FDA Oops: Two Orphan Drugs Approved for Same Disease or Condition

Jason Velligan

Associate Editor

Loyola University School of Law, JD 2024

An orphan drug treats a rare disease or condition that occurs so infrequently in the United States that there is no reasonable expectation that the cost of making the drug will ever be recovered by the manufacturer. The Orphan Drug Act of 1983 incentivizes pharmaceutical manufacturers to investigate and develop drugs for rare diseases with a low probability of profitability. Orphan drugs have been approved and used to treat various cancers, Huntington’s disease, Fragile X syndrome, pulmonary fibrosis, myelomas, carcinomas, and other rare and unfortunate ailments that impact people’s lives. According to the National Organization for Rare Disorders, the number of approved drugs for treating rare diseases soared from 38 drugs before the act to 6,583 orphan-drug designations by the Food & Drug Administration (FDA) today. Undoubtedly, the Orphan Drug Act has had a positive impact on both patients suffering from rare conditions and the manufacturers that utilized the law.

Orphan Drug Approval

A pharmaceutical company seeking orphan drug status must file a request with the FDA. If granted, the company gains financial incentives and tax benefits for drug development. Following successful clinical trials that demonstrate the drug’s safety and efficacy, the manufacturer must then file a New Drug Application (NDA) with the FDA, just as they would for any other drug. If the FDA recognizes exclusive approval of the orphan drug, then the manufacturer receives a seven-year term of exclusive approval. The manufacturer has market exclusivity during this seven-year period, and the FDA may not approve or license another manufacturer to produce the same drug for the same disease or condition.

Dueling Orphan Drug Approvals

In Catalyst Pharma. v. Becerra and Jacobus Pharma (September 30, 2021), the 11th Circuit considered whether the term “same disease or condition” contained in the Orphan Drug Act is ambiguous. Jacobus Pharmaceutical Company developed a drug called Ruzurgi (amifampridine) to treat a rare disease called Lambert-Eaton Myasthenic Syndrome (LEMS). The FDA granted it orphan drug status in 1990, and Mayo Clinic doctors have been prescribing it since 1993 under the FDA’s compassionate use program. The FDA rejected Jacobus’ August 2017 NDA for Ruzurgi.

Catalyst Pharmaceuticals developed a drug called Firdapse (amifampridine phosphate) to treat LEMS, and the FDA designated it as an orphan drug in 2009. The FDA rejected Catalyst’s first NDA for Firdapse in December 2015. The FDA approved Catalyst’s March 2018 NDA for Firdapse on November 28, 2018, for treatment in adults for LEMS and granted exclusivity through November 28, 2025. The FDA approved Jacobus’ June 2018 for Ruzurgi on May 6, 2019, for LEMS “in patients 6 to less than 17 years of age.”

The 11th Circuit found that the Orphan Drug Act’s providing exclusivity for “the same disease and condition” is unambiguous. This led to the nullification of the FDA’s approval of Jacobus’ Ruzurgi. Manufacturers provide clinical data through NDAs to demonstrate a drug’s effectiveness for use in specific populations. Just before the 11th Circuit’s decision, Catalyst finished its pediatric study in April 2021, submitted a supplemental NDA for Firdapse, and obtained approval for use in pediatric populations. This enabled Catalyst to first secure approval for adult use and then file suit against Becerra, the Secretary of Health and Human Services, after the FDA approved Ruzurgi for pediatric populations.

The problem here is that Jacobus’ Ruzurgi was already designated as an orphan drug (1990) and already being used in pediatric patients through the FDA compassionate use program at the Mayo Clinic (1993). In contrast, Catalyst’s Firdapse was designated as an orphan drug (2009) 19 years after Ruzurgi. Jacobus followed rules, and in the end, they were correctly, even though unfairly, prohibited from selling the Ruzurgi. The text of the Orphan Drug Act is unequivocal as to “same disease or condition” and makes no distinction as the indicated population.

FDA Rule After Catalyst

The FDA subsequently revoked the approval of Jacobus’ Ruzurgi. However, on January 24, 2023, the FDA published a rule “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.” The same regulations that caused the Catalyst debacle are still in effect. However, maybe the FDA will look closely at what orphan drugs are under development and being developed before issuing orphan drug designations or NDAs. Since the Supreme Court denied review of the Catalyst decision, a circuit split on this issue in the future would create a case ripe for review.