Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Reporter: Aviva Lev-Ari, PhD, RN

Moving Beyond Plavix PGx

Before it lost patent protection this year, clopidogrel was known under the brand name Plavix and marketed by Bristol-Myers Squibb. The Food and Drug Administration first updated the label for Plavix in 2009 to inform doctors that CYP2C19 poor metabolizers experienced diminished response to the drug and that PGx tests could be used to identify genotypes linked to variable treatment response. Then, in 2010, the FDA added a “black box” warning to Plavix’s label to highlight that poor metabolizers, or patients with the CYP2C19*2/*2 genotype, “exhibit higher cardiovascular event rates following acute coronary syndrome or percutaneous coronary intervention than patients with normal CYP2C19 function.” (PGx Reporter 3/17/2010)

Despite FDA’s vote of confidence in the association between certain CYP2C19 loss-of-function alleles and reduced response to Plavix, there is disagreement among healthcare providers about whether PGx testing in this setting is ready for broad implementation.

Scripps Health was an early adopter of PGx testing for Plavix. When in 2009, Scripps Health and Quest Diagnostics inked a deal to offer CYP2C19 testing to patients undergoing stent procedures, many doctors felt the program was premature given the evolving nature of the science (PGx Reporter 10/28/2009). The controversy has only gotten more contentious as several published meta-analyses have yielded conflicting results as to the validity of the association between genotype and drug response (PGx Reporter 3/28/2012).

The FDA has maintained that the available evidence supports its genetic testing recommendation for Plavix. In this regard, it is perhaps fitting that a forward-looking genetic testing program for Plavix is being launched at UF. Lawrence Lesko, former director of the Office of Clinical Pharmacology at FDA’s Center for Drug Evaluation and Research, who played a leadership role in adding PGx information to Plavix’s label, currently heads UF’s Center for Pharmacometrics and Systems Pharmacology and plays a leadership role in the university’s personalized medicine activities.

According to Johnson, UF launched its personalized medicine program with Plavix PGx testing because the black box warning on the drug’s label provided regulatory backing for implementing such testing. Additionally, “the things you potentially can impact with testing, such as major cardiovascular events, are clinically important,” she added. “We also felt that [since] the CYP2C19-clopidogrel effect is strongest in patients who are post percutaneous coronary interventions, that would allow us to focus on a very small patient population and a small number of physicians.”

Although UF’s genetic testing program is currently focused on cardiac patients who could potentially be treated with Plavix, the university has much bigger personalized medicine plans. “As we begin to roll out other pharmacogenomic indications [for cardiology patients] … we will also move past the cath lab … to the heart failure or electrophysiology clinic,” Johnson said, adding that the university intends to eventually implement genetic testing programs for gastroenterology patients.

“CYP2C19 testing for Plavix is just our starting point, so we can really work out the kinks, figure out how to educate the clinicians, figure out the barriers in a relatively confined setting,” she said. “But really, our goal is that we would run this chip on everybody presenting to the health system.”

http://www.genomeweb.com//node/1096991?hq_e=el&hq_m=1303351&hq_l=9&hq_v=e1df6f3681