Personalized Medicine at Medco

In a recent press release, Medco Health Solutions announced that it is partnering with the FDA to study the applicability of personalized medicine methodologies to prescription drug treatment. Medco is the nation’s leading pharmacy benefit manager and the announcement signals the continued mainstreaming of pharmacogenomics in healthcare.

Medco and the FDA will jointly develop research projects, programs and strategies in the area of pharmacogenomics, the science of using a patient’s genotype to predict their response to drug treatments.

Medco’s objective is to advance pharmacy care and take some of the guesswork out of the prescription process. Specifically, the objectives of the program are to address:

Safety of prescription drugs
Physician participation in pharmacogenomic testing
Usefulness of tests in prescribing
Quantifying prescription information about drugs

Central to the research studies will be Medco’s extensive database of pharmacy claims. Medco is already involved with pharmacogenomic studies including Warfarin at the Mayo Clinic and tamoxifen with LabCorp.

Personalized Medicine to the Rescue

The story of pharmacogenomics has reached the mass media, a.k.a. the Wall Street Journal, as a means of stemming the tide of failed drug candidates beleaguering the pharma industry. The article cites drugs from Novartis AG, NitroMed, and Clinical Data that have saved drugs that had, or would have, failed to make it to market by targeting patient sub-groups based on genotype.

Of significance in the article is stating that the pharmaceutical blockbuster model is dead and that personalized medicine may represent the new paradigm. There are in fact upsides to the smaller markets that personalized medicines command, i.e. high switching costs. With a "one-size-fits-all" drug a patient can move from one medication to another with just a trip to the pharmacy, but when using a drug is customized to a patient’s genotype, switching to a drug that is known to be less effective will be a non-starter.

One local Colorado play that illustrates the resurrection of a "failed" drug is the in-licensing of bucindolol by ARCA Discovery. Although an earlier Phase III clinical trial of the drug was terminated due to lack of efficacy, evidence has shown that certain patient sub-groups that exhibit specific genetic polymorphisms can benefit from the use of the drug.

Although the NIH Roadmap Initiatives that promoted personalized medicine and biomarker approaches four years ago weren’t mentioned in the article, the cause has been taken up by the pharmas as a new way to fill those emptying drug pipelines.

AutoGenomics' Warfarin Panel

GenomicWeb News (sub required) reported on Harvard-Partners Center for Genetics and Genomics' completion of an evaluation of AutoGenomics' Infiniti 2C9-VKORC1 assay; a genetic test to determine correct dosing for warfarin. This announcement has come on the heels of the FDA's approval of new labeling for warfarin suggesting that an individual's response to the drug is dependent upon their genetic makeup.

HPCGG is participating in a clinical trial entitled: Creating an Optimal Warfarin Nomogram Trial (CROWN) to incorporate both clinical and genetic information in determining the correct warfarin dosing.

FDA Steps into Personalized Medicine

Last week the FDA approved new labeling on the blood thinner Coumadin and its generic form, warfarin. The new labeling suggests that an individual's response to the drug is dependent upon their genetic makeup. Not only is the FDA opening the door to personalized medicine, but they are actually taking a leadership role in doing so, a role not characteristic of the agency.

Warfarin has been in use for some 50 years during which time it was evident that individual response to the drug was widely varied. Dosing requires careful monitoring of patients who could suffer life-threatening bleeding if dosages were too high and life-threatening clotting if the dosage were too low. A number of factors such as patient size, age and other medications were attributed to the variability in results but it was obvious that these factors did not explain the entire story.

A story in the WSJ (sub required) last week pointed out that studies over the past decade have identified two genes that were tied to the variance in results: CYP2C9 and VKORC1. Variants in either or both genes lead to different drug responses in individuals. Combining size, age and an individual's genotype can increase the confidence with which a doctor can prescribe a patient's dosage.

The FDA's leadership in making this move is a direct result of its Critical Path Initiative, a broad initiative undertaken by the agency to modernize biomedical sciences with the goal of improving the nation's healthcare. A cornerstone the CRI is the improvement of evaluation tools, specifically biomarkers and disease models. By taking this step the FDA is actively encouraging the use of pharmacogenomics; the use of genetic markers to predict an individual's response to a drug.

Already a number of labs have begun offering genetic tests for CYP2C9 and VKORC1 such as the Mayo Clinic and Labcorp. Osmetech announced last Friday that they are developing a warfarin assay that they plan to have available by the first half of 2008.

This is all being done without a critical clinical trial; the trial that compares a group of patients that are treated without genetic testing against a group that are treated with genetic testing. Given the fact that the health risk to patients without genetic testing is reduced by the extensive monitoring they undergo during their initial dosing, it is questionable whether the genetically tested patients will actually have a lower health risk. However, by taking some of the guess work out of the dosage process, doctors can more quickly converge on the correct dosage, reducing the time the patient must spend in an over- or underdosed state and certainly cutting down on visits to the doctor for monitoring.

ARCA Discovery and LabCorp

Early stage PGx company ARCA Discovery and mega-lab LabCorp have announced a deal to develop and commercialize a genetic test to aid in prescribing bucindolol, a drug now under development at ARCA. As a pharmacogenomic drug, bucindolol will be prescribed only to a select patient sub-group who have shown a benefit from using the drug. Although bucindolol has yet to receive FDA approval, such an approval will be contingent upon both the efficacy of the drug in the selected patient sub-group and the ability of the diagnostic test to select those patients. Bucindolol has already undergone extensive phase III trails where was shown to be ineffective over an unfiltered patient population. However, in a subsequent substudy it was shown that patients with certain genetic variations showed significant improvement on the drug.

It's interesting to see the progression of this idea from the universities where it was first discovered, to a start-up company where its commercial potential was analyzed and promoted and now to a large diagnostic company where its commercial potential will (hopefully) be realized. It is a classic example of technology transfer and how it can be done.