Getting the Dose Right in Drug Development for Rare Diseases: Barriers and Enablers.

Publisher: Wiley Country of Publication: United States NLM ID: 0372741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-6535 (Electronic) Linking ISSN: 00099236 NLM ISO Abbreviation: Clin Pharmacol Ther Subsets: MEDLINE

Publication: 2015- : Hoboken, NJ : Wiley
Original Publication: St. Louis : C.V. Mosby

Drug Development*/methods ; Rare Diseases*/drug therapy; Animals ; Humans ; Dose-Response Relationship, Drug

In the relentless pursuit of optimizing drug development, the intricate process of determining the ideal dosage unfolds. This involves "dose-finding" studies, crucial for providing insights into subsequent registration trials. However, the challenges intensify when tackling rare diseases. The complexity arises from poorly understood pathophysiologies, scarcity of appropriate animal models, and limited natural history understanding. The inherent heterogeneity, coupled with challenges in defining clinical end points, poses substantial challenges, hindering the utility of available data. The small affected population, low disease awareness, and restricted healthcare access compound the difficulty in conducting dose-finding studies. This white paper delves into critical dose selection aspects, focusing on key therapeutic areas, such as oncology, neurology, hepatology, metabolic rare diseases. It also explores dose selection challenges posed by pediatric rare diseases as well as novel modalities, including enzyme replacement therapies, cell and gene therapies, and oligonucleotides. Several examples emphasize the pivotal role of clinical pharmacology in navigating the complexities associated with these diseases and emerging treatment modalities.
(© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

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Date Created: 20240816 Date Completed: 20241115 Latest Revision: 20241118

20241119

10.1002/cpt.3407

39148459