To support individualized ASO treatments for a small number of patients, the FDA recomends a limited nonclinical safety package than those intended to support broader use, or for use in less severe clinical circumstances.
PROOF OF CONCEPT
Sponsors should provide convincing in vitro and/or in vivo proof of concept (POC) data as part of any original investigational new drug (IND) submission for investigational antisense oligonucleotides.
SAFETY STUDIES
Sponsors should include the following nonclinical safety studies in their IND submission:
- Hybridization-dependent off-target assessment: Basic Local Alignment Search Tool (BLAST).
- Safety pharmacology:
- core safety pharmacology battery for systemically administered ASOs—cardiovascular, central nervous, and respiratory systems; can be combined into general toxicity study.
- central nervous system endpoints for products delivered directly to the central nervous system (e.g., intrathecally).