Flare Up: Takeda Challenges FDA Approval of 505(b)(2) Application for Colchicine Capsules

October 8, 2014

By Kurt R. Karst –  

Colchicine is one of those drugs that has a long and storied history at FDA.  It’s an old drug (about 200 years old) that was marketed for decades without FDA approval.  Then, in 2009, FDA approved Mutual Pharmaceutical Company, Inc.’s (and now Takeda Pharmaceuticals U.S.A., Inc.’s (“Takeda”)) 505(b)(2) application (NDA No. 022352) for COLCRYS (colchicine) Tablets, 0.6 mg, to prevent gout, treat gout flares, and treat Familial Mediterranean Fever (“FMF”) and granted periods of 3-year new clinical investigation exclusivity (related to the gout approvals) and a period of 7-year orphan druig exclusivity (related to FMF).  Soon after the NDA approval, there was litigation to stem the flow of unapproved colchicine (see our previous posts and here).  And about a year after NDA approval, FDA ordered companies marketing unapproved single-ingredient oral colchicine to remove their products from the market.  Companies that wanted to market generic or follow-on versions of single-ingredient oral colchicine then began to consider their options: submit an ANDA or a 505(b)(2) application.  And while those decisions were being made, the citizen petition process was initiated, with no less than two petitions: Docket Nos. FDA-2010-P-0614 and FDA-2012-P-1018.  Now the storied history of colchicine is about to get longer . . . .
Earlier this week, Takeda filed a Complaint in the U.S. District Court for the District of Columbia challenging FDA’s September 26, 2014 approval (here and here) of a 505(b)(2) application (NDA No. 204820) submitted by Hikma Pharmaceuticals LLC (“Hikma”) and its U.S. partner West-Ward Pharmaceutical Corp. (“West-Ward”) for MITIGARE (colchicine) Capsules, 0.6 mg, for prophylaxis of gout flares.  Although there are several patents listed in the Orange Book for COLCRYS, this is the first opportunity Takeda has had to challenge MITIGARE.  Apparently Hikma was able to avoid identifying COLCRYS as a listed drug in its 505(b)(2) application by virtue of relying on information not containd in (or related to) the COLCRYS NDA approval, and therefore avoid certifying to Orange Book-listed patents for COLCRYS.

Takeda alleges in its October 6, 2014 Complaint that FDA’s approval of MITIGARE violates the FDC Act and the Administrative Procedure Act (“APA”) in several respects:

First, FDA acted arbitrarily and capriciously in approving Hikma’s Section 505(b)(2) application for Mitigare without requiring the label to contain critical safety information that FDA previously stated was necessary for single-ingredient oral colchicine products.  Second, FDA’s approval of Hikma’s application for Mitigare was unlawful, arbitrary and capricious because, as approved, Mitigare is not safe in light of the defects in its label.  And third, FDA’s failure to require Hikma to reference Takeda’s own colchicine drug, Colcrys®, in its application interfered with Takeda’s rights to participate in the administrative process, including the Paragraph IV certification process under the Hatch-Waxman Act and the Citizen Petition process. As a result, FDA’s decision is unlawful, arbitrary, capricious, an abuse of discretion, and otherwise violates the Administrative Procedure Act (the “APA”).

Takeda’s Complaint fills in some of the details of the allegations.  For example, Takeda, citing to one of the FDA petition responses concerning colchicine (i.e., FDA-2010-P-0614), says that “[e]ven though Mitigare is indicated only for prophylaxis, FDA has clearly stated that the labeling for a prophylaxis product must disclose the dosage for treatment of an acute gout flare due to the risk of cumulative toxicity,” but that the MITIGARE labeling omits that low-dose regimen information, as well as “specific dose adjustments to avoid potentially fatal drug-drug interaction.”  Having omitted this information, “Hikma was able to avoid referencing Colcrys® and certifying to the Colcrys® patents,” alleges Takeda.  Takeda also alleges that MITIGARE fails to meet the statutory standard required for FDA approval because the labeling omits certain safety information.  

Takeda is seeking declaratory and injunctive relief.  Specifically, Takeda wants the court to declare that FDA’s approval of MITIGARE violated the APA and the FDC Act, that FDA’s refusal to require the MITIGARE 505(b)(2) application to reference COLCRYS as a listed drug violated the APA and the FDC Act, and that FDA’s actions, findings, and conclusions in approving MITIGARE were arbitrary, capricious, an abuse of discretion, and without factual basis.  In addition, Takeda wants temporary, preliminary and permanent injunctive relief requiring FDA to rescind or stay FDA’s approval of MITIGARE.  A redacted version of Takeda’s  memorandum in support of the company’s Motion for a Temporary Restraining Order and Preliminary Injunction should be available soon, and will be included as an update to this post. 


  • A redacted version of Takeda's brief accompanying its Motion for Temporary Restraining Order and Preliminary Injunction filed in the DC District Court was made available on October 8th.
  • A Telephone Conference is set for October 9th at 1:00 PM before Judge Ketanji Brown Jackson (DC District Court).
  • On October 3, 2014, Takeda filed a patent infringement lawsuit against West-Ward in the U.S. District Court for the District of Delaware: Takeda Pharmaceuticals U.S.A., Inc. v. West-Ward Pharmaceutical Corporation et al, Case No. 1:14-cv-01268-SLR.  A telephonic hearing on Takeda's Motion for Temporary Restraining Order and Preliminary Injunction in that case was held on October 8th.
  • October 9, 2014: "Minute Entry for proceedings held before Judge Ketanji Brown Jackson: Telephone Conference held on 10/9/2014 discussions re: Temporary Restraining Order. Government Brief due by 10/17/2014; Intervenor Brief, if any, shall be filed by 10/17/14; Responses due by 10/20/2014. Preliminary Injunction Hearing set for 10/21/2014 @ 2:30 PM in Courtroom 17 before Judge Ketanji Brown Jackson. Motion to Intervene GRANTED for reasons stated on the record."