Senior Pharmacologist US FDA Silver Spring, Maryland, United States
Oligonucleotide therapies represent a multivariant drug modality with IND submissions for a variety of indications across multiple divisions in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA). In the last decade, multiple antisense and siRNA oligonucleotide drugs have been approved primarily for rare disease indications with emerging applications for more common diseases. Inspired by the success of targeted delivery of oligonucleotides to hepatocytes via GalNAc-conjugation, antibody and peptide conjugates have been formulated for targeting and delivery to non-hepatic tissues for disease indications including genetic neuromuscular diseases and cancer. Consistent with the absence of an oligonucleotide-specific guidance, sources of regulatory recommendations for antibody/peptide oligonucleotide conjugates have included the ICH S6(R1), ICH M3(R2), and ICH S9 guidances. Examples of nonclinical studies submitted and/or requested by the FDA for successful programs for different categories of antibody/peptide conjugates and different disease indications will be contrasted with descriptions of submissions considered to be deficient.
