Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics Guidance for Industry JUNE 2024

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-pharmacology-considerations-development-oligonucleotide-therapeutics?utm_medium=email&utm_source=govdelivery On June 17, 2024, the FDA announced the availability of a final guidance for industry entitled Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics, replacing the June 2022 draft guidance on this topic. Oligonucleotide therapeutics are an emerging therapeutic modality with increasing numbers of drugs in development. Oligonucleotide therapeutics include a wide variety of synthetically modified RNA or RNA/DNA hybrids that are specifically designed to bind to a target RNA sequence to alter RNA expression and/or downstream protein expression. Many antisense and small interfering RNA (siRNA) oligonucleotide therapeutics have been FDA-approved in recent years. In addition, increasing numbers of oligonucleotide therapeutics are currently in development. Oligonucleotide therapeutics have unique characteristics compared to small molecule drugs or biological products (e.g., chemistry, structure, sites of action, pharmacokinetic disposition, pharmacodynamics). Therefore, several factors should be considered in determining which studies are needed to characterize the clinical pharmacology of these products. This final guidance provides the FDA’s recommendations to assist industry in the development of oligonucleotide therapeutics. Specifically, it provides the FDA’s recommendations for certain evaluations during development of oligonucleotide therapeutics, including: (1) characterizing the potential for QTc interval prolongation, (2) performing immunogenicity risk assessment, (3) characterizing the impact of hepatic and renal impairment, and (4) assessing the potential for drug-drug interactions. This guidance also provides recommendations on when to conduct these assessments and what types of assessments are suitable to address the topics listed above.