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McCormack Pharma Announces a Breakthrough Discovery in the Mechanism of Clopidogrel Resistance

LONDON, Nov. 3, 2014 /PRNewswire/ — A landmark discovery by McCormack Pharma provides a new insight into why some patient subgroups are at increased risk of showing resistance to the popular anti-platelet drug clopidogrel (Plavix). Importantly, these ground-breaking findings suggest that at-risk patients can easily be identified by an inexpensive assay; or for expediency, an alternative approach to individual screening may be the universal co-prescription of a currently-available safe and inexpensive prophylactic agent.

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In clinical practice, clopidogrel is a mainstay together with aspirin, in the management of patients with coronary artery disease, acute coronary syndromes, and in patients undergoing percutaneous coronary interventions. However, resistance to clopidogrel has been shown to be present in 25% to 30% of Caucasians and in an even higher percentage of Asians. Consequently, a significant proportion of patients remain at risk for subsequent death, myocardial infarction, stent thrombosis and stroke because of an insufficient anti-platelet effect.

Clopidogrel is a prodrug for an active thiol metabolite that is generated by the cytochrome P450 (CYP) enzyme system. Inadequate responses to clopidogrel may be caused by polymorphisms in one or more of the cytochrome P450 enzymes, notably CYP2C19. However, when the mechanisms of clopidogrel resistance are explored across studies, polymorphisms in the CYP2C19 gene only partially explain the correlation with suboptimal clopidogrel response.

Using proprietary relational databases, subsumed within their data mining platform known as CEME, McCormack Pharma provides new evidence for the existence of a previously-unknown pathway that has the power to bypass and surmount clopidogrel's blockade of the P2Y12 platelet receptor. In their report McCormack propose that upregulation of this pathway is controlled by a circulating marker that is typically elevated within discrete subpopulations of patients. Accordingly, clopidogrel will be less effective in those patients in whom this endogenous pathway is active especially within individuals who are known to carry a loss-of-function CYP2C19 allele. Attenuating levels of this circulating marker appears to be a straightforward solution in low-responding patients; but as McCormack emphasizes, this remains to be tested.

Further details on this discovery including release of the full report are available at

About clopidogrel

Historically, the patent-protected Plavix was a much-prescribed anti-platelet drug that as the second best-selling drug in the world achieved $9.4 billion in global sales in 2010. As a lifesaving drug of major significance, since its approval by the FDA in 1997, clopidogrel has been used in countless millions of patients as a therapy to reduce the risk of death or heart attack after a recent heart attack or stroke, and in people with peripheral arterial disease. With the loss of patent protection in 2012 the price difference immediately meant substantial savings for the 50 million people in the United States who had being buying clopidogrel at an average cost of $200 per month; and prices will continue to fall as more generic versions are approved, especially within the cash-strapped emerging markets.

About McCormack Pharma and CEME

The systems of correlation and association that formed the basis of CEME were first created in 1983 by Keith McCormack. Today, CEME (Cutting-Edge Medical Education), is a proprietary technology, developed by McCormack Pharma that is entirely unique within the pharmaceutical industry. CEME describes the use of customized relational databases with the capacity to rapidly mine data and discover previously-unknown relationships between product data and data for a licensed indication. These novel outputs constitute new teachings that, by improving patient management provide the means for enhanced brand awareness and increased sales.

Company contact
Keith McCormack PhD
Research Director
+44 (0) 20 8359 1218

Source: McCormack Pharma
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