Toronto, ON - Apotex Corp (Toronto, ON) today launched its version of generic clopidogrel bisulfate 75-mg tablets, backing out of a settlement agreement with Plavix manufacturer and marketers Bristol-Myers Squibb (BMS) and Sanofi-Aventis that would have delayed a generic version for another five years.

Earlier today, BMS had announced in a filing with US regulators that it predicted the arrival of a generic drug on the market soon. BMS has held the patent for Plavix since 1997; it is marketed by Sanofi-Aventis outside the US.

Both BMS and Sanofi have said they will be exploring ways of blocking the generic's sales, although a New York judge has already denied a request from the companies to do so. An earlier agreement reached between the three companies prevents Sanofi and BMS from putting a temporary restraining order on an Apotex launch. They are also prohibited from seeking a preliminary injunction until at least five business days after Apotex begins shipments, the Apotex press release notes.

Apotex has 180 days of market exclusivity for the product, since it was the first generic company to file an abbreviated new drug application (ANDA) with the FDA, the press release also points out. However, should successive litigation find Apotex guilty of patent infringement, the company faces the prospect of paying millions in damages.

Apotex actually obtained the ANDA in January 2006 and had entered into the settlement agreement in March, putting an end to patent litigation. In the settlement, Apotex agreed to not sell its generic drug until 2011, slightly before patent expiration, in return for payments from BMS and Sanofi-Aventis, rumored to start at $40 million. Late last month, however, a group of US state attorneys general rejected the deal. Meanwhile, the US Department of Justice is conducting a criminal investigation of antitrust activity at BMS and Sanofi: media reports note that the FBI has confiscated documents at BMS's Manhattan head office, while both companies have been served with grand jury subpoenas.

In the announcement today, Apotex CEO Dr Barry Sherman said, "We are confident that the patent will be held invalid and that the courts will find inequitable conduct before the Patent Office on the part of Sanofi. Accordingly, Apotex has launched prior to trial so that patients and public and private healthcare payers can begin benefiting from a quality, low-cost alternative to Plavix immediately rather than years from now."

Meanwhile, Tony Plohoros, a BMS corporate spokesperson, told heartwire that the company will be seeking "injunctive relief" to defend its patent. "We believe the patent is valid and that it has been infringed and together with our partner, Sanofi-Aventis, will vigorously defend our intellectual property rights. We are actively evaluating legal and commercial options available to us."

Under the preexisting agreement, he adds, all parties were required to cooperate and use all reasonable efforts to facilitate regulatory review of the agreements.

In the press statement, Sherman declares that the company's decision to move ahead now with generic clopidogrel "is a testament to our commitment to patients, consumers, and taxpayers."

Plohoros disagrees. "Generic Plavix is not good news for patients. In the long-term, an at-risk launch of generic clopidogrel by Apotex would have an adverse impact on the long-term research and development plans for Plavix and other products we are developing. Bristol-Myers Squibb and its partner, Sanofi-Aventis, have a long-term R&D plan for Plavix that could not be sustained with the exclusivity loss that the Apotex launch would cause."

More broadly, he said, "intellectual property rights are essential for the research-based pharmaceutical and biotech industry to continue to develop innovative medicines to treat serious diseases. Decisions that weaken patent protection and allow early generic entries into the market before the original patent expires, as in this case, ultimately result in a negative environment for research and development in general and adversely affect the industry's innovation model, to the detriment of patients."

Plavix reaped more than $6 billion in sales last year, one of the world's top-selling drugs. Shares at BMS had fallen almost 7% on Tuesday.