Lawsuit Against FDA over VYVANSE NCE Exclusivity Put on Ice While FDA Solicits Public Comment

By Kurt R. Karst –      

We recently reported on a complaint filed in the U.S. District Court for the District of Columbia by Actavis Elizabeth LLC (“Actavis”) against FDA in which Actavis requested the court to enter an injunction directing FDA to rescind the Agency’s grant of 5-year New Chemical Entity (“NCE”) exclusivity for the ADHD drug VYVANSE (lisdexamfetamine dimesylate) Capsules.  NCE exclusivity was created under Title I of the 1984 Hatch-Waxman Amendments.

Actavis filed the lawsuit after the company submitted and FDA refused to accept an ANDA for a generic version of VYVANSE earlier this year.  FDA’s Orange Book states  that VYVANSE is a Type 1 new molecular entity covered by a period of NCE exclusivity that is scheduled to expire on February 23, 2012.  The VYVANSE labeling states that the drug product is a therapeutically inactive pro-drug that is metabolically converted to dextroamphetamine, a previously approved drug (e.g., ADDERALL).  Actavis states in its complaint that FDA should not have granted 5-year NCE exclusivity for VYVANSE, and that “FDA’s blanket distinction between covalent derivatives and non-covalent derivatives for purposes of awarding NCE exclusivity is inconsistent with the FDCA, its legislative history and FDA’s own regulations.” 

On April 13, 2009, the court granted an Unopposed Motion to Stay Proceedings pending further order of the court.  According to the Unopposed Motion to Stay Proceedings, “Actavis sued FDA . . . before the agency had a meaningful opportunity to consider the arguments that Actavis had raised in its February 6, 2009 brief concerning the application of the governing statute and regulation . . . .”  FDA also stayed its decision refusing to accept Actavis’ ANDA and opened a public docket (Docket No. FDA-2009-N-0184) to solicit comment on the issues raised by Actavis.  FDA anticipates that the docket will close with an Agency decision by September 25, 2009.  Comments are due to FDA by June 1, 2009. 

FDA’s letter soliciting public comment includes a February 6, 2009 letter brief submitted to the Agency on behalf of Actavis supporting the company’s position that FDA erroneously awarded 5-year NCE exclusivity to VYVANSE.  According to that letter brief:

In granting NCE exclusivity to Vyvanse, FDA appears to have applied a blanket rule that all covalent derivatives other than esters should be considered “active ingredients” (or “active moieties”), while non-covalent derivatives should not.  This rigid distinction between covalent and non-covalent derivatives, however, is arbitrary and capricious and contrary to the plain meaning of the statute and its legislative history.  Specifically, [FDC Act §] 505(j)(5)(F)(ii) directs that NCE exclusivity be based on the approval of a new “active ingredient,” which in the context of this provision means a new active moiety.  The active moiety, in turn, is the molecule or ion (or portion thereof) that provides the therapeutic effect at the site of drug action.  FDA’s blanket distinction between covalent derivatives and non-covalent derivatives for purposes of awarding NCE exclusivity is inconsistent with the statute, its legislative history and, indeed, FDA’s own regulations.  Instead, an award of NCE exclusivity should focus on the active moiety, i.e., the molecule or ion (or portion thereof) that provides the therapeutic effect at the site of drug action.

Interestingly, the meaning of the terms “active ingredient” and “active moiety” have also recently been the subject of litigation for purposes of Patent Term Extensions (“PTE”), which were created under Title II of the 1984 Hatch-Waxman Amendments.  As we previously reported, in late March 2009, the U.S. District Court for the Eastern District of Virginia sided with PhotoCure ASA in a lawsuit against the U.S. Patent and Trademark Office (“PTO”), and applied an “active ingredient” interpretation instead of the PTO’s  “active moiety” interpretation with respect to a PTE request for METVIXIA (methyl aminoevulinate hydrochloride).  It seems likely that the PTO will appeal that decision.