District Court Sides with FDA, 505(b)(2) Applicant in Challenge to Colchicine Capsules Approval; An Appeal is in the Works, However

By Kurt R. Karst –      

A little over three months ago, we on a Complaint and a Motion for Temporary Restraining Order and Preliminary Injunction Takeda Pharmaceuticals U.S.A., Inc.’s (“Takeda”) filed against FDA in the U.S. District Court for the District of Columbia challenging the Agency’s September 26, 2014 approval of a 505(b)(2) application (NDA 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.  Takeda is the holder of NDA 022352 for COLCRYS (colchicine) Tablets, 0.6 mg, which FDA approved back in 2009 to prevent gout, treat gout flares, and treat Familial Mediterranean Fever.  The Orange Book currently list a single period of unexpired non-patent exclusivity for COLCRYS, as well as information on several patents that expire in 2028 and 2029.  The MITIGARE NDA does not cite COLCRYS as a listed drug relied on for approval, but rather a different drug: COLBENEMID, a fixed-dose combination drug product containing probenecid (500 mg) and colchicine (0.5 mg) FDA approved under NDA 012383 on July 27, 1961, that is no longer marketed, and for which no patents are listed in the Orange Book.  That choice of listed drug for the MITIGARE 505(b)(2) NDA is at the heart of Takeda’s early October 2014 lawsuit against FDA. 
 
Briefly, Takeda alleges that FDA’s approval of MITIGARE violates the FDC Act and the Administrative Procedure Act 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. 

A lot has happened since early October.  Here are some highlights . . . .

• On November 4, 2014, three related entities – Elliott Associates, L.P.,  Elliott International, L.P., and Knollwood Investments, L.P. (collectively “Elliott”) – with investment interests in COLCRYS filed a separate Complaint against FDA in the D.C. District Court challenging the Agency’s approval of MITIGARE along the same lines as Takeda.  Elliott also filed a Motion for Summary Judgment in its case.  D.C. District Court Judge Ketanji Brown Jackson subsequently determined that the two cases should be considered in tandem.
• On November 5, 2014, Judge Jackson converted Takeda’s Motion for a Preliminary Injunction into a Motion for Summary Judgment by consolidating Takeda’s Motion for a Preliminary Injunction with the merits of Takeda’s case against FDA.  Also, Judge Jackson subsequently permitted Hikma and West-Ward to intervene in the case.
• Cross-Motions for Summary Judgment were subsequently filed by FDA (here) and Hikma/West-Ward (here) in the Elliott case.  (Additional briefs filed in the cases along the way are available here, here, here, here, here, and here.)
• Meanwhile, in a patent infringement action Takeda filed against Hikma and West-Ward in early October in the U.S. District Court for the District of Delaware, see Takeda Pharmaceuticals U.S.A., Inc. v. West-Ward Pharmaceutical Corporation et al, Case No. 1:14-cv-01268-SLR, that district court issued a Temporary Restraining Order (on October 9, 2014) preventing Hikma from marketing MITIGARE.  Later, the district court denied Takeda’s request for a Preliminary Injunction, which Takeda appealed to the U.S. Court of Appeals for the Federal Circuit, but granted an injunction pending appeal.  On January 9, 2015, the Federal Circuit issued an Order (Memorandum Opinion to follow) affirming the Delaware District Court’s Order denying Takeda’s Motion for Preliminary Injunction, and vacating the injunction pending appeal ordered by the Delaware District Court.

That brings us to Judge Jackson’s January 9, 2015 Order.  In it, Judge Jackson denied Takeda’s Motion for Summary Judgment, denied Elliott’s Motion for Summary Judgment in the separately filed action, and granted FDA’s and Hikma’s/West-Ward’s Cross-Motions for Summary Judgment in the Elliott action.  Those decisions led Judge Jackson to order the dismissal of the Elliott action, and also to order that Takeda show cause (on or before January 23, 2015) as to why the D.C. District Court should not dismiss Takeda’s lawsuit sua sponte. 

Unfortunately, Judge Jackson's Memorandum Opinion providing the basis for her decisions is not yet public.  It was issued under seal on January 12, 2015 is is reportedly "quite lengthy."  (A response to the court's Order to Show Cause as to why the Memorandum Opinion should not be made public is due by January 23, 2015.)  So consider this post as a setup to a further discussion of the issues in the case once the decision is unsealed. 

Regardless of when Judge Jackson’s Memorandum Opinion will issue, it appears that the parties will fight on.  Shortly after Judge Jackson’s Order was handed down last Friday, Takeda and Elliott separately filed an Emergency Motion for Injunction Pending Appeal (here and here).  FDA and Hikma/West-Ward promptly opposed the motions (here and here).

The battle over FDA’s approval of MITIGARE is not the only battle over a 505(b)(2) application we’re keeping a close eye on these days.  As we previously reported, FDA was sued in December after the Agency granted only a tentative approval to Veloxis Pharmaceuticals, Inc.’s 505(b)(2) NDA 206406 for ENVARSUS XR (tacrolimus extended-release tablets), 0.75 mg, 1 mg, and 4 mg, for prophylaxis of organ rejection in kidney transplant patients.  That battle, which concerns the scope of 3-year non-patent exclusivity, has been on hold until FDA issues a decision on the underlying merits in the matter.  FDA was supossed to have issued a decision on January 12, 2015.  The parties were ordered to appear before the court for a status hearing on January 14, 2015. 

UPDATE:

• The following Minute Order was entered late on January 12, 2015: "MINUTE ORDER denying Takeda's Emergency Mot. for Inj.  Relief Pending Appeal and Elliott's Mot. for Inj. Pending Appeal and Joinder in Takeda's Mot. for Same.  This Court issued an order denying Plaintiffs' motions for summary judgment on January 9, 2015, and filed a lengthy opinion stating the reasons for that order today. (See Order, ECF No. 68; see also Mem. Op., ECF No. 74.)  Plaintiffs have now moved for a stay of this Court's order pending appeal.  "A party who moves for a stay or injunction pending appeal bears the burden of showing [that] the balance of four factors weigh[s] in favor of the stay/injunction: (1) the likelihood that the party will prevail on the merits of the appeal; (2) the likelihood that the party will be irreparably harmed absent a stay; (3) the prospect that others will be harmed if the court grants the stay; and (4) the public interest in granting a stay."  McCammon v. United States, 584 F. Supp. 2d 193, 197 (D.D.C. 2008) (citing United States v. Philip Morris USA, Inc., 449 F. Supp. 2d 988, 990 (D.D.C. 2006)).  In considering such a motion, the Court must be mindful of the fact that "a stay pending appeal is 'always an extraordinary remedy,' and that the moving party carries a heavy burden to demonstrate that the stay is warranted."  Philip Morris, 449 F. Supp. at 990 (quoting Brotherhood of Railway and Steamship Clerks, Freight Handlers and Station Employees v. National Mediation Board, 374 F.2d 269, 275 (D.C. Cir. 1966)).  With that standard in mind, this Court has considered the applicable factors and concludes that the balance of these factors weighs against entering the injunction that Plaintiffs seek.  Plaintiffs are unlikely to prevail on the merits of their appeal for the reasons stated in this Court's opinion denying their motions for summary judgment, and whatever economic harm that Plaintiffs may suffer in the absence of a stay is outweighed by the harms that the Defendant-Intervenors and the public at large will suffer as a result of a stay. Consequently, Plaintiffs' Motions for Stay Pending Appeal are DENIED."