New genetic test for Plavix efficacy in the works?

The blockbuster anti-clotting drug Plavix is prescribed to patients with coronary artery stents to prevent re-thrombosis. Now, months after the FDA called for warning labels indicating that the drug — marketed by Sanofi-Aventis and Bristol Myers Squibb — may not be effective due to genetic propensity towards drug resistance in some patients, German scientists announced in the journal Nature Medicine that they had stumbled upon a new genetic marker that distinguishes patients who will respond better to the drug. The German scientists reported that the enzyme paraoxonase-1 (PON1) is required to activate Plavix (known generically as clopidogrel) and prevent clotting. Using a metabolic assay, the researchers determined that coronary artery disease patients with a particular mutation in PON1 were able to activate the drug more effectively and thus inhibit clotting. An earlier study found that a mutation in another gene, cytochrome P450 2C19, is the primary predictor of Plavix efficacy. This study found no such association.

“This is a great example of the valuable application of pharmacogenetics to provide individualized medicine based on personal genotype,” says ACSH's Dr. Gilbert Ross. “Determining whether the drug is inhibiting clotting is not a lab test which is readily available, nor is it cheap. So, the availability of a genetic test to predict whether a patient will respond well to this drug will enable physicians to more easily determine the best treatment options. Not all patients respond well to a given drug and because Plavix is such a big seller, this affects a lot of people.”

ACSH's Dr. Elizabeth Whelan adds that this development “goes against the argument that you don’t need more than one drug for a particular condition. It’s a good thing that there is an alternative to Plavix — Effient or prasugrel — for those patients who do not benefit from it.”