21 U.S.C. § 360aa et seq., as drafted before 2017 amendments)Eagle Pharms. Inc. v. Azar, No. 18-5207 (D.C. Cir., Mar. 13, 2020).See 21 U.S.C. § 360cc(c).Spectrum Pharms., Inc. v. Burwell, 824 F.3d 1062, 1064 (D.C. Cir. 2016).

FDA rightly concluded that approval of Ruzurgi for treatment of LEMS in adults was blocked by Firdapse’s orphan exclusivity.Nevertheless, in May 2019 – during the 7-year exclusivity for Catalyst’s Firdapse – FDA approved Ruzurgi for the treatment of LEMS in pediatric patients 6 to less than 17 years of age, despite the limited pediatric data in the Ruzurgi NDA. Consistent with its regulations, FDA concluded that the scope of orphan exclusivity for Firdapse was limited to its approved use in adults, and the approval of Ruzurgi for pediatric patients was for a different “indication or use.”Catalyst sued FDA in federal district court, and Jacobus intervened in support of FDA. Catalyst alleged that the ODA prohibited FDA from approving Ruzurgi because it is the “same drug” as Firdapse and treats the “same disease or condition” as Firdapse, as defined by 21 USC 360cc. Specifically, 360cc(a) states that:…for a drug designated under section 360bb of this title for a rare disease or condition, the Secretary may not approve another application […] for the same drug for the same disease or condition for a person who is not the holder of such approved application or of such license until the expiration of seven years from the date of the approval of the approved application or the issuance of the license.

2See Presidential Statement on Signing the Orphan Drug Act, 1 PUB. PAPERS 9 (Jan. 4, 1983).3See 21 U.S.C. §§ 360aa-360ee (2018).4Seeid.5See U.S. Dept. of Health & Human Servs., Off. of Inspector Gen., The Orphan Drug Act: Implementation and Impact, OEI-09-00-00380 (2001).6See 21 U.S.C. § 360cc(a).7Seeid. § 360bb(a)(2).8Seeid.

608. TECHNICAL CORRECTIONS.Section 527 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360cc) is amended—(1) in subsection (a), in the matter following paragraph (2), by striking “such drug for such disease or condition” and inserting “the same drug for the same disease or condition”;(2) in subsection (b)—(A) in the matter preceding paragraph (1), by striking “If an application” and all that follows through “such license if” and inserting “During the 7-year period described in subsection (a) for an approved application under section 505 or license under section 351 of the Public Health Service Act, the Secretary may approve an application or issue a license for a drug that is otherwise the same, as determined by the Secretary, as the already approved drug for the same rare disease or condition if”;(B) in paragraph (1), by striking “notice” and all that follows through “assure” and inserting “of exclusive approval or licensure notice and opportunity for the submission of views, that during such period the holder of the exclusive approval or licensure cannot ensure”; and(C) in

This Bulletin will summarize many of the highlights of FDA’s decision and offer our own observations. Previous AGG Bulletins have described orphan drug laws in detail.2BackgroundThe main issue in the recent decision was whether the orphan drug exclusivity (“ODE”) for a calcium, magnesium, potassium, and sodium oxybates drug product blocked the approval of another new drug application (“NDA”) for a sodium oxybate for extended-release oral suspension product for the treatment of cataplexy or excessive daytime sleepiness (“EDS”) in adults with narcolepsy.The first product received ODE for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. The sponsor demonstrated, at the time of approval, it was clinically superior to (yet) another product, which was previously approved for the same indication. According to section 527(a) of the Federal Food, Drug, and Cosmetic Act (“FDC Act”), (21 U.S.C. § 360cc), an ODE prevents FDA from approving a new drug product that is the “same drug” as another for the same use or indication until the first exclusivity ends.By regulation (21 C.F.R. § 316.3), a drug is the “same drug” if it contains the same active moiety for the same use or indication, unless the new drug product is clinically superior to the first with ODE.In this case, FDA found that the second drug was clinically superior to the first. Therefore, it was not the “same drug” within the meaning of the law.In addition, the agency concluded that the second product was eligible for its own ODE term because ODE can only block approval of “same drugs” for the same uses or indications. According to section 527(c)(1) of the FDC Act, if FDA has previously approved a drug that is otherwise the same drug for the same use or indication, the subsequent drug may be eligible for its own term of ODE if the sponsor demonstrates that its product is clinically superior to every previously approved dru

