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$442 Million Fine Against Apotex for Plavix® Patent Infringement
Stent Patients Will Have to Wait for a Generic Version
Plavix and stent
Plavix and stents: the two
go together
    October 23, 2010 -- Apotex Inc., the largest Canadian-owned pharmaceutical manufacturer, has been hit with a $442 million fine by Judge Sidney H. Stein of the U.S. District Court, Southern District of New York (Manhattan) for patent infringement against Sanofi-Aventis (NYSE: SNY) and its partner Bristol-Myers (NYSE: BMY), regarding its marketing of a generic version of Plavix (clopidogrel), a drug widely used during and after angioplasty and stent placement. The fine results from a 2007 court decision, upholding Sanofi-Aventis' patent. The fine is significant for privately-held Apotex: almost half of its annual global sales for all products, reported to be around one billion Canadian dollars.

The generic version of Plavix was launched by Apotex on August 8, 2006, considered at the time a bold and "at-risk" move, due to the patient dispute. Apotex immediately flooded the market with its generic clopidogrel, resulting in sales of $884 million. 24 days later, Judge Stein granted Sanofi/Bristol-Myers' request for an injunction, and this week's penalty represents half of Apotex sales during this short period.

Plavix and Stents
Plavix is an antiplatelet drug which prevents blood from clotting. In at risk individuals, a blood clot (also called thrombosis) can cause a heart attack or other coronary problems. It is routinely given to patients, along with aspirin, after stent implantation for 1-2 months following a bare metal stent (BMS) and for 12 months or more when a drug-eluting stent (DES). The drugs help prevent platelets from congregating along the exposed metal struts of the stent and forming clots. However, because of concerns about late and very late stent thrombosis (clots occurring later than 6 months and up to two or three years) there has been much controversy over how long Plavix should be given to DES recipients, with many cardiologists prescribing the drug for life.

Duration of Dual Anti-Platelet Therapy (DAPT)
Although the question of how long drug-eluting stent patients need to stay on Plavix and aspirin was first raised in a two-day FDA stent safety panel in 2006, it took three years for a large scale clinical trial (over 20,000 patients at 254 locations) to begin enrollment. The DAPT Study, being conducted by the Harvard Clinical Research Institute, will cost many millions of dollars and is being supported by the four major stent companies (Abbott, Medtronic, Cordis and Boston Scientific) along with the companies that make and market Plavix (Bristol-Myers Squibb and Sanofi-Synthelabo) and those that make and market the newest antiplatelet drug Effient (Eli Lilly and Daiichi Sankyo Inc.). Results of DAPT won't be known for at least four more years (final data collection is scheduled for December 2013). Interestingly, this trial began only months after the FDA approved Effient (prasugrel) -- a potential competitor to Plavix.

DAPT will compare outcomes of stent patients who take 12 months of Plavix or Effient (plus aspirin) with those who stay on the drugs for 30 months. The question of whether or not there's any difference in six months of DAPT (the original FDA recommendation for drug-eluting stents) will not be addressed, although other smaller trials with Medtronic's Endeavor stent, which is said to heal more quickly, are exploring that question.

Plavix: The Third Largest-Selling U.S. Drug
Plavix ranks third in U.S. sales of prescription medicine, topping $4.2 billion for 2009 (up 11% from 2008). At $5.29 for a 75mg tablet (the latest online pharmacy price from this correlates to slightly over two million patients taking one a day annually. Most estimates of angioplasties performed annually in the U.S. range from 700,000 to one million -- meaning that a very significant portion of Plavix sales are to stent recipients. Another interesting fact is that receipt of a stent is NOT technically an "on-label" indication for Plavix (see "FDA Policy on Plavix and Stents: Catch-22").

Furthermore, many patients who receive stents may not be aware of the clinical need for long-term medications, and may not realize the financial implications. Although most medical insurance policies cover the stent placement itself, many do not reimburse for the $2,000 annual Plavix prescription. A sampling of problems patients are facing can be read on Angioplasty.Org's Forum Topic, "Financial Assistance for Plavix". Many interventional cardiologists have taken to assessing whether or not their patients will be able to afford Plavix for a year or more and, if not, they implant the older bare metal stent.

Reported by Burt Cohen, October 23, 2010