With Pradaxa On The Rise, Medco Gathers Evidence On Warfarin Diagnostic Testing

Pharmacy benefits management company Medco Health Solutions Inc. says that with the newly approved oral anticoagulant Pradaxa (dabigatran) off to a good commercial start, it plans to monitor outcomes and compare results with generic warfarin that has been optimized according to genetic testing.

A commercial battle has been looming between warfarin, which is cheap but cumbersome to use, and a wave of novel oral anticoagulants eager to steal its sizeable market share (Also see "Oral Anticoagulants Market Snapshot: Big Bucks, But Payers Are On Guard" - Pink Sheet, 25 Oct, 2010.). First out of the gate was Boehringer Ingelheim GMBH’s Pradaxa, approved by FDA in October 2010 for stroke prevention in patients with atrial fibrillation, and with labeling reflecting superior efficacy over warfarin. The wholesale price for the standard, higher 150 mg dose of Pradaxa is about $6.70 a day, exponentially more than generic warfarin.

Uptake of Pradaxa has been rapid, observed Felix Frueh, president of the Medco Research Institute, during a recent briefing at the headquarters of Medco subsidiary DNA Direct in San Francisco. Pradaxa has status as a preferred brand (Tier 2) on Medco formularies.

Decision Resources subsidiary Fingertip Formulary reports that the drug’s launch has been impressive. In the first four months on the market, the drug had preferred status for one-third of covered lives in the U.S., including commercial and Medicare plans. That compares favorably to the recent launches of other drugs in the cardiology space, according to Fingertip. To achieve that same level of coverage, it took from five to six months for Eli Lilly & Co,/Daiichi Sankyo Co. Ltd.’s anti-platelet therapy Effient (prasugrel) and six to seven months for Sanofi Aventis SA’s anti-arrhythmic Multaq (dronedarone), Fingertip reports.

The prescription data substantiate Pradaxa's growing market share. Scripts for Pradaxa rose from 20,000 in November 2010 to 52,000 in December and 76,000 in January, according to IMS Health. That compares to 2,686,000, 2,753,000 and 2,614,000 for warfarin in November, December and January, respectively.

It's still an uphill battle. Warfarin's total scripts for 2010 were 32,019,000.

Physicians may be swayed by the convenience of an oral anticoagulant. A recent survey by IN VIVO, a sister publication of "The Pink Sheet," and the Gerson Lehman Group, suggested physicians were actively prescribing Pradaxa for new patients and also switching from warfarin (Also see "The Power Of Pradaxa: Physicians Weigh In" - In Vivo, 1 Dec, 2010.). While efficacy and safety were rated as important criteria for prescribing the new drug, the most important factor was reduced need for monitoring dosing.

In a development that could spur further adoption, on Feb. 15, the drug was officially recommended as an alternative to warfarin for anticoagulation in non-valvular atrial fibrillation in new guidelines set jointly by the American Heart Association, the American College of Cardiology and the Heart Rhythm Society.

Medco is ready to collect observational data on the benefit of Pradaxa against warfarin, optimized by using genetic testing. The data will show which treatment is actually the better strategy for patients, executives say.

“What we don’t know and what we [will be] experiencing over the next few years is what is the real background of adverse events associated with this new therapy?" Frueh noted. "What we really have to do is compare optimized warfarin therapy with this new drug.”

Though novel anticoagulants will cost a lot more than warfarin, they also promise to save money in warfarin-related adverse events and monitoring of dosing. Medco has published a major study showing that genotyping patients can improve the safety and effectiveness of warfarin through more precise dosing and avoidance of costly hospitalizations (Also see "Raising The Bar For Anticoagulants? Warfarin Genotype Results Announced" - Pink Sheet, 22 Mar, 2010.).

Two genes have been shown to account for about 33% of variance in warfarin dosing: cytochrome P450 2C9 (CYP2C9) and VKORC1.

About 10 million out of 65 million Medco-covered lives have easy access, including reimbursement, for genetic testing.

Iverson Genetic Diagnostics, Inc., which markets a diagnostic gene test for warfarin, has its own study under way now to prove the value of genetic testing (Also see "CMS-Blessed Warfarin Genetic Testing Trial Aimed At Winning Over Payers and Docs" - Pink Sheet, 2 Mar, 2011.). The 18-month, randomized controlled WARFARIN trial will test 7,000 patients over the age of 65. The study has been authorized by the Centers for Medicare & Medicaid Services. Iverson believes that the more direct endpoints of severe bleeding and clotting adverse events will have more sway with payers and physicians than the hospitalization data generated by Medco.

