On September 30, 2021, a Washington D.C. circuit appellate court ruled that FDA violated the Orphan Drug Act and unlawfully infringed on Catalyst Pharmaceuticals Inc.’s orphan drug exclusivity period when it approved another company’s drug - the same drug to be used in treating the same disease.
The court ruling in Catalyst v. FDA reversed a previous Florida district court decision which upheld FDA’s claim that the “same disease or condition” language in the Orphan Drug Act is ambiguous and can be interpreted as meaning “same indication or use.”
The appellate court found that FDA’s interpretation of the term was “not in accordance with law, and its approval of Ruzurgi must be set aside.”
In mid-November, Jacobus asked the Eleventh Circuit to reconsider its decision, claiming that the panel erroneously conducted the appeal as a dispute over the ambiguity of the “same disease or condition” language.
Jacobus said it always agreed with Catalyst that their disease and condition – LEMS - are the same, and it never claimed the language was ambiguous. Jacobus claimed the court ignored its actual argument, which was that an exclusivity provision (“coextensive with the scope of the approval”) applies when an orphan drug’s use overlaps but does not fully cover the disease or condition.
Jacobus stated, "The ODA does not unambiguously prohibit the approval of Ruzurgi for a use for which Firdapse was not approved.” [Catalyst Pharmaceuticals Inc. v. Becerra et al.]
Essentially, it claimed the panel created a “straw man,” masking the real issue at hand and preventing Jacobus from a fair defense. Jacobus requested an en banc correction and an affirmation of the district court's summary judgment.
On January 7, the Eleventh Circuit denied Jacobus’ bid in a single-line order, offering no reasoning behind its decision.
FDA Approves Jacobus’ Amifampridine, Overlapping Catalyst’s Exclusivity Period
In November 2009, FDA granted orphan drug designation to Catalyst Pharmaceuticals, Inc.’s Firdapse (amifampridine) for treating the rare, potentially fatal neuromuscular disorder known as Lambert-Eaton myasthenic syndrome (LEMS) – a disorder with an estimated 950 to 1,300 diagnosed U.S. cases.
Nine years later, FDA approved Catalyst’s new drug application for Firdapse (amifampridine) to treat LEMS in adult patients only.
Under the Orphan Drug Act, orphan drug sponsors are granted a seven-year exclusivity period following FDA approval, during which time the FDA cannot approve any subsequent application for "the same drug for the same disease or condition." Catalyst’s seven years of orphan drug exclusivity for Firdapse expires in November 2025.
But in May 2019, FDA approved a pediatric version of amifampridine for LEMS treatment. Jacobus Pharmaceutical Company, Inc. received FDA approval for Ruzurgi to treat LEMS patients ages six through sixteen.
In response, Catalyst sued FDA, arguing that it had violated the Orphan Drug Act’s “same disease or condition” clause in approving Ruzurgi – same drug, same disease.
FDA argued that approving Ruzurgi for pediatric LEMS treatment did not encroach on Catalyst’s Firdapse exclusivity for treatment of adults because the indications differed.
Originally, the Florida district court held that Orphan Drug Act is unclear whether the term “same disease or condition” refers to the drug’s approved use. Therefore, under the Chevron-deference doctrine, FDA could interpret the meaning itself. The court ruled FDA’s interpretation of the phrase as meaning “same indication or use” was reasonable and FDA did not err in approving Ruzurgi.
Appeals Court Says FDA Must “Set Aside” Approval of Ruzurgi
In Catalyst’s appeal, the Eleventh Circuit found that the phrase “same disease or condition” is not ambiguous. It means what it says. All parties involved in the dispute (FDA, Catalyst, Jacobus) agreed that LEMS is the disease and amifampridine is the drug. The court defined the word “same” as “the one under discussion or already referred to,” concluding that pediatric and adult LEMS are the same disease and that FDA cannot interpret “same disease or condition” as meaning “same indication or use.”
“[I]f Congress wanted to make the ‘use or indication’ inquiry relevant to a holder’s market exclusivity for an orphan drug, it could have done so by including such language in § 360cc(a),” the Court stated in its analysis. “The fact that Congress did not include that language counsels against an interpretation that finds an ambiguity in § 360cc(a)’s language.”
The Eleventh Circuit Appeals Court held that the District Court erred in finding the phrase ambiguous, reversing the District Court’s decision, and granting Catalyst’s Motion for Summary Judgment.
“Because it is undisputed that none of the statutory exceptions to Catalyst’s market exclusivity apply, the FDA was prohibited from approving for sale the same drug manufactured by Jacobus Pharmaceutical Company, Inc., to treat the same autoimmune disease during the period of Catalyst’s market exclusivity,” the court concluded. “As a result, the FDA’s agency’s action was arbitrary, capricious, and not in accordance with law, and its approval of Ruzurgi must be set aside.”
In early February, FDA officially withdrew its approval of Jacobus’ amifampridine drug product, Ruzurgi, concluding that – because Ruzurgi is identical to Catalyst’s Firdapse and LEMS is the same for pediatric and adult patients - Jacobus could not demonstrate clinical superiority or any unique feature of Ruzurgi that would justify a pediatric orphan subset.
FDA Disregards Catalyst Decision Moving Forward
On January 24, 2023, FDA commented on its treatment of the seven-year orphan drug exclusivity period moving forward. The agency said it will continue applying the indications and uses in a drug’s approval to the scope of orphan drug exclusivity—in conflict with the court’s ruling in Catalyst.
FDA stated it would not start applying exclusivity as the court recommended in Catalyst because it feels the statutory language does not require orphan-drug exclusivity to cover the entire condition for which a drug received orphan-drug designation when the drug is approved for only some uses in that condition. The agency said that this interpretation supports the intent of the Orphan Drug Act, creating incentive to develop drugs to treat rare diseases, increasing patient access, and prompting drug makers to seek new patient populations.
“These regulations incentivize sponsors to continue to develop a drug for use in all persons affected by a rare disease or condition,” the FDA wrote. “Thus, FDA believes that continued adherence to its validly promulgated regulations will best serve the public health by facilitating patient access to orphan drugs, especially for difficult-to-study patients such as young children.”
In short, FDA will comply with the Eleventh Circuit decision for amiframpridine but will otherwise disregard the Eleventh Circuit’s interpretation of Orphan Drug Exclusivity provisions.
What Catalyst v. FDA Means for Drug Sponsors
The seven-year exclusivity period for FDA-approved orphan drugs is one of the only incentives to develop drugs for rare diseases. Without it, drug makers would pursue more profitable ventures with larger patient populations.
What the Eleventh Circuit’s decision means for the future of orphan drug exclusivity remains to be seen. It may prompt FDA to require NDA and ANDA applicants to narrow their disease descriptions, preventing future applicants from obtaining blanket approval for a rare disease, instead requiring them to specify disease stages or patients who have received certain prior therapies.
This is particularly problematic for rare disease populations, lessening the incentive for drug developers, oversaturating the market, or allowing orphan drug exclusivity for drugs that would otherwise not meet the rare disease requirement.
FDA has been criticized for allowing “serial exclusivity” involving orphan drugs, granting companies multiple consecutive 7-year exclusivity periods for the same drug and same disease with a slightly different disease stage or indication (Ibrutinib, Bevacizumab, Bortezomib).
With the Eleventh Circuit’s decision, NDA and ANDA applicants could start challenging these serial approvals, claiming FDA is unlawfully granting subsequent approval for the same drug and same disease and therefore allowing a single company to corner the market and block cheaper generics.