Weston, ON - Major US pharmacies have started selling Apotex Corp's generic clopidogrel, despite protestations by the manufacturer and marketer of brand-name Plavix (Bristol-Myers Squibb (BMS)/Sanofi-Aventis). According to an Apotex spokesperson, the generic drug has been shipped out to pharmacies across the US—and just the US for now—and is being priced approximately 30% lower than Plavix, which costs approximately $4 per day.

Commenting on the potential impact of the generic drug, Dr Paul A Gurbel (Sinai Hospital of Baltimore, MD) emphasized its arrival should not alter how physicians currently use clopidogrel in clinical practice.

"The implementation of generics should not change the way doctors prescribe the drug," Gurbel told heartwire. "It has specific indications, and there will not be any alteration in what patients we use it in."

Where some experts expect they may see an impact, however, is in patient compliance. Patients who discontinue long-term clopidogrel due to its high cost face catastrophic consequences, physicians say, particularly if they're on the drug because they've received a drug-eluting stent.

"Certain practices that include large numbers of economically disadvantaged patients must deal with premature cessation of clopidogrel much more frequently than physicians would like to admit," Dr Peter Berger (Geisinger Health System, Danville, PA) told heartwire. "The consequences of stent thrombosis, which has as a risk factor the premature discontinuation of clopidogrel, are enormous. Over half of patients die or suffer a Q-wave MI. So if [availability of a generic] leads to greater compliance with medications, I would be thrilled."

Others, however, say it's too soon to hope that the introduction of one generic drug will produce any meaningful differences, because with only a 30% price difference, generic clopidogrel will still be too expensive for some.

Someone who was going to stop taking clopidogrel because it cost $4 a day is not going to not stop it at $3 a day.

"As a first step toward really affordable clopidogrel or affordable thienopyridine it's an important initial step that had to happen, but if you use the $4/day estimate, even by bringing the cost down to $3/day or a little bit less, it's still going to make it one of the most expensive medications a patient needs to take," Dr Steven Steinhbul (University of Kentucky, Lexington) told heartwire. "And to my mind it would be very unlikely to have an impact on who is or is not going to continue clopidogrel, because someone who was going to stop taking clopidogrel because it cost $4 a day is not going to not stop it at $3 a day."

For the price to drop, BMS/Sanofi will have to lower the price of brand-name Plavix—something some analysts predict it will do to compete with the generic, should Apotex ultimately come out the winner in patent litigation. This, in turn, may prompt further price slashing for the generic by Apotex. The advent of other generics will also help; Dr Reddy's Laboratories of India, for example, has also filed an abbreviated new drug application (ANDA) for generic clopidogrel and is still embroiled in litigation with Sanofi, while Teva Pharmaceuticals of Israel and Cobalt Pharmaceuticals of Canada have also declared their intentions to make generic clopidogrel. Apotex, however, has 180 days of marketing exclusivity as the first generic on the block.

Much depends on how courts handle requests by BMS/Sanofi to stop Apotex from selling its generic after the five-day delay earlier agreed to by the companies and ultimately on whether they uphold Plavix patents. Industry analysts have speculated that BMS made a mistake in the original settlement brokered between the companies when it agreed to reduce Apotex's liability if the settlement didn't go through, potentially waiving its right to seek treble damages or lost sales from Apotex. Analysts also do not agree on the likely outcome of the court battle, with many predicting it could go either way. A BMS spokesperson told heartwire on Wednesday that the company had no new comment on the matter.

Experts, meanwhile, say they believe a dipping drug price will increasingly have an impact on patients. "I do think that it is possible, even likely, that as the cost of clopidogrel comes down further, patients will be more compliant with the medication," Berger said. "And I do think that greater compliance with clopidogrel will reduce the frequency of stent thrombosis and other thrombotic events, assuming that the generic forms of clopidogrel are biologically equivalent—and I do not yet know if they are."