How is orphan drug exclusivity affected when the FDA-approved use for an orphan drug is arguably narrower than the treatment of the rare disease it was designated for?

By way of background, a sponsor can obtain orphan drug exclusivity when the FDA approves an application for a drug that has first been designated under 21 U.S.C. § 360bb of the Orphan Drug Act (ODA) for a “rare disease or condition.”  Id. § 360cc(a).  Except in any of three statutorily prescribed circumstances (§§ 360cc(b), (c)), the FDA cannot approve another application for the “same drug” for “the same disease or condition” for seven years after the first approval.

In Catalyst Pharms., the 11th Circuit weighed in on the scope of the “disease or condition” that underlies this exclusivity.  See Catalyst Pharms. v. Becerra, No. 20-13922 (11th Cir. Sept. 30, 2021).  Under its interpretation, the race to orphan drug approval may result in winner-takes-all exclusivity even for a limited approved indication, if the initial designation is broad.

Race to Approve Amifampridine for LEMS Therapy

As discussed in the 11th Circuit’s opinion, this dispute arose from two pharmaceutical companies’—Jacobus and Catalyst—efforts to obtain approval of their respective amifampridine products for the treatment of Lambert-Eaton Myasthenic Syndrome (LEMS), a rare autoimmune disease.

Amifampridine was first designated as an orphan drug for LEMS treatment in 1990—for Jacobus’ product Ruzurgi®.  Ruzurgi® was not FDA-approved at that time, and Jacobus continued to test it over the next several decades.

In the interim, Catalyst developed its own amifampridine product, Firdapse® and the FDA in 2009 also designated that amifampridine product as an orphan drug for LEMS treatment.  Catalyst filed its NDA several years later and ultimately received approval in November 2018 for the treatment of LEMS “in adults.”

Around that time, Jacobus began pursuing an NDA for Ruzurgi®.  Its labeling indicated that clinical studies supported Ruzurgi®’s use in pediatric patients—although, according to Catalyst, Jacobus only conducted trials in adults and its limited pediatric safety data came from compassionate use studies.

Recognizing that Catalyst held exclusivity for LEMS treatment in adults, the FDA divided Jacobus’s NDA into two parts—for the treatment of pediatric and adult patients—“to allow for independent action” for these two indications, on the grounds that treatment of pediatric patients was a different “indication or use” than approved for Firdapse®.  Ruzurgi® was approved for use in pediatric patients in May 2019.

Under the ODA, the “Same Disease or Condition” Relates to the Designation, Not an Approved Use

Catalyst challenged Ruzurgi®’s approval as a violation of the Administrative Procedure Act.  The district court concluded that the ODA’s term “the same disease or condition” was ambiguous because, the court reasoned, it was unclear whether this term referred to the “use” ultimately approved by the FDA to treat a disease (e.g., LEMS in a patient subpopulation) or condition pursuant to § 355 or to the “rare disease or condition” designated pursuant to § 360bb (LEMS).  Finding that either interpretation was reasonable, the district court deferred to the FDA’s approach pursuant to the Chevron deference standard.

On appeal, the 11th Circuit’s analysis focused on the same issue.

“Same Disease or Condition” Is Unambiguous.  Noting (among other things) that Congress had not included § 355’s “use or indication” language in § 360cc(a), the 11th Circuit held that the disease referred to in § 360cc(a)’s “same disease or condition” is the “rare disease or condition” for which the drug was designated under § 360bb.

Similarly, the court also held that § 360cc(a)’s “same disease or condition” term is not ambiguous, finding that it “plainly refers back to” § 360bb’s “rare disease or condition” term.

Ruzurgi®’s Approval Was Arbitrary and Capricious.  Because Catalyst and Jacobus’s drugs were (undisputedly) the “same drug” (amifampridine) for the “same disease” (LEMS), the 11th Circuit found that § 360cc prohibited the approval of Ruzurgi® to treat LEMS during Catalyst’s exclusivity period.  Accordingly, it reversed and directed entry of summary judgment for Catalyst.

Notably, in rendering this decision, the court pointed to various items of undisputed record evidence.  It observed that “LEMS is the same disease in all people suffering from it, regardless of their age.”  Additionally, “there is nothing in the record to suggest that the FDA qualified its § 360bb designation with an age-restriction or that the designation of Firdapse applied to anything other than LEMS for all people suffering from the disease.”

The court also noted that, because none of the three statutory exemptions to § 360cc(a) exclusivity applied in this case, it was “irrelevant” that Ruzurgi®’s NDA addressed a subpopulation of LEMS patients.

Takeaways for Pharmaceutical Companies

If a sponsor pursues orphan drug exclusivity, it may be incentivized under Catalyst Pharms. to seek the broadest possible § 360bb designation and then pursue approval—even for a narrow indication—quickly.

The case highlights various risks for failure to do so.  While the sponsor is developing its product, for example, competitors may obtain orphan drug designations for the “same drug.”  The first company to receive any form of approval may win the full scope of exclusivity.

As others have recognized, however, orphan drug clinical trials are complicated by numerous practical considerations, including an incomplete understanding of the disease (for which symptoms may vary), the limited number of medical specialists, and difficulties recruiting the small (and diverse) patient population.

If the sponsor loses the race for first approval, however, it may have other options.  Catalyst Pharms. suggests that a sponsor who is behind in conducting its clinical trials should be mindful of the statutory exemptions to § 360cc(a) exclusivity—particularly, whether it can position its drug under § 360cc(c)(1) as clinically superior to the competition.

We will continue to monitor this area and report on further developments.

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Photo of Siegmund Y. Gutman Siegmund Y. Gutman

Siegmund (“Sige”) Gutman is chair of the Life Sciences Patent Practice, a partner in the Litigation Department, and a member of the Patent Law and Intellectual Property Groups.

Sige is an accomplished patent litigator, frequently representing clients before trial and appellate courts, as…

Siegmund (“Sige”) Gutman is chair of the Life Sciences Patent Practice, a partner in the Litigation Department, and a member of the Patent Law and Intellectual Property Groups.

Sige is an accomplished patent litigator, frequently representing clients before trial and appellate courts, as well as arbitration panels. In the life sciences area, his practice focuses on developing and executing market exclusivity and freedom-to-operate strategies, including patent office and FDA regulatory strategies, for leading biologics, pharmaceutical, biotechnology, and medical device clients. He has extensive experience successfully litigating biologic drug patent and Hatch-Waxman cases, and has frequently spoken and written about issues relating to biosimilars and generic drugs. Sige’s background combines a graduate degree in molecular and cell biology and biophysical chemistry with more than 20 years of industry experience, including serving as senior patent litigation counsel for Amgen, the world’s largest biotechnology company.

He advises clients on patent matters involving a wide range of technologies, including therapeutic proteins such as monoclonal antibodies, antibody-drug conjugates, nucleic acids, gene therapy, stem cells, expression systems, screening methodologies, purification processes, DNA microarrays, small molecules and polymer chemistry.

Sige also has extensive experience in inter-partes patent office actions, including oppositions, and providing strategic patent counseling, including addressing product life cycle management and patent portfolio development issues, as well as preparing third-party patent landscape analyses.

Prior to joining Proskauer, Sige was a partner at another Am Law 100 firm.

While in graduate school, Sige worked on elucidating the 3-D structure of an auto-catalytic RNA using molecular biological, biochemical and biophysical techniques. He also previously worked for a major manufacturer of photocopiers and printers, where he helped develop novel color toner particles using electrochemical, photochemical and polymer chemical techniques.