FDA Sued for Abrogating MAKENA Orphan Drug Exclusivity; Suit Alleges that FDA is Turning a Blind Eye to Compounded 17P and Bowing to Political Pressure

By Kurt R. Karst –      

In a rare lawsuit against FDA involving the Orphan Drug Act of 1983, as amended, K-V Pharmaceutical Company (“KV”) and its wholly-owned subsidiary, Ther-Rx Corporation (“Ther-Rx”), filed a Complaint and a Motion for Temporary Restraining Order and Preliminary Injunction in the U.S. District Court for the District of Columbia last week.  The Plaintiffs are seeking temporary, preliminary, and permanent declaratory and injunctive relief to “restore” Plaintiffs’ orphan drug exclusivity for MAKENA (hydroxyprogesterone caproate) Injection, 250 mg/mL. 

FDA approved MAKENA on February 3, 2011 under NDA No. 021945 “to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.”  Because FDA had previously designated MAKENA (formerly known as GESTIVA) as an orphan drug for the approved indication, the Agency granted KV a period of 7-year orphan drug exclusivity that expires on February 3, 2018.  (On the same day that FDA approved MAKENA, the Agency denied a Citizen Petition – Docket No. FDA-2007-P-0051 – requesting that FDA revoke the orphan drug designation.)  Orphan drug exclusivity prevents FDA from approving another company’s version of the “same drug” for the same disease or condition for 7 years, unless the subsequent drug is different from the approved orphan drug, or because the sponsor of the first approved product either cannot assure the availability of sufficient quantities of the drug or consents to the approval of other applications. 

For several years, hydroxyprogesterone caproate injection, also known as “17p,” has been made available to women at risk of preterm birth by compounding pharmacies that compound the drug.  In some cases, product is reportedly imported into the U.S.  FDA’s policy (see Compliance Policy Guide 460.200), issued in the wake of the U.S. Supreme Court’s April 2002 decision in Thompson v. Western States Medical Center, 535 U.S. 357 (2002) striking down as unconstitutional certain provisions of FDC Act § 503A concerning pharmacy compounding, is generally not to permit pharmacy compounding of drugs that are commercially available and approved by FDA. Nevertheless, in a move that stunned many (including us – see here and here), FDA issued a press release on March 30, 2011 stating, in relevant part, that “[i]n order to support access to this important drug, at this time and under this unique situation, FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products.”  Within hours of FDA issuing its press release (referred to by Plaintiffs as the “Statement”), the Centers for Medicare & Medicaid Services (“CMS”) issued its own statement informing States and Medicaid payers that they “can choose to pay for the extemporaneously compounded hydroxyprogesterone caproate” notwithstanding the availability of MAKENA.  The FDA and CMS statements followed some controversy concerning the price of MAKENA that sparked interest from some members of Congress. 

FDA issued further public statements on MAKENA on November 8, 2011 and June 15, 2012 (here and here), and CMS issued an updated statement on June 15, 2012 in light of some analyses conducted on compounded 17p.  FDA also issued a “Questions and Answers” document on June 29, 2012 discussing the Agency’s risk-based approach to enforcement action against compounding pharmacies and with respect to compounded 17p.  Plaintiffs allege in their Complaint, however, that “[n]one of these statements has announced an intent to take enforcement action against unlawful compounded 17P that is not customized to meet the special needs of individual patients who have the condition for which Makena, a drug that has statutory market exclusivity, is indicated but for whom Makena is medically inappropriate.”  Moreover, Plaintiffs allege that “FDA’s Statement and policy are part of a plan . . . to make unapproved, unlawful, but cheaper, compounded versions of 17P available in the marketplace, despite the statutory market exclusivity that applies to Makena . . . .”

KV and Ther-Rx allege myriad violatations of the law by FDA, including the Administrative Procedure Act, the FDC Act, and the Due Process Clause of the Fifth Amendment to the U.S. Constitution.  Specifically, Plaintiffs allege, among other things, that FDA’s Statement and the policy it sets forth:

• “violate [FDC Act § 527(a)] by effectively nullifying Makena’s statutory seven-year period of market exclusivity by giving de facto approval to compounded versions of 17P that are intended for use to treat the same indication for which Makena is designated as an orphan drug and is approved, and that are not customized to meet the medical needs of individual patients who have the condition for which Makena is indicated but for whom Makena is not medically appropriate”;

• are contrary to the express limitations on compounding set forth in FDC Act § 503A;

• “approve, authorize, invite, encourage, and permit the introduction, and delivery for introduction, into interstate commerce of unapproved new drugs” in violation of FDC Act §§ 505(a) and 301(d), which prohibit the marketing of a new drug without an effective approval; and 

• violate FDC Act § 801(a), which requires FDA to refuse importation of any drug that appears to be unapproved in violation of the new drug approval requirements at FDC Act § 505.  The D.C. District Court recently ruled in Beaty v. FDA that FDC Act § 801(a) requires FDA to deny admission to a drug offered for import that appears to be a adulterated, misbranded, or in violation of Section 355 (see our previous post here).

Judge Amy Berman Jackson, who recently ruled against FDA in a case involving PDUFA user fees (see our previous post here), has been assigned the case.  A Motions Hearing is scheduled for August 7, 2012. 

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