Yet Another Petition to FDA Says: “Gimme My 5-Year NCE Exclusivity!” But What’s it to Ya?

July 16, 2014

By Kurt R. Karst –      

Our FDA Citizen Petition Tracker is littered with petitions and petitions for reconsideration submitted to FDA over the past 18 months requesting that the Agency recognize a period of 5-year New Chemical Entity (“NCE”) exclusivity for certain Fixed-Dose Combination Drugs (“FDCs”) the Agency approved before announcing in February 2014 in a draft guidance document (and in a consolidated citizen petition decision) that FDA planned to change (but only prospectively for FDCs approved after the guidance is finalized) its interpretation of the FDC Act’s NCE exclusivity provisions to award 5-year exclusivity for a newly approved FDC containing an NCE and a previously approved drug (see our previous posts here, here, and here).  The period to comment on the draft guidance expired months ago, and there has been no indication as to when it might be finalized.  This, of course, raises the possibility that more companies will petition FDA as NDAs for FDCs are approved in the interim period.

The latest entrant to the “NCE for FDC Club” is Pfizer Inc. (“Pfizer”).  In a May 30, 2014 petition (Docket No. FDA-2014-P-0737) that was only recently made public on the federal government’s docketing system website (, Pfizer says FDA erred in not granting NCE exclusivity with respect to Pfizer subsidiary Wyeth Pharmaceuticals, Inc.’s DUAVEE (conjugated estrogens/bazedoxifene) Tablets on the basis that FDA never before approved a drug product under FDC Act § 505 containing bazedoxifene as an active moiety.  FDA approved DUAVEE on October 3, 2013 under NDA No. 022247 for use in women with a uterus for treatment of moderate to severe vasomotor symptoms associated with menopause and prevention of postmenopausal osteoporosis, for the treatment of moderate to severe vulvar and vaginal atrophy associated with menopause, for the treatment of moderate to severe vasomotor symptoms associated with menopause, and for prevention of postmenopausal osteoporosis.  Six months later, in the March 2014 Orange Book Cumulative Supplement (published in mid-April), FDA finally made public the Agency’s decision to – not unexpectedly – award a period of 3-year new clinical investigation exclusivity.  But that doesn’t mean the decision is correct, says Pfizer. 

Similar to other “NCE for FDC Club” petitioners who have challenged FDA’s basis for denying NCE exclusivity, Pfizer argues that none of the reasons FDA articulated in the February 2014 Consolitated Petition Decision apply in this case.  Briefly, FDA said that the Agency would not immediately or retroactively apply its new interpretation of the statute’s NCE exclusivity provisions for several reasons:

First, although the relevant statutory and regulatory provisions are ambiguous, our existing interpretation of these provisions is longstanding and has been consistently applied in many prior cases presenting similar facts.  Second, the new interpretation we are proposing represents a departure from our past interpretation, and we wish to avoid any unnecessary disruption to regulated industry.  Third, if the new interpretation were to be applied to products for which ANDAs already have been filed, it could impose a burden on the ANDA sponsors, who relied on our existing interpretation in filing their applications.

In addition, we do not believe that applying our new interpretation to the Petitioners’ products would advance the goals of the Hatch-Waxman Amendments. . . . Recognizing additional exclusivity in this case is not necessary to encourage the development of novel drugs.  We believe that changing our interpretation going forward will foster Congress’s goal of encouraging the development and approval of novel drugs.  (Emphasis in original.)  

According to Pfizer:

None of the concerns articulated by FDA support denial of 5-year exclusivity for bazedoxifene.  The general presumption is that an agency will apply a new statutory interpretation adopted in the course of an administrative adjudication in that proceeding, and all subsequent adjudications.  There is no reason to depart from that general practice here.  Furthermore, none of the concerns about “retroactive” regulatory changes that might call for a different effective date are apposite here.  Certainly, FDA’s concerns about disrupting industry and burdening ANDA sponsors do not apply in the case of bazedoxifene.  Indeed, those concerns do not apply to any FDC drug products containing at least one new active moiety for which no ANDA was filed prior to the date of issuance of the Consolidated Response.  And, even as to ANDAs filed before the Consolidated Response, there is no impermissible retroactive effect on the ANDA applicants of FDA immediately applying its new policy to all cases adjudicated from that date forward, such as bazedoxifene.

There is no indication that an ANDA has been submitted to FDA for a generic version of DUAVEE.  In fact, FDA has not approved an ANDA for conjugated estrogens.  Way back in May 1997, FDA ruled in the context of PREMARIN (conjugated estrogens) Tablets, that because PREMARIN “is not adequately characterized at this time, the active ingredients of Premarin cannot now be definitively identified,” and that “[u]ntil the active ingredients are sufficiently defined, a synthetic generic version of Premarin cannot be approved.”  Instead, companies have generally pursued approval of 505(b)(2) NDAs – e.g., CENESTIN (synthetic conjugated estrogens, A) Tablets. 

Whether today, 17 years after FDA’s PREMARIN decision, FDA is willing to entertain approval of an ANDA for conjugated estrogens remains to be seen.  FDA has accepted ANDAs for conjugated estrogen drugs, as the Agency’s ANDA Paragraph IV List indicates that an ANDA was submitted for generic PREMARIN prior to March 2, 2004, and that ANDAs for generic CENESTIN were submitted in November 2008 and March 2009.  But years after these ANDA acceptances, there’s still not an approval. 

That raises the question of why NCE exclusivity for DUAVEE – and specifically for the bazedoxifene moiety – is so important to Pfizer.  An ANDA for a generic version of a drug product containing conjugated estrogens will likely be very difficult to push through FDA’s Office of Generic Drugs.  A 505(b)(2) NDA for the combination is perhaps more likely, though there is no mention of that approval route in the DUAVEE petition.  So that leaves us with bazedoxifene.  That moiety is currently under investigation for other uses according to and other reports.  A grant of 5-year NCE exclusivity with respect to bazedoxifene would help extend the lifecycle of that drug if there are follow-on NDA approvals in the coming years.