Par Fights FDA Forfeiture Of Generic Colcrys Exclusivity

Pursing legal action against the agency in an area where it is sometimes vulnerable, Par argues that amending its proposed label did not interrupt paragraph IV certification for the firm's colchicine ANDA.

Can an ANDA sponsor forfeit 180-day market exclusivity for its generic by amending its proposed label?

That appears to be the question at the center of Par Pharmaceutical Inc.’s suit against FDA. The complaint says that on Sept. 28, FDA sent a letter to Par (now a unit of Endo Pharmaceuticals Inc.) stating that the company had not maintained an uninterrupted paragraph IV certification “with respect to any claims” in two of Takeda Pharmaceuticals USA Inc.’s Colcrys (colchicine) patents and thus had forfeited its eligibility for 180-day exclusivity.

FDA has faced numerous suits over its application of the provisions of the Medicare Modernization Act of 2003, which specify triggers under which the first ANDA filer forfeits 180-day exclusivity. One trigger occurs when “the first applicant amends or withdraws the certification for all of the patents with respect to which that applicant submitted a certification qualifying the applicant for the 180-day exclusivity period.”

Par contends that it maintained paragraph IV certification with respect to at least claims 1 and 7 of Takeda patent No. 7,964,648, which covers treatment of both gout and familial Mediterranean fever.

Par sent a notice letter to Takeda in March 2012 with a paragraph IV certification that certain Colcrys patents listed in FDA’s Orange Book were invalid or would not be infringed by Par’s generic. The notice included a section viii statement carving out indications covered by other patents, and a “split certification” for the ‘648 patent. Takeda sued Par for infringement and the parties reached a settlement agreement in September 2014.

“The initial paragraph IV position was never altered, from submission to the present day,” Par’s complaint states.

During the course of the litigation, Takeda obtained additional patents that were listed in the Orange Book. In July 2013, Par submitted a labeling amendment removing the gout indications from its proposed label and replacing them with the familial Mediterranean fever indication. At the same time, Par submitted a corresponding patent amendment.

Specifically, the suit says Par changed its paragraph IV certifications to section viii statements with respect to gout-based claims, and section viii statements to paragraph IV certifications with respect to the familial Mediterranean fever-based claims, but it never changed its paragraph IV certifications with respect to claims 1 and 7, which are directed solely to methods of treating a patient with colchicine when the patient is also being administered ketoconazole.

“Inasmuch as the claim itself would embrace a method that is equally applicable to either disease, the initial paragraph IV position was never altered, from submission to the present day,” the complaint states.

“As such, there is no basis in the law or regulations for FDA to determine that Par forfeited its eligibility for 180-day exclusivity for colchicine tablets USP, 0.6 mg,” Par says.

FDA Loses Some 180-Day Exclusivity Suits

Par’s suit, filed Sept. 29 in the US District Court for the District of Columbia, seeks a court ruling that the agency’s decision is arbitrary, capricious and contrary to law. It also requests an injunction prohibiting FDA from approving any other colchicine ANDA prior to Par’s and staying the effective approval of any other ANDA that has been approved.

FDA granted tentative approval to Par’s colchicine ANDA on Feb. 12, 2015 and Watson Laboratories Inc.’s (now Teva Pharmaceutical Industries Ltd.’s) ANDA on Oct. 6, 2015.

Colchicine products for the treatment of gout had been on the market for decades before Congress enacted the 1962 amendments to the Food, Drug, and Cosmetic Act requiring that a drug be shown to be effective as well as safe prior to marketing. Many companies, including Takeda, withdrew their colchicine products from the market after FDA took enforcement action against unapproved single-ingredient oral colchicine products in 2006.

This is the second time FDA has been hit with a lawsuit involving Colcrys. Takeda sued the agency claiming it should not have approved Hikma Pharmaceuticals PLC’s colchicine drug Mitigare because the company’s application did not reference Colcrys or certify to Colcrys patents. A judge dismissed the suit last year finding that FDA’s procedural rules did not require Hikma to reference Colcrys because the company did not rely on Colcrys data to support its application and Hikma’s product is not a duplicate of Colcrys. (Also see "Takeda’s Take On Patent Certification Rules In Colchicine Dispute Rejected" - Pink Sheet, 21 Jan, 2015.)

FDA generally prevails in disputes over 180-day exclusivity but it has lost some cases. For example, in 2010 the US Court of Appeals for the District of Columbia Circuit overturned a DC district court decision that found FDA had correctly interpreted the Medicare Modernization Act in denying Teva 180-day exclusivity for generic versions of Merck & Co. Inc.’s hypertension drugs Cozaar (losartan) and Hyzar (losartan/hydroclorothiazide) because Merck had delisted the patents in FDA’s Orange Book. (Also see "FDA Hit With Slew Of Suits As Firms Fight For Market Advantage" - Pink Sheet, 26 Nov, 2012.)

And in 2014, the US Court of Appeals for the Fourth Circuit overturned FDA’s approach to awarding generic marketing exclusivity for Pfizer Inc.’s Celebrex (celecoxib). In that case, the agency had treated an original and reissued patent as a "single bundle of rights" under the framework in place prior to the MMA. (Also see "Celebrex Generic Exclusivity Suit Could Have Broad Financial, Regulatory Reach" - Pink Sheet, 22 Dec, 2014.)