FDA is Petitioned Twice More to Delay Start of Hatch-Waxman Exclusivity

By Kurt R. Karst –      

The number of citizen petitions pending at FDA concerning Hatch-Waxman exclusivity continues to pile up.  As we previously reported (here and here), FDA has already been asked on three separate occasions in 2013 to recognize 5-year New Chemical Entity (“NCE”) exclusivity for a fixed-dose combination drug product containing both a never-before-approved active moiety and a previously approved active moiety: (1) NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets (Docket No. FDA-2013-P-0471); (2) STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets (Docket No. FDA-2013-P-0058); and (3) PREPOPIK (sodium picosulfate, magnesium oxide and citric acid) for Oral Solution (Docket No. FDA-2013-P-0119).  Later on in the year, Eisai Inc. (“Eisai”) petitioned FDA – Docket No. FDA-2013-P-0884 – arguing that the Agency erroneously triggered 5-year NCE exclusivity for BELVIQ (lorcaserin HCl) Tablets and FYCOMPA (perampanel) Tablets before the drugs were scheduled by the Drug Enforcement Administration (“DEA”) under the Controlled Substances Act (“CSA”), and thus, before commercial marketing could occur (see our previous post here).  Now come two more petitions on Hatch-Waxman exclusivity – one petition (Docket No. FDA-2013-P-1397) from UCB, Inc. (“UCB”) concerning 5-year NCE exclusivity for VIMPAT (lacosamide), and another petition (Docket No. FDA-2013-P-1376) from Covis Pharma S.à.r.l. (“Covis”) concerning 3-year new clinical investigation exclusivity for LANOXIN (digoxin) Tablets.  A denial of any one or more of these six petitions could very well end up in court with a potentially landscape-changing result.  Below is a run-down of the two latest citizen petitions.

VIMPAT (lacosamide) – Docket No. FDA-2013-P-1397

Similar to Eisai, UCB argues in its petition that FDA erroneously started the clock running on NCE exclusivity for lacosamide before scheduling of the drug under the CSA was completed by the DEA, thereby paving the way for UCB to market the product.  According to UCB, 233 days of exclusivity was lost, because lacosamide was not scheduled until May 21, 2009 when the DEA issued a final rule placing the drug into Schedule V,  “and the Department of Justice’s letter to each House of the Congress and the Comptroller General, transmitting the final rule scheduling lacosarnide, was received on June 9, 2009.” 

FDA has approved three NDAs for UCB’s lacosamide: NDA No. 022253 (tablets; approved on October 28, 2008), NDA No. 022254 (intravenous solution; approved on October 28, 2008), and NDA No. 022255 (oral solution; aproved on April 20, 2010).  In addition to the same two patents listed in the Orange Book for all three dosage form NDAs, the Orange Book also lists a period of NCE exclusivity that expired on October 28, 2013.  According to FDA’s Paragraph IV Certifications List, the Agency received ANDAs containing Paragraph IV certifications for generic versions of VIMPAT Oral Solution and VIMPAT Tablets on Monday, October 29, 2012 (the so-called NCE-1 date).  In fact, UCB says in the petition that the company received 19 Paragraph IV certification notices from 16 different companies!  (Possibly a new Hatch-Waxman record.)

Although UCB adopts the rational proffered by Eisai in its petition, UCB’s requested action differs somewhat from that of Eisai, likely because of the expired status of NCE exclusivity for the drug.  In addition to requesting that FDA “determine that the NCE exclusivity for lacosamide began on June 9, 2009, and thus will end on June 9, 2014,” UCB requests that FDA “confirm that the Agency will stay approval of [pending ANDAs], and any additional ANDA that meets the criteria under [FDC Act § 505(j)(5)(B)(iii)], absent another specified event under [FDC Act § 505(j)(5)(B)(iii)], until December 7, 2016.”  That is, UCB requests that the 30-month litigation stay on ANDA approval be extended from April 28, 2016, which is 7.5 years after NCE NDA approval, until December 7, 2016, which is 7.5 years after NCE NDA approval plus 223 days (or simply 7.5 years after UCB argues NCE exclusivity began). 

