6 BioPharm International eBook March 2021 www.biopharminternational.com
Growing Pipeline of Antisense
Oligonucleotides Prompts Guidance
FDA's newly proposed draft guidance will support IND
filings of antisense oligonucleotides, a new class of drugs.
F
ollowing decades of research and study, a
new class of drug, known as antisense oli-
gonucleotides (ASO), are maturing as drug
development efforts advance. In tandem with
a growing ASO pipeline, FDA has recently
issued a draft guidance for dealing with ASO investiga-
tional new drug (IND) filings (1).
WHY ASO GUIDANCE IS NEEDED
The importance of having regulatory guidance specifi-
cally for ASO lies in how these types of drugs are struc-
tured, says Michael V. Templin, PhD DABT, director,
Scientific Advisory Services at Charles River. "ASOs have
specific considerations for drug development, and regula-
tory documents are an effective means of formalizing sug-
gested steps and providing overall guidance. However, one
should consider not only the importance of guidance for
a new drug class but why oligonucleotide-based therapies,
including ASOs, deserve to be given class designation."
The structure of an ASO is based on the natural struc-
ture of DNA/RNA, Templin explains, and ASOs are depen-
dent on Watson-Crick base pairing between the ASO and
its target—most often messenger RNA, but non-coding
RNAs can also be targeted, and, "Hence, an ASO has both
a strict chemical structure and a precise mechanism for
activity, making ASOs distinct from small molecules and
biologics," Templin says.
Ultimately, an ASO can be applied to treat diseases/con-
ditions for which other drug classes may provide little or
no benefit. "Case in point," Templin continues, "advances
in molecular biology have allowed for the determination
of the exact sequence of a specific gene, and the ability to
identify mutations and/or insertions/deletions that lead to
disease. While an essential step forward, there has been
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