Regulatory considerations for evaluating the pharmacology and toxicology of antisense drugs.
This article focuses on pharmacology and toxicology data that should be included in an Investigational New Drug Application (IND), a request to use an investigational drug in clinical trials. In general, pharmacology and toxicology testing programs for antisense compounds are held to the same regulatory standards applied to other new therapeutic classes. Biological properties of oligonucleotide therapeutics are mentioned where they may pertain to clinical safety issues. Nonclinical data submitted to the IND should characterize the pharmacology, disposition, and toxicology of a new drug; these data form the basis for clinical risk assessment. Concomitant evaluation of pharmacokinetics allows for better interpretation of in vivo studies and increased accuracy of dose extrapolation to humans. Recommendations for nonclinical drug development will be modified as new information regarding the biological properties of oligonucleotides becomes available.
Black
L E
LE
Food and Drug Administration, Committee on Antisense Pharmacology and Toxicology, Rockville, Maryland 20852.
Degeorge
J J
JJ
Cavagnaro
J A
JA
Jordan
A
A
Ahn
C H
CH
D000818:Animals; D016465:Bone Marrow Purging; D002986:Clinical Trials as Topic; D015507:Drugs, Investigational / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D017387:Investigational New Drug Application; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D014481:United States; D014486:United States Food and Drug Administration
D015507:Drugs, Investigational; D016376:Oligonucleotides, Antisense