Making The Case For Genetic Testing

Better use and performance of generics through guidance from genetic testing could theoretically translate into big cost savings for insurers, yet reimbursement for diagnostics remains low.

Medco has been encouraging use of genetic testing through studies and support services. The PBM provides pharmacy services to a range of clients including employers, labor unions, health plans, government agencies and Medicare Part D plans. Overall, its clients cover some 65 million lives in the U.S.

Since 2008, about 300 clients have signed on to offer coverage for certain genetic tests – now for six drugs – through the company’s personalized medicine programs. That translates into about 10 million patients, about one-sixth of Medco’s total number of members, who now have access.

A range of factors, including lack of reimbursement and awareness among professionals, has held back use of genetic testing. In a 2008 survey of 10,000 physicians by Medco and the American Medical Association, 98% responded that genetic profiles could influence drug therapy but only 10% said they were adequately informed about pharmacogenomic testing.

Medco acquired DNA Direct early last year as a means of providing decision support services for payers, providers and patients to help ensure appropriate use of genetic and molecular diagnostic tests (Also see "Medco Buys DNA Direct To Bolster Its Personalized Medicine Business" - Pink Sheet, 2 Feb, 2010.).

In addition to warfarin testing, Medco’s personalized medicine programs cover CYP2DG testing for tamoxifen scripts. Tamoxifen is active as a pro-drug and some women have trouble metabolizing the breast cancer therapy, resulting in much higher rates of recurrence.

Under Medco's programs, if an order for a particular drug comes into a pharmacy, the medicine is dispensed but prescribing doctors are also automatically alerted that pharmacogenomic testing is available and covered by insurance. Medco helps coordinate the collection of DNA samples from patients and their shipment to a qualified laboratory, and communication of test results to physicians.

Strong Support Spurs Use

Providing strong support for testing boosts use, according to a Medco Research Institute study presented at the American Society of Human Genetics annual meeting in Washington, D.C. in November 2010. In particular, the study looked at CYP2C9/VKORC1 testing to guide dosing of warfarin and CYP2D6 testing for response to tamoxifen.

The Medco team says it was able to increase the rate of warfarin genetic testing 45-fold, with 15% of eligible patients obtaining a test compared to the usual benchmark rate within the Medco system of just 0.34%. As for tamoxifen, the typical rate of testing is 3.6%, but for the patients with insurance coverage and the support system it was seven times higher at 24%.

In addition to tamoxifen and warfarin, Medco has also been targeting genetic testing of Bristol-Myers Squibb/Sanofi Aventis' Plavix (clopidogrel) to identify responders. Patients with genetic differences in CYP2C19 alleles have a hard time metabolizing clopidogrel and receiving the drug effect. The drug now carries a "black box" warning to this effect.

With Plavix going off patent in 2011, Medco has pointed out there could be significant cost savings for plans in optimizing treatment and argues that when genetic response is factored into the equation, efficacy is competitive with newer branded drugs, notably Effient.

However, some cardiologists have questioned the role of genetic testing in anti-platelet therapy (Also see "Debate On Antiplatelet Gene Testing Continues; First Point-Of-Care PMA Filed" - Medtech Insight, 6 Sep, 2010.). And the large GRAVITAS study failed to show the value of platelet function testing and dose adjustment in patients who have had percutaneous coronary interventions .

Medco is sponsoring the Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study or GeCCO comparing the two drugs in almost 15,000 patients who are able to metabolize Plavix. Results could become available later this year.

At the moment, insurers are still very reluctant to cover genetic testing outside the universe of Medco’s personalized medicine programs, DNA Direct CEO Ryan Phelan observed at the San Francisco briefing. Some research indicates that health plans don’t see the pay-off for such testing (Also see "Personalized Medicine Pay Off For Pharma, Payers Contrasted In Study" - Pink Sheet, 23 Feb, 2009.).

Even when randomized trials show a benefit, health plans may have doubts about how the tests perform in the real world.

Even when randomized trials show a benefit, health plans may have doubts about how the tests perform in the real world, for example, whether physicians will actually act on genetic test results. Studies are needed to show how many times recommendations of a test are followed in routine practice, Frueh said.

“For payers, that is the ultimate hurdle, they want to know what they are paying for,” Frueh said.

By Emily Hayes