By Turna Ray
As part of its Genetics for Generics program, Medco is planning a comparative effectiveness study of two competing blood-thinning drugs • Bristol-Myers Squibb's soon-to-be off-patent Plavix and Eli Lilly's newer, more expensive Effient • to assess whether it will be clinically useful and cost-effective to genetically test Plavix patients to establish their CYP2C19 status.
Genetics for Generics is a newly launched Medco project for optimizing savings for payors by dispensing off-patent drugs with the aid of genetic tests. According to Medco's Chief Medical Officer Robert Epstein, the goal of the Genetics for Generics program is to "beef up the profile of a generic drug and make it even smarter" [see PGx Reporter 10-07-2009].
Medco's study will examine whether the 70 to 75 percent of patients who are "extensive metabolizers" of Plavix will have "comparable outcomes" with patients taking Effient. Manufactured by Eli-Lilly and Daiichi Sankyo, Effient was approved by the US Food and Drug Administration in July and is indicated as a treatment to reduce the risk of blood clots in patients who undergo angioplasty.
"In this particular case, because Plavix will go generic in two years, should the study show that the effectiveness of Plavix for extensive metabolizers is comparable to that of Effient, we can provide patients and physicians with a choice of being able to stay on the lower cost generic drug," Felix Frueh, Medco's vice president of research and development in personalized medicine, told Pharmacogenomics Reporter.
According to reports, Eli Lilly and Daiichi Sankyo have priced Effient at an 18 percent premium to Plavix.
Frueh noted that the "is an excellent example of Medco's Genetics for Generics strategy, aiming at maintaining the same quality of care at a lower cost."
In a 13,608-patient trial comparing Effient (prasugrel) to Plavix (clopidogrel), fewer patients on the Effient arm experienced non-fatal heart attacks than in the Plavix arm. However, patients on Effient with a history of stroke were more likely to have another stroke in the study. Additionally, the study found that while Effient showed greater efficacy than Plavix, those on the newer drug displayed a higher risk of fatal bleeding.
"Prasugrel has shown greater efficacy but higher bleeding risk than clopidogrel in head-to-head clinical trials, but to date none of the studies limited the patient population to those who extensively metabolize clopidogrel, which could substantially impact the results," Medco said in a statement this week. "The study could have important patient safety ramifications and significant cost implications for health plans that pay for these drugs."
Plavix, Bristol-Myers Squibb's best-selling product, with worldwide net sales of $1.5 billion last year, is a perfect candidate for Medco's Genetics for Generics program since it is going off-patent in November 2011. Furthermore, the labeling for BMS/Sanofi-Aventis' Plavix was recently updated by the US Food and Drug Administration to inform doctors and patients that poor CYP2C19 metabolizers have diminished response to the drug and increased risk of heart attack [see PGx Reporter 06-17-2009].
Studies like the one being conducted by Medco are "necessary to show how innovation can derive greater value from what we spend on health care," Michael Leavitt, former HHS secretary and a personalized medicine advocate, said in a statement. "What we learn from this study, and others like it, will save lives and money."
The Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study will enroll more than 14,000 acute coronary syndrome patients who have been newly prescribed either Effient or Plavix, and compare the efficacy of these drugs by measuring the rate of cardiovascular deaths, nonfatal heart attacks, and nonfatal strokes. Patients will be followed for six months.
Medco will enroll patients for this study beginning late fall and ending mid-2011. The results of the study will be released in 2012. Patients in the clopidogrel arm of the study will be required to give a saliva sample so their CYP2C19 status can be established through genetic testing. Genomic analysis will not be conducted in the Effient arm, since the drug is metabolized through a different pathway.
"This study could have a huge bearing on patient safety and the costs to treat this condition. Plavix is going generic in 2011 and if found to be equally effective as Effient for patients who have a normally functioning version of the CYP2C19 gene, the study provides the evidence that would allow these patients to opt for a lower cost treatment," Epstein said in a statement.
Comparative effectiveness research as a means to control healthcare costs by providing coverage for the most beneficial, cost-effective drugs is a strategy that has the backing of the Obama Administration and has received $1.1 billion in funding under the American Recovery and Reinvestment Act of 2009. Medco is not participating in federally funded comparative effectiveness research efforts and is conducting this study on its own.
Due to pending legislation and efforts in Congress to limit how comparative effectiveness data is applied to make insurance and reimbursement decisions, it is currently unclear the extent to which government and private payors will be able to apply CER. According to Medco's Frueh, the company is conducting such studies not to guide reimbursement decisions but to provide choice and encourage more informed decision-making in the healthcare system.
"The ultimate intent of this study is to determine which drug serves the intended-to-treat population best," Frueh told Pharmacogenomics Reporter. "Comparative effectiveness is about evaluating the clinical benefit and creating data that helps doctors and patients make better treatment decisions.
Medco's study comparing Effient and Plavix will also collect information on physician action taken based on genetic information and on how application of this information improves clinical outcomes in the 25 percent to 30 percent of patients who are poor metabolizers of Plavix due to their CYP2C19 genotype.
Medco is one of the largest pharmacy-benefit managers in the US representing 60 million people, and is actively employing personalized medicine strategies to reduce cost and improve treatment benefit for its members.
Medco's ongoing PGx studies for warfarin sensitivity and tamoxifen response will fall into the Genetics for Generics program, as will the recently penned collaboration with Celera to evaluate whether testing for the KIF6 gene variant increases patient adherence with statin therapy [see PGx Reporter 12-04-2006; 10-31-2007; 09-23-2009].