Curiously, UCB does not argue that each of the Paragraph IV ANDAs submitted to FDA on October 29, 2012 should be rejected as premature.  After all, if the NCE exclusivity began on June 9, 2009 as UCB argues, then the NCE-1 date for Paragraph IV ANDA submissions would have been June 9, 2013.  In that case, the ANDAs submitted in October 2012 were premature and should have been rejected by FDA. 

LANOXIN (digoxin) Tablets – Docket No. FDA-2013-P-1376

In what Covis says is a case of first impression, the company argues in its petition that FDA erroneously determined that periods of 3-year new clinical investigation that were granted with respect to two strengths of LANOXIN (digoxin) Tablets – 0.0625 mg and 0.1875 mg – have expired.  FDA approved six strengths of LANOXIN under NDA No. 020405 on September 30, 1997: 0.125 mg, 0.250 mg, 0.375 mg, 0.500 mg, 0.0625 mg, and 0.1875 mg.  Only two strengths have been marketed since NDA approval: 0.125 mg and 0.250 mg.  According to the 2000 edition of the Orange Book, the period of 3-year exclusivity for each strength (coded as “I-194” and defined in an Orange Book addendum as “CONGESTIVE HEART FAILURE”) expired on September 30, 2000. 

Although Covis does not disagree with FDA’s decision to aware 3-year exclusivity for all six strengths, the company contends that the periods of exclusivity for the 0.0625 mg and 0.1875 mg strengths did not begin to run until October 17, 2013 when FDA approved a Prior Approval Supplement (“PAS”) for them:

FDA’s complete administrative record for NDA 20-405 shows that the Agency only fully approved two of the six dosage strengths in that NDA.  This fact is confirmed by the Agency’s requirement that Covis submit a [PAS], CMC dissolution data for the new strengths (0 .0625 mg and 0.1875 mg), and draft labeling for the new strengths, and that FDA conduct a prior approval inspection.  The FDA inspector also directed Covis to be in compliance with all blend uniformity testing requirements. . . .  In the present case, the awarded exclusivity did not begin running for the four never-marketed strengths.  These four strengths could not have been fully approved in 1997 because FDA would not permit Covis to market the two new strengths before the Agency reviewed and approved new data and information.  Covis has only now submitted a PAS with necessary labeling – an approval requirement for an NDA or an [ANDA].  Furthermore, Covis has only now submitted contemporary CMC dissolution data, another pre-approval requirement.  These elements of approval, coupled with the prior approval inspection of Covis’ contract manufacturer and FDA’s direction that Covis comply with all appropriate blend uniformity testing requirements, confirm that this data and information are critical pre-approval and not post-approval requirements.  This conclusion is confirmed by the Agency’s administrative record for this NDA, particularly FDA’s 1997 approval letter and the 2012-2013 communications between FDA and Covis regarding the new strengths.

Although the petition does not specifically concern the two remaining never-before marketed strengths – 0.375 mg and 0.500 mg – Covis would presumably argue that a similar argument would apply to them if they are subsequently approved in a PAS.  

Accordingly, Covis requests that FDA:

(1) Confirm that the Agency did not fully approve the 0.0625 mg and 0.1875 mg tablets on September 30, 1997 in NDA 20-405 because of: (a) the language in the administrative record; (b) the recently-required submission of draft labeling and CMC dissolution data for the two new dosage strengths; (c) the recently-required submission of a PAS; (d) the recent prior approval inspection; and (e) the FDA inspector’s direction that Covis be in full compliance with all blend uniformity testing requirements;

(2) Confirm that three-year exclusivity was awarded but never began running for these two dosage strengths that have never been marketed under NDA 20-405, despite their listing in FDA’s Orange Book; and

(3) Confirm that Covis is therefore entitled to a period of three-year marketing exclusivity for the 0.0625 mg and 0.1875 mg dosage strength products that began running upon PAS approval.

In a separate citizen petition – Docket No. FDA-2013-P-1377 – Covis requests that FDA require ANDA sponsors seeking approval of generic LANOXIN Tablets, 0.0625 mg and 0.1875 mg, to meet certain requirements.