Novel Drug Approvals By the U.S. Food and Drug Administration in Rare Diseases: Findings from 2020–2023

OBJECTIVES: U.S. Food and Drug Administration (USFDA’s) Centre for Drug Evaluation and Research approves several novel drugs every year, spanning a wide range of rare diseases to promote innovations among pharmaceutical companies and provide safe and effective treatment options to patients. The objective of this study was to systematically review the novel drugs approvals (NDAs) by USFDA for rare diseases.

METHODS: We retrieved NDAs listed from the USFDA drug database, and their respective labels published from January 2020 to November 2023. Screening and analysis were performed on the approved drugs which included estimation of total number, indication type, category of approval, regulatory pathways followed, and pivotal trial endpoints including patient-reported outcomes (PROs).

RESULTS: A total of 192 NDAs were identified, out of which approximately half (55.7%) of the NDAs were pertaining to rare diseases. Three foremost indications including oncology (22.9%), neurology (20.6%), and endocrinology (9.5%) constituted approximately 50% of the NDAs. Majority (96.3%) of the drugs received orphan drug designation, and approximately half (53.3%) of approved drugs were first-in-class. Many novel drugs were assessed through more than one approval processes. Across all approvals, 72.9% drugs underwent evaluation through priority review, 41.1% were reviewed under fast-track status and 33.3% drugs were approved through accelerated pathway. Breakthrough therapy designation was given to 41.1% of drugs decreasing from 43.2% in 2020 to only 13.6% in 2023. PROs were evaluated in 61.7% of the pivotal trials for rare diseases; of which 89.4% of the trials assessed PROs as secondary or exploratory endpoints, and only 10.6% used PROs as primary endpoints.

CONCLUSIONS: This study demonstrates growing advancements and innovations in novel therapies for rare diseases, reflected by the increasing number of first-in-class therapies since 2020. Insights generated from this study also revealed the crucial role of PROs in assessing treatment efficacy and patients’ well-being.