Tm Bioscience Tag-It mutation-detection kit. VKORC1, meantime, will be assayed by PCR amplification using an in-house primer followed by direct sequencing of the amplification. “If Tm Bioscience introduces a kit for VKORC1, we will likely switch to that technology if the results correlate with direct sequencing,” Thomas Moyer, external affairs chairman of Mayo’s Department of Laboratory Medicine and Pathology, told Pharmacogenomics Reporter this week.
Medco, the second-largest pharmacy benefits manager in the US with 60 million beneficiaries, will gather the drug and hospital utilization data for the enrollees in the study.
“Mayo and Medco will pull the data together to determine whether doing this genetic testing reduced patient utilization of medical services,” Moyer said. The study results are expected to be released at the start of 2008.
Warfarin dosing can be tricky, since not enough drug can lead to unwanted clotting while too much can trigger a hemorrhage in patients. There are sparse guidelines regarding warfarin dosing, leaving physicians to titrate doses up or down until they reach a safe and beneficial response. This trial-and-error method, however, can be unsafe for patients and costly to the payors footing the bill.
“Our hypothesis is that most of these patients who have bleeding episodes will be identified by this genetic test,” Moyer said. “If physicians treat them in a slightly different way those patients will experience fewer bleeding episodes and therefore use fewer healthcare services in their followup treatment.”
News of the collaboration followed a presentation by J. Russell Teagarden, vice president of clinical practices and therapeutics at Medco, at a Harvard-Partners Center for Genetic and Genomics conference on personalized medicine in Boston last week. At the conference, Teagarden said while payors are interested in genetics, they need to see the “value proposition” of incorporating such data into coverage decisions in order to become comfortable with the concept.
“There are probably some people a little bit uneasy about just throwing [genetics] in. Well, we’re not going to just throw it in. We’re going to need more information first” about the predictive power and clinical significance of genetic tests, as well as about the penetration between genotypes and the prevalence of biomarkers in a given population, Teagarden said.
“We have a lot of associations [between genetics and outcomes] now but the clinical significance has yet to be determined,” he added. “We are finding a lot of interest in the payor community … but we need to show them the value proposition.”
Medco and Mayo expect the warfarin study to do just that.
This observational study will be implemented in typical community practice settings during a patient's normal course of treatment. Investigators will need to enroll at least 1,000 patients to reach statistical significance. Medco oversees approximately 200,000 new patients who start warfarin therapy each year. Eligible patients within this large pool will be invited to participate in the trial.
Medco estimates that approximately 2 million people in the US begin warfarin therapy each year to prevent blood clots. Due to the prevalence of warfarin use in the US, findings from the study could “have dramatic implications” for the PBM, Medco Chief Medical Officer Robert Epstein told Pharmacogenomics Reporter.
Teagarden noted that genetic testing can be used to facilitate a formulary exclusions process, which can make PBMs more efficient.
“If you know there is a small portion of the population that has a certain type of genotype that indicates that that is different for that small population then you can build it into your exceptions processes,” he explained. “If you build that exceptions process ... into your formulary for the masses, it will allow us to be more efficient with formulary design.”
“There are probably some people a little bit uneasy about just throwing [genetics] in. Well, we’re not just going to throw it in. We’re going to need more information first.”
Medco already uses genetic data to determine how patients with hepatitis C treated with interferons should be covered. For example, coverage duration depends on the viral genotype: Genotype 1 patients receive 12 months of coverage while genotype 2 and 3 patients are covered for six months.
The warfarin study is the first in a series of collaborations the partners plan in a range of therapeutic areas. Epstein envisions future partnerships investigating liver enzyme metabolism, among others.
Other PBMs have also gotten involved in gauging the value of incorporating molecular diagnostics in reimbursement decisions. Clinical Data recently aligned itself with PharmaCare – the fourth-largest PBM in the US covering more than 30 million members – to identify patients at risk for being improperly dosed for warfarin or for developing a potentially fatal adverse event when on clozapine, a schizophrenia drug. PharmaCare will use Clinical Data’s homebrew molecular diagnostics [see PGx Reporter 09-20-06].
The growing interest on the part of PBMs in personalized medicine is particularly meaningful since they process millions of prescriptions through large payors, and are important conduits to the healthcare reimbursement process. For their part, pharmaceutical companies are especially eager to ensure that their targeted treatments are covered and want to remain abreast of the kinds of methods that factor into a payor’s reimbursement decision making.
However, although there is “an appetite” for incorporating genetics into formulary processes, payors will only bite if there is credible data and regulatory backing from the FDA to do so.
“I would say labeling of the drug that references the importance, if not the requirement, of the test will be important, [as well as] some sort of credible guidelines from a credible institution that says this should be the standard practice,” Teagarden said. “A combination of the two would be very powerful.”
He added that while different payors will require different degrees of evidence, “something short of labeling and credible guidelines will have a low probability” of being covered.
In November 2005 the FDA Clinical Pharmacology Subcommittee of Pharmaceutical Science Advisory Committee recommended testing for variations in the CYP2C9 and VKORC1 genes in patients requiring warfarin therapy.
Additionally, during the most recent meeting of the Clinical Pharmacology Subcommittee on incorporating genetic information in tamoxifen’s label, Lawrence Lesko, director of the Office of Clinical Pharmacology and Biopharmaceutics, said the agency is in the final stages of negotiating the language to include genetic information in warfarin’s label [see PGx Reporter 11-15-06].
Last week, Pfizer said labeling for its investigational HIV drug Maraviroc may require patients to establish their CCR-5 tropism status before being prescribed the drug (see related story).
The FDA has so far relied on genotypic data to modify doses for patients using the acute lymphatic leukemia drug 6-mercaptopurine and Pfizer’s colorectal cancer agent Camptosar.