le for a subsequent effective approval for the application under subclause (III) of subparagraph (B)(iv) unless, in addition to meeting each of the conditions in such subclause (III), it submits a certification to its abbreviated new drug application that an event that could not have been reasonably foreseen by the applicant prevented it from commencing commercial marketing and that it has fully resolved this issue. The applicant shall submit notification to the abbreviated new drug application confirming that such applicant has commenced commercial marketing of the drug not later than one business day after commencing such marketing.The applicability of these provisions is limited to applications under Section 505(j) after enactment of the legislation.3.The Retaining Access and Restoring Exclusivity (RARE) Act (S. 1214)This bill was introduced by Sen. Tammy Baldwin (D-WI) and co-sponsored by Sen. Mike Braun (R-IN). The bill would amend Section 527 of the Food, Drug, and Cosmetic Act (21 U.S.C. § 360cc) to close a loophole in orphan drug designation, regarding applicants developing newer versions of an orphan drug and getting undeserved exclusivity to such drugs. The exclusivity provision is amended to be limited to "the same approved use or indication within such rare disease or condition" and a new subsection added that "defines the term 'approved use or indication' [to mean] the use or indication approved under section 505 of this Act or licensed under section 351 of the Public Health Service Act for a drug designated under section 526 for a rare disease or condition." These limitations shall apply to any drug designated as an orphan drug "regardless of the date on which the drug was so designated" or approved.The bill was motivated, according to Sen. Baldwin, by a decision in the 11th Circuit, Catalyst Pharms., Inc. v. Becerra, that provides incentives for pharmaceutical companies to seek the broadest orphan drug designation they can obtain but to pursue narrow clinical studies

On January 24, 2023, FDA published a notice in the Federal Register entitled, “Clarification of Orphan-Drug Exclusivity Following Catalyst Pharms., Inc. v. Becerra.” In brief, the Catalyst decision by the 11th Circuit Court of Appeals concerned FDA’s application of the Orphan Drug Act (21 USC 360cc(a)), and in particular the extent of the 7-year orphan drug market exclusivity (ODE) provided with an orphan drug’s approval. The ODE, per the Orphan Drug Act prevents FDA from approving another applicant’s same drug for “the same disease or condition.”Catalyst arose out of FDA’s approval of a drug for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) (an orphan disease) in children to a Catalyst competitor, despite FDA having previously approved and awarded ODE to Catalyst’s same drug product for LEMS in adults. Catalyst’s ODE was unexpired at the time that FDA approved the competitor’s product. FDA based its approval decision on FDA’s long-asserted position that ODE only applies to the specific indication that FDA ultimately approves. Therefore, FDA claimed its approval and award of ODE to a product that is indicated for use in adults does not preclude FDA from approving the same drug for the same use in children.The Catalyst court disagreed, holding that “the phrase ‘same dise

ncy’s position (and hopefully the logjam of orphan drug exclusivity decisions will now subside), sponsors seeking to challenge the agency’s interpretation can attempt to use the Catalyst playbook – at least until a(nother) legislative fix comes along to support FDA’s long-held interpretation.Law clerkMadelon Bird also contributed to this alert.Notes76 Fed. Reg. 202, 64871 (October 19, 2011).Catalyst Pharms., Inc. v. Becerra, No. 20-13922, DC Docket No. 1:19-cv-22425-BB, 9 (11th Cir. 2021); see also 21 USC § 355(b).Id.Id; see also 21 USC § 355(b).See e.g., Eagle Pharm. v. Azar, 952 F.3d 323 (DC Cir. 2020). While the Eagle case was pending, Congress amended the Orphan Drug Act to allow the FDA to impose a clinical superiority requirement when determining whether a drug will obtain orphan drug exclusivity, thus resolving the issue in the case as of the date of the revised legislation. See the FDA Reauthorization Act of 2017, Pub. L. No. 115-52, § 607(a), 131 Stat. 1005, 1049-50 (amending 21 USC § 360cc). The Eagle case proceeded, however, as the appellant in that case was subject to the earlier version of the law, and thus a case or controversy remained for the court to decide.Catalyst Pharms., Inc. v. Becerra, No. 20-13922, DC Docket No. 1:19-cv-22425-BB, 9 (11th Cir. 2021).Id. at 7.[View source.]

2821 U.S.C. § 384e(a)(1).29See U.S. Food & Drug Admin., Mutual Recognition Agreement / Frequently Asked Questions and Answers” (Jan. 2021), available athttps://www.fda.gov/media/103391/download.30Section 526(a)(1) of the FD&C Act (21 U.S.C. § 360bb(a)(1)).31Section 527(a) of the FD&C Act (21 U.S.C. § 360cc(a)).32SeeDepomed, Inc. v. U.S. Dep’t of Health & Human Servs., 66 F. Supp. 3d 217 (D.D.C. 2014).33In Eagle Pharms., Inc. v. Azar, 952 F.3d 323 (D.C. Cir. 2020), the court held that the language in section 527 (prior to the passage of FDARA) foreclosed FDA’s conditioning eligibility for orphan drug exclusivity on a demonstration of clinical superiority. See alsoDepomed, 66 F. Supp. 3d 217.34See section 201(g) and (h) of the FD&C Act (21 U.S.C. § 321(g) and (h)).

6 Id. at 159. 7 Drug Price Competition and Patent Term Restoration Act (codified at 21 U.S.C. §§ 355 & 360cc). 8 AB 824 § 134002(a)(3)(A).