Down the Tubes: FDA Settles PREPOPIK NCE Exclusivity Dispute; ANDA Submissions in Unsettled State

Litigation between FDA and Ferring Pharmaceuticals Inc. (“Ferring”) over the availability of 5-year New Chemical Entity (“NCE”) exclusivity for Ferring’s colonoscopy preparation, PREPOPIK (sodium picosulfate, magnesium oxide, and citric acid) for Oral Solution (NDA 202535; approved on July 16, 2012), was recently – and quietly – settled by the parties. Although the terms of the settlement have not yet been made public, we think the settlement will have some pretty significant effects on FDA’s consideration of pending ANDAs for multiple drug products.

As we previously reported, in September 2016, Judge Rudolph Contreras of the U.S. District Court for the District of Columbia issued a Memorandum Opinion granting a Motion for Reconsideration filed by Ferring requesting reconsideration of the DC District Court’s March 2016 ruling that FDA’s pre-October 10, 2014 interpretation of the FDC Act’s NCE exclusivity provisions as applied to a newly approved Fixed-Dose Combination (“FDC”) drug product containing an NCE and a previously approved drug, such as PREPOPIK (see our previous post here), was not arbitrary and capricious. Although Judge Contreras initially backed FDA’s decision to deny NCE exclusivity for PREPOPIK, he reversed course after considering several precedents identified by Ferring in the company’s Motion for Reconsideration, and submitted in response to comments mande by Judge Contreras in his March 2016 ruling that “[i]f there were, in fact, situations in which a drug was eligible for five-year [NCE] exclusivity under the FDA’s prevailing interpretation but failed to receive it because of the order in which it was approved, those circumstances might render the FDA’s policy arbitrary and capricious.”  In addition to PREPOPIK, Ferring identified STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Tablets, NATAZIA (estradiol valerate and estradiol valerate/dienogest) Tablets, ANORO ELLIPTA (umeclidinium bromide; vilanterol trifenatate), and NUVARING (ethinyl estradiol; etonogestrel) as examples that “demonstrate that a single-entity drug substance’s ability to receive five-year exclusivity can turn arbitrarily on the order in which NDAs including that drug substance are approved.”  With those precedents, Judge Contreras had in hand the ammunition necessary to find FDA’s pre-October 2014 interpretation of NCE exclusivity, as applied to PREPOPIK, to be arbitrary and capricious and in violation of the Administrative Procedure Act.

In November 2016, FDA filed a Notice of Appeal with the U.S. Court of Appeals for the District of Columbia Circuit (Case No. 16-5326), and it seemed as though it would be in the hands of the DC Circuit to resolve the issue of NCE eligibility for PREPOPIK, as well as other drugs affected by the outcome of the case, such as Gilead Sciences, Inc.’s (“Gilead’s”) STRIBILD. (Meanwhile, in October 2016, and again in January 2017, Gilead petitioned FDA – see Docket Nos. FDA-2016-P-3312 and FDA-2017-P-1278 – to recognize NCE exclusivity for STRIBILD “and to apply such exclusivity to all subsequently approved drug products that contain any of the new active moieties (elvitegravir and cobicistat) approved” in STRIBILD.)

But then something unexpected happened. . . . On March 14, 2017, FDA filed with the DC Circuit an Unopposed Motion for Voluntary Dismissal.  The DC Circuit dismissed the case in a March 17, 2017 Order, and also issued its Mandate that same day.

Although we have not yet seen anything to indicate why, or under what terms, the case was voluntarily dismissed, we strongly suspect that FDA agreed to award Ferring 5-year NCE exclusivity for PREPOPIK. That also very likely means that any other similarly situated NDA holder will be awarded NCE exclusivity, such as Gilead for STRIBILD.  We should have confirmation soon, and perhaps in April with an update to the Orange Book.

But resetting the exclusivity periods for PREPOPIK, STRIBILD, and other drugs products is going to cause FDA’s Office of Generic Drugs (“OGD”) and affected ANDA applicants some big headaches. ANDAs under review for generic PREPOPIK have been in-house at OGD since May 2014, and ANDAs for generic versions of Gilead’s TYBOST (cobicistat) Tablets (NDA 203094) were first submitted to FDA in December 2015.  FDA even tentatively approved one ANDA – ANDA 205743 – for generic PREPOPIK on November 21, 2016.

Affected ANDA applicants will likely receive correspondence from OGD providing guidance on the path forward in light of FDA’s decision to recognize NCE exclusivity for affected FDC drug products. Presumably, ANDAs will need to be withdrawn and resubmitted to FDA. But will it be a race to resubmission for ANDA Paragraph IV applicants to secure first applicant status (and thus eligibility for 180-day exclusivity)? Or will FDA backdate ANDA submisions to the so-called NCE-1 dates (e.g., July 16, 2016 for generic PREPOPIK, and August 27, 2016 for generic TYBOST) so that previous first-filers don’t lose their place in line? We’ll see.