The US Food and Drug Administration this week said it plans to use patient databases held by pharmacy-benefit manager Medco to help it assess the pharmacogenomic safety and efficacy of currently marketed and investigational drugs, and to determine which drug labels should be updated to include genetic risk information.
“A goal of this collaborative research is to identify drugs currently approved, or drugs to be approved in the future, for which pharmacogenomics may improve the dosing, effectiveness, or safety,” Lawrence Lesko, director of FDA’s Office of Clinical Pharmacology, told Pharmacogenomics Reporter this week.
Medco, the second-largest PBM in the US with 60 million beneficiaries, said in a statement it will "supply a large portion of the data to be used in the reports for the FDA." For its pharmacogenomic studies and labeling updates, the FDA will plumb Medco’s claims database for prescription volume, prescription patterns, and treatment outcomes in its studies of marketed drugs.
Although the exact nature of Medco’s reports to the FDA will not be determined until the FDA begins its studies, Lesko said he imagined that the reports could possibly “identify specific drugs with links to outcomes for which genetic factors may play a role,” and offer insight into “what barriers exist to physician and patient acceptance of genetic testing and what their attitudes are.”
According to a Medco spokesperson, the first projects under the collaboration will be determined in the fall. The agreement runs through the end of August 2010.
“Initially, we'll be looking at drugs like [warfarin] and tamoxifen, and any new tests that may come to market during the course of our collaboration,’’ the Medco spokesperson told Pharmacogenomics Reporter.
According to Lesko, the collaboration will be supported by FDA’s Critical Path funds, since one of its main aims is to "assess drug safety using new tools, including pharmacogenomics."
Financial details of the collaboration were not disclosed.
More Labeling Changes?
With its large claims database and connections to the patient community, Medco will also provide data to the FDA that could be used to add genetic risk information to the label of certain drugs.
“We will also be interested in the adoption of genetic tests by physicians and patients for those drugs that FDA specifically re-labeled with genetic information, including warfarin, and also drugs which are candidates for re-labeling with genetic information, such as tamoxifen,” Lesko said.
In December 2006, eight months before the FDA updated warfarin’s label to include genetic risk information, Medco partnered with the Mayo Clinic to study the clinical and economic utility of using molecular diagnostics to help physicians dose the popular anticoagulant [see PGx Reporter 12-06-2006].
FDA’s collaboration with Medco might move the agency to update warfarin’s label again with the type of information payors need to start covering genetic tests.
Despite the FDA’s update to the warfarin label with genetic risk information and the FDA’s clearance of several genetic tests for the indication, many insurers have not covered the test, and doctors have been slow to adopt PGx-based warfarin dosing, citing the lack of clinical utility data. Meanwhile, diagnostics developers have criticized the FDA for failing to highlight the importance of pharmacogenomic-based warfarin dosing in its labeling update.
FDA’s collaboration with Medco might move the agency to update warfarin’s label again with the type of information payors need to start covering such genetic tests. According to Lesko, the FDA will be looking at Medco’s databases for whether CYP2C9/VKORC1 testing for warfarin improves outcomes.
“FDA is … interested in collecting data on what doses are most appropriate for specific genotypes of warfarin, and if there are significant differences in clinical outcomes between patients genotyped and patients not genotyped,” Lesko said.
The agency will use this data, along with other published data and its in-house simulations, to decide whether to use this data to update warfarin’s label with genotype-specific dosing information, he added.
The FDA will also be looking at Medco’s experience with CYP2D6 testing to determine whether PGx-based tamoxifen administration improves outcomes.
Medco announced in October that it was working with the Laboratory Corporation of America to determine if Roche’s AmpliChip can improve dosing for the breast cancer drug [see PGx Reporter 10-31-2007].
This fits nicely with the FDA’s plans to update tamoxifen’s label with information about genetic tests that can identify women not likely to respond to the drug. In October 2006, an FDA advisory committee recommended that the agency ask drug makers to update the label for the breast cancer drug to include information about CYP2D6 genotype testing [see PGx Reporter 11-15-2006].
“FDA expects to use the data from this collaboration in the same way it uses any post-marketing surveillance data,” Lesko noted. “This research is targeted specifically to genomic opportunities to improve the ways drugs are used.”
While the data gleaned from the Medco collaborations could be used to update drug labels with genetic information or include more specific genetic data in drugs already re-labeled, “these data will not result in making go/no go decisions for investigational drugs or for regulatory decisions on New Drug Applications,” Lesko stressed.
The partnership between FDA and Medco was inked after the agency published a solicitation in May in the Federal Register. Medco and several other firms responded to the announcement.
However, the agency felt that Medco, a PBM that processes 500 million prescriptions annually and has organized its own personalized medicine initiatives, “was well positioned to have access to the information that would achieve the goals of the collaborations,” Lesko said.
“Medco and FDA will collaborate on developing … strategies for advancing personalized medicine and pharmacogenomics,” he said. “Both contribute intellectual capital since both organizations have the scientific and clinical expertise in this area.”
The Medco spokesperson added that Medco with its claims data hopes to help the FDA enhance its expertise in using pharmacogenomics to improve the efficacy and safety of drugs.
“The FDA knows the pipeline for these tests and they know a lot about pharmacogenomics. What they are looking for is a better understanding of the real-world application of a test or a potential test, and that is what Medco will provide,” the spokesperson said.
However, a successful collaboration is also contingent on the like-mindedness of the people involved. In this case, the FDA may be working with one of its own, Felix Frueh, who recently left the agency to head up Medco’s pharmacogenomics divisions.
Around the same time the FDA put out the solicitation for a partner, Medco announced that it had snagged Frueh from the FDA to be VP of personalized medicine R&D, and to develop and manage Medco’s Personalized Medicine Research Center, in Whitestown, Ind.
Prior to joining Medco, Frueh was associate director for genomics at the US Food and Drug Administration’s Office of Clinical Pharmacology in the Center for Drug Evaluation and Research. He also was chair of the FDA’s Interdisciplinary Pharmacogenomics Review Group.
Medco would not say to what extend Frueh would be involved in the collaboration. “Medco is still determining staffing for this project,” the Medco spokesperson said.