The Controversy over Acarbose 180-Day Exclusivity Heats Up

November 6, 2007

In September, we reported that FDA established a public docket (#2007N-0417) soliciting comment on certain 180-day exclusivity forfeiture and Orange Book patent “delisting” issues concerning the diabetes drug acarbose (marketed by Bayer Pharmaceuticals under the tradename PRECOSE).  Specifically, FDA’s September 26, 2007 letter states:

As of the date of this letter, which is more than 30 months from March 22, 2005, no first applicant’s ANDA has been approved. Also, on April 16, 2007, Bayer requested that the ‘769 patent be “delisted” as to Precose, i.e., they withdrew the patent information.  On September 26, 2007, FDA indicated in [the Orange Book] that the request to delist this patent had been submitted on April 16, 2007.

To determine whether any ANDA referencing Precose is eligible for final approval, the agency must consider how the 180-day generic drug exclusivity forfeiture provisions at section 505(j)(5)(D) of the [FDC Act] apply to this set of facts.  As part of the process for making such a determination, we are seeking your views regarding the applicability of sections 505(j)(5)(D)(i)(IV) — failure to obtain tentative approval within 30 months — and 505(j)(5)(D)(i)(I)(aa)(BB) — failure to market by 30 months. We also are interested in your views regarding the applicability of section 505(j)(5)(D)(i)(I)(bb)(CC) — relating to the delisting of a patent.

At that time, the identity of any first ANDA applicant eligible for 180-day exclusivity was not publicly known.  Since then, however, Cobalt Pharmaceuticals Inc. (“Cobalt”) has publicly disclosed its status as a first applicant. 

This became apparent when Cobalt submitted a 4-page emergency petition for stay of action in late October requesting that FDA stay the approval of all subsequent acarbose tablets ANDAs until Cobalt’s 180-day exclusivity period expires.  Cobalt argues that such a stay is necessary to prevent substantial and irreparable harm to the company.  “Here, Cobalt accepted the quid pro quo that Congress created with the exclusivity incentive and filed the first ANDA with a paragraph IV certification challenging the ‘769 patent.  As a reward, Congress intended that Cobalt reap the benefits of 180-day generic market exclusivity.  Sound public policy requires FDA to safeguard that exclusivity and to preclude others from circumventing it based on unlawful interpretations of the forfeiture provisions.” 

Upsher-Smith Laboratories (“USL”) and Teva Parenteral Medicines (“Teva”) submitted comments to docket #2007N-0417. (The deadline for submitting comments to the docket has been extended from October 10, 2007 until November 12, 2007.)  USL takes the position that because the ‘769 patent has been disclaimed, it should be removed from the Orange Book, and no first applicant should be awarded 180-day exclusivity — thereby making FDA’s solicitation unnecessary. 

Teva takes the position that the first applicant appears to have forfeited 180-day exclusivity eligibility because of a failure to obtain tentative ANDA approval within 30 months after the date on which the application was filed (i.e., FDC Act § 505(j)(5)(D)(i)(IV)).  Teva also comments on the “failure to market” and patent delisting forfeiture provisions at FDC Act §§ 505(j)(5)(D)(i)(I) and 505(j)(5)(D)(i)(I)(bb)(CC), respectively, on which FDA also requested comment. 

With respect to the “failure to market” provision, Teva states “we do not believe that, under the apparent facts of this case, the first applicant for generic Acarbose tablets has forfeited its exclusivity under [FDC Act § 505(j)(5)(D)(i)(I)].”  This position is consistent with Teva’s September 28, 2007 letter to FDA regarding 180-day exclusivity for generic granisetron (Docket #2007N-0389; 10/12/2007 FDA Law Blog post), in which the company takes the position that a first applicant’s failure to commence commercial marketing within 30 months of submitting its exclusivity-qualifying paragraph IV certification is not (on its own) sufficient to trigger 180-day exclusivity forfeiture.

With respect to the patent delisting forfeiture provision, Teva cites the District of Columbia Circuit’s 2006 decision in Ranbaxy Labs. Ltd. v Leavitt, and states:

[W]e do not believe that the reference to the withdrawal of patent information in [FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC)] abrogates the D.C. Circuit’s holding that FDA may not “delist a patent upon the request of the NDA holder [where] the effect of delisting is to deprive the applicant of a period of marketing exclusivity.”  Instead, the reference to delisting in [this forfeiture provision] merely reflects the fact that delisting may result from a court order entered pursuant to [FDC Act § 505(j)(5)(C)(ii)(I)], which for the first time authorized ANDA applicants who are sued by the NDA holder to “assert a counterclaim seeking an order requiring the holder to correct or delete the patent information submitted [to the Orange Book].”

We will continue to update you on this and other 180-day exclusivity issues for which FDA has recently requested public comment.

Categories: Hatch-Waxman