Eleventh Circuit’s Decision is Not a Catalyst For Change

February 1, 2023By Sara W. Koblitz

FDA has not been shy about its distaste for the Catalyst decision; the Agency has published on its website the litany of problems that arise from it and has sent emails and letters to stakeholders essentially urging them to contact Congress to address the decision.  Indeed, FDA was pushing Congress heavily to legislatively overturn the Catalyst case but ultimately failed to get the provision included in either the User Fee package or FDORA.  So what’s FDA to do when it can’t get the courts or Congress to support its position?  Ignore the decision!  FDA announced in the Federal Register on January 24 that, regardless of the Catalyst decision, the Agency “intends to continue to apply its regulations tying the scope of orphan-drug exclusivity to the uses or indications for which a drug is approved . . .” with the exception of the specific product at issue in the Catalyst case.

In brief, the Eleventh Circuit held in Catalyst that the term “same disease or condition” in the Orphan Drug Exclusivity provisions relates back to the entire disease or condition designated in the Orphan Drug Designation provisions rather than the indication ultimately approved, as FDA had been interpreting the scope of Orphan Drug Exclusivity.  This means that Orphan Drug Exclusivity for an approved designated drug would block the “same drug” for the same disease or condition rather than just the specific indication.  In the case at issue, FDA had approved Catalyst’s Firdapse (amifampridine) with Orphan Drug Exclusivity for the treatment of Lambert-Eaton Myasthenic Syndrome (“LEMS”) but subsequently approved another manufacturer’s amifampridine product for pediatric LEMS during the pendency of the Firdapse exclusivity period.  Catalyst sued, arguing that its Orphan Drug Exclusivity protected the use of amifampridine in the entire LEMS population—adults or pediatrics—under the statute, and the Eleventh Circuit agreed, concluding that the phrase “same disease or condition” in the Orphan Drug Exclusivity statute “unambiguously foreclosed FDA’s interpretation of the provision” as limiting Orphan Drug Exclusivity to the approved indication.  At the Court’s direction, FDA withdrew approval of the amifampridine product for use in pediatric patients but made it quite clear that it did not agree with the Eleventh Circuit’s decision.

The Notice in the Federal Register serves to “address the uncertainty created by the circuit court’s decision in Catalyst.”  For clarity therefore the Agency announced that is has decided to “continue to apply its existing regulations tying orphan-drug exclusivity to the uses or indications for which the orphan drug was approved.”  Even though the Court’s reading of the “unambiguous” statute was quite clear, FDA explained that its decision is appropriate based on the Agency’s reading of the statute—notwithstanding the fact that FDA’s reading of the statute conflicts with the Eleventh Circuit.  So even though the Eleventh Circuit expressly found otherwise, FDA maintains that:

the statutory text does not unambiguously require that orphan-drug exclusivity extend to the entire disease or condition for which a drug received orphan-drug designation if the drug is only approved for some uses within that disease or condition. Further, FDA believes that its statutory interpretation embodied in its regulations best advances the Orphan Drug Act’s purposes, appropriately balancing the need to incentivize the development of drugs for rare diseases and conditions with the need to provide patient access to orphan drugs.

FDA implicitly has told the Eleventh Circuit that the Agency’s interpretation of the Orphan Drug Act trumps the Court’s.

FDA’s announcement in the Federal Register that the Agency will not apply the Eleventh Circuit’s decision beyond amifampridine essentially takes the position that the decision has no precedential value in the view of the Agency.  In other words, FDA is going to technically comply with the Eleventh Circuit decision with respect to amiframpridine but will otherwise pretend that the Eleventh Circuit’s interpretation of the Orphan Drug Exclusivity provisions never happened.  Specifically, FDA said that “the Court ordered FDA to set aside its approval of Jacobus’s drug, and FDA has set aside that approval.”  That’s all the decision called for, and that’s all the Agency intends to do—in FDA’s eyes, it’s done everything the Court asked.

Regardless of the merits of FDA’s position on the Orphan Drug Act provisions, it’s open defiance of the Eleventh Circuit’s interpretation of the Orphan Drug Act is certainly a bold strategy.  But of course it’s not unprecedented.  FDA did the very same thing when the D.C. Circuit held that the plain language of the exclusivity provisions of the Orphan Drug Act requires FDA to recognize Orphan Drug Exclusivity for any drug that FDA has designated and to grant marketing approval without demanding proof of clinical superiority.   There, FDA announced a “Clarification of Policy” that that decision—the Depomed decision—applied only to the drug at issue (Gralise) and that the Agency “intends to continue to apply its existing regulations . . . to require the sponsor of a designated drug that is the ‘same’ as a previously approved drug to demonstrate that its drug is ‘clinically superior’ to that drug upon approval in order for the subsequently approved drug to be eligible for orphan-drug exclusivity.”  In the same way that FDA “doubled-down” on its pre-Depomed approach, it’s doing the same here.

FDA’s Depomed “Clarification of Policy” led to additional lawsuits from Eagle and United Therapeutics challenging FDA’s demand for proof of clinical superiority, effectively requiring the Agency to relitigate the issue until Congress eventually enacted a legislative fix, and we expect the same will happen here.  Obviously, a broader scope of Orphan Drug Exclusivity is a huge boon to an orphan drug sponsor, so it stands to reason that a recipient of Orphan Drug Exclusivity would want to ensure the broadest scope possible and would fight to secure it.  FDA likely anticipates such a lawsuit too, and for that reason, is likely to continue lobbying Congress for a legislative fix.  But until then, we will sit down with some popcorn and watch the orphan drug lawsuits unfold.