More than a year has passed since the US Court of Appeals for the Eleventh Circuit’s decision in Catalyst Pharms., Inc. v. Becerra struck down the US Food and Drug Administration’s (FDA) indication-specific interpretation of orphan drug exclusivity (ODE).1 In response to that September 2021 decision, FDA’s Office of Orphan Products Development (OOPD) has deferred all of its pending orphan exclusivity determinations. In fact, OOPD has not publicly recognized orphan exclusivity for any product approved since November 2021. Rather than recognize a broad, disease-specific scope of orphan exclusivity consistent with the Eleventh Circuit’s opinion, the agency appears to be waiting for a legislative fix to effectively overrule the Catalyst decision. The status of that legislative fix is in jeopardy, however, in light of the recent passage2 of a “clean” version of the FDA user fee reauthorization provisions—without any changes to the Orphan Drug Act. As a result, sponsors remain in the dark about the impact of the court decision, and FDA has given little indication how the agency intends to proceed.
The Catalyst Decision
Briefly, the Catalyst decision held that FDA’s indication-specific interpretation of the scope of ODE was incompatible with the Orphan Drug Act’s exclusivity provision, which describes a “rare disease or condition.” Under FDA’s historical approach, which had been codified in agency regulations since 2013, a drug product approved for an “indication or use” that is narrower than the “rare disease or condition” for which the orphan designation was granted would obtain exclusivity only for the approved indication or use. However, the Eleventh Circuit held in Catalyst that the scope of exclusivity was as broad as the rare disease or condition for which designation was granted, even if a drug product’s approval was for a narrower indication. In the context of the Catalyst case, the court thus concluded that the orphan exclusivity for Catalyst’s Firdapse (amifampridine phosphate) blocked approval of Jacobus Pharmaceutical Co.’s (Jacobus’s) competitor product, Ruzurgi (amifampridine), for a different indication.3
The Aftermath, Part 1: Catalyst and Jacobus Settle Their Dispute, Leaving Firdapse the Sole Product on the Market
Following the Eleventh Circuit decision, intervenor-defendant Jacobus initially submitted a petition for a writ of certiorari to the Supreme Court in hopes of overturning the appellate court’s decision. FDA did not join or otherwise seek further review. Before the Supreme Court ruled on the Jacobus petition, however, the issue became moot—at least with respect to the two amifampridine products. In the context of related patent litigation brought by Catalyst against Jacobus, the two companies announced a settlement in July 2022, whereby Jacobus agreed to withdraw its petition to the Supreme Court and Catalyst dismissed its patent infringement claims and acquired rights to distribute Jacobus’s Ruzurgi in the US.4
What is more, in late September 2022, FDA approved a supplement to the Firdapse NDA for use in pediatric patients older than 6 years of age. As a result, the outcome that FDA appears to have sought to avoid—a single approved amifampridine product on the market—remains the status quo, at least until the expiration of the seven-year orphan exclusivity period for Catalyst’s Firdapse in November 2025.
The Aftermath, Part II: What About All the Other Orphan Drug Products?
The impact of the Catalyst decision on FDA and the rare disease industry has been significant. As noted in our previous Legal Update, the scope of orphan exclusivity for existing products remains unclear. For products approved since the Catalyst decision, the situation is even worse. These sponsors cannot even be certain that their orphan-designated products will be protected by orphan exclusivity, because FDA’s OOPD has effectively stopped making exclusivity determinations since late 2021. The agency appears to be seeking to avoid having to recognize an orphan exclusivity broader than a product’s approved use, as the Catalyst decision would seem to require of FDA.
Key to the agency’s inaction had been the possibility—or even expectation—that the user fee reauthorization legislation would include a provision effectively overruling Catalyst and codifying FDA’s orphan exclusivity regulation. Indeed, the user fee bills initially released by both the House and the Senate contained provisions amending the statutory exclusivity provision to narrow the scope of ODE to the “approved use or indication.”5 Both bills also included language designed to have the new provisions applied retroactively:
(b) Application of Amendments. The amendments made by subsection (a) shall apply with respect to any drug designated under section 526 of the Federal Food, Drug, and Cosmetic Act, regardless of the date on which the drug was so designated, and regardless of the date on which the drug was approved under section 505 of such Act or licensed under section 351 of the Public Health Service Act.6
Unfortunately for FDA, those proposed amendments were dropped from the “clean” user fee reauthorization provisions included in the legislation passed in late September. Amidst reports that both houses of Congress will in the coming months revisit proposals dropped from the user fee bills, FDA appears poised to continue waiting on Congress to resolve the agency’s conundrum.
So where does that leave rare disease sponsors with investigational or approved drug products? In limbo, unfortunately. Given OOPD’s inaction, there are (as of the date of publication) more than 60 products approved for more than 70 orphan-designated indications for which OOPD has issued no public orphan exclusivity determination. For more than a year, no “ODE” codes have been added to the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable orphan designation database.
OOPD has made one concession to sponsors: the OOPD database now includes a “TBD” notation for those products whose eligibility for orphan drug exclusivity has not been determined. (However, the “TBD” notation only appears when query results are listed in the “condensed” format but not if results are listed in the “detailed” format or in an Excel file.)
Our Take, for FDA
We urge FDA to take a more nuanced approach. For products approved since the Catalyst decision was finalized, OOPD should make a final determination about whether the product has earned ODE and make that determination public by noting the exclusivity in the Orange Book (with an “ODE” code) and by listing a date in the Exclusivity End Date field in the orphan designation database, i.e., the date that is seven years after the relevant approval. Doing so would provide sponsors greater clarity, without forcing the agency to address the scope of the ODE unless and until absolutely necessary—or the above-noted legislative fix arrives. In the meantime, sponsors are left in limbo, without the ability to provide updates to the public and the investment community about the exclusivity for their orphan-designated products.
The agency could also consider opening a public docket to solicit stakeholder feedback on proposed resolutions, should a legislative fix not arrive soon.
Our Take, for Sponsors
For sponsors of recently approved orphan products, who are unlikely to face competitor applications in the short term, further patience will likely be required as the agency waits to see whether the legislative fix will arrive. In the meantime, we recommend that sponsors carefully assess whether a competitor is likely to seek approval for the indication or use whose orphan exclusivity has not yet been recognized by FDA. In that situation, consideration should be given to a more assertive approach, including petitioning FDA to award the orphan exclusivity or preparing for potential litigation prior to a competitor approval.
3 FDA initially granted final approval to Jacobus for “treatment of Lambert-Eaton myasthenic syndrome (LEMS) in pediatric patients 6 to less than 17 years of age” on the basis that Firdapse’s ODE was limited to its approved use, “treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults.”
4 See Catalyst Press Release, Catalyst Pharmaceuticals Announces Settlement of U.S. Patent Litigation and Resolution of Litigation Challenging Ruzurgi® Approval with Jacobus Pharmaceutical, (July 12, 2022), available at https://ir.catalystpharma.com/news-releases/news-release-details/catalyst-pharmaceuticals-announces-settlement-us-patent.