CLOPIDOGREL A second-generation thienopyridine antiplatelet agent, an - PowerPoint PPT Presentation

P he hen G en ene P 2 Y 12 12 T es est 1

CLOPIDOGREL A second-generation thienopyridine antiplatelet agent, an antagonist of platelet P2Y 12 receptor • Inhibits the formation of blood clots in the coronary, peripheral & cerebrovascular arteries • METABOLISM AND ACTION OF CLOPIDOGREL 2

Problem – limited effectiveness of clopidogrel Pharmacodynamic evidence recognized by the FDA, American College of Cardiology, American Heart Association, and European Society of Cardiology suggests that clopidogrel has a suboptimal effect in a substantial proportion (“about one third”) of patients and that increasing the dose has limited efficacy in selected patients. Clopidogrel is not effective in about 1/3 of individuals One of the most prevalent reasons for reduced response to CLOPIDOGREL is inefficient conversion of the drug into its active metabolite due to genetic variability in liver enzymes 3

No easy-to-use test for clopidogrel effectiveness Clopidogrel effectiveness is not routinely measured due to current assessment of platelet function requiring testing within a • limited time of taking the blood sample specialised equipment and technical expertise requirements on site • • Ineffective treatment can increase the risk of a recurrent cardiac event or stroke • Overly effective treatment can lead to excessive bleeding 4

Our Solution To identify patients who are not responding to Clopidogrel using P he hen G en ene P2Y 12 12 Te Test that includes: Genotyping: CYP2C19 enzyme • o Involved in the metabolism of clopidogrel o Every individual has two CYP2C19 alleles o Depending on the combination of alleles in an individual, drug- metabolizing phenotypes associated with the CYP2C19 enzyme can vary Phenotyping: assessing platelet reactivity in response to stimulation with • agonists High on-treatment platelet reactivity correlates with recurrent o thrombotic events Blood samples are collected, processed using simple kit and are sent for analysis at a central laboratory – no need for specialised equipment on site and no time limitations to perform the analysis 5

Supporting Studies 6

Importance of CYP2C19 Genotyping In 2009, the US Food and Drug Administration (FDA) issued a boxed warning, recommending “consideration of CYP2C19 genotype” prior to prescribing clopidogrel. 7

OUR WORKFLOW Assess anywhere Sample Collection Sample Shipment Sample analysed Electronic reporting & Processing Patient on antiplatelet Blood sample taken and Processed sample is Laboratory staff analyse Complete test results are therapy can be assessed processed using simple, shipped to a central sample for P-selectin reported back in primary care or home drug-specific kit processing lab in the UK using flow cytometry electronically setting and CYP2C19 using Luminex Platform 8

Advantages of this combined testing • Identify at risk patients with sub-optimal response to Clopidogrel using both genotyping and phenotyping approaches • Results allow healthcare providers tailor the prescription of antiplatelet agents for their patients accordingly to reduce the risk of myocardial infarction, stent thrombosis or stroke • No capital investment is required on site to setup the testing – all that is needed is an easy-to-use testing kit to process and stabilise the blood sample, which is then sent for expert analysis to a central laboratory