By Kurt R. Karst –
Earlier this week, iPR Pharmaceuticals, Inc. (“iPR”), the owner of NDA 021366 for CRESTOR (rosuvastatin calcium) Tablets, 5 mg, 10 mg, 20 mg, and 40 mg, and AstraZeneca Pharmaceuticals LP (“AstraZeneca”), iPR’s agent, filed a Complaint in the U.S. District Court for the District of Columbia seeking to block FDA’s approval of ANDAs for generic CRESTOR Tablets ahead of the July 8th date when many in industry had been anticipating approval (including AstraZeneca, which says that it’s a “foregone conclusion”), The lawsuit, which challenges FDA’s ability to approve ANDAs with labeling that omits information protected by orphan drug exclusivity, comes on the heels of FDA’s May 27, 2016 approval of CRESTOR for the treatment of pediatric patients 7 to 17 years of age with Homozygous Familial Hypercholesterolemia (“HoFH”), a May 31, 2016 Citizen Petition (Docket No. FDA-2016-P-1485) from AstraZeneca and iPR, and a June 24, 2016 letter from AstraZeneca to FDA rejecting the Agency’s award of a period of 3-year new clinical investigation exclusivity for CRESTOR Tablets, 20 mg, for pediatric HoFH (but not, of course, FDA’s award of 7-year orphan drug exclusivity for the same use for all CRESTOR strengths).
As we previously reported, AstraZeneca’s Citizen Petition raises two challenges:
First, carving out AstraZeneca’s protected pediatric HoFH labeling from the labeling of a product marketed under an ANDA or section 505(b)(2) NDA would present substantial safety and efficacy risks. . . .
Second, irrespective of whether a carve out would present a safety risk, FDA lacks legal authority to carve out pediatric labeling protected by orphan drug exclusivity.
AstraZeneca’s Complaint currently concerns the second issue above; however, AstraZeneca notes in the Complaint that the company “intends to bring this separate safety claim before the Court as soon as it is ripe for review.” (That is, if FDA approves ANDAs for generic CRESTOR with labeling that omits information on exclusivity-protected pediatric HoFH.) AstraZeneca also hopes that the legal issue will be resolved before July 8th, stating in the Complaint that the company “will promptly confer to see if Defendants will agree to an expedited briefing schedule that would enable this Court to resolve this case before FDA approves the generic Crestor ANDAs on or about July 8, 2016.” But if FDA is not willing to agree to expedite things, and if FDA is unwilling to provide AstraZeneca with a heads-up on ANDA approval, then “AstraZeneca will have no choice but to file an application for a temporary restraining order to preserve the status quo pending resolution of the merits of AstraZeneca’s claims.” So, things could get ugly in the coming weeks.
The legal issue in the case, says AstraZeneca, is a rub between various laws that establish a “categorical rule” that “[g]eneric drugs must contain all the pediatric information included on the corresponding brand-name drug’s label” (emphasis in original), and certain statutes and regulations – and in particular FDC Act § 505A(o) (a.k.a. the “Anti-Glucophage Provision”; see here and here) – that allow generic drug manufacturers to omit (i.e., “carve out” or “skinny label”) from their labeling certain information protected by patent or non-patent exclusivity. In an April 2015 FDA Letter Decision, which AstraZeneca refers to as the “2015 Interpretation,” FDA laid out a rationale for the approval of ANDAs for generic versions of ABILIFY (aripiprazole) with labeling that omits information concerning pediatric patients and that is protected by orphan drug exclusivity. A court agreed with FDA’s rational in a May 2015 Memorandum Opinion, but AstraZeneca contends that the decision was wrongly decided, and that the 2015 Interpretation is off-base:
FDA’s general carve-out authorities  do not allow a generic sponsor to carve out pediatric labeling protected by orphan drug exclusivity. This conclusion follows from FDA’s interpretation of those authorities in adjudicating the Glucophage ANDAs. It is also supported by the categorical language of FDA’s pediatric-labeling regulations; FDA’s promulgation of those regulations in 1994, after its adoption of the general carve-out regulations; the text, structure, purposes, and history of the FDCA; and Congress’s decision not to include orphan drug exclusivity in section 505A(o).
AstraZeneca alleges that FDA’s 2015 Interpretation violates the Administrative Procedure Act (“APA”) in that it “conflicts with the interpretation of the pediatric-labeling regulations FDA adopted in adjudicating the Glucophage ANDAs; the categorical language of FDA’s pediatric-labeling regulations; and the text, structure, purposes, and history of the FDCA, as amended by the ODA and section 505A(o).” AstraZeneca also alleges that the 2015 Interpretation “departed without explanation from the categorical rule applied by FDA to the Glucophage ANDAs and set forth in FDA’s pediatric-labeling regulations,” which require that certain pediatric information be included in drug product labeling.
AstraZeneca asks that the court, among other things, vacate and set aside FDA’s 2015 Interpretation, and “permanently enjoin FDA from granting approval of any ANDA or other application for a rosuvastatin calcium product prior to expiration of AstraZeneca’s seven-year orphan drug exclusivity period on May 27, 2023 (absent a license from AstraZeneca).”