A Review on Commercial Oligonucleotide Drug Products

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Biotechnology

Background:

• Oligonucleotide therapeutics represent a rapidly growing class of drugs.
• Understanding formulation and delivery attributes is crucial for successful drug development.
• Commercialization requires robust formulation strategies for diverse administration routes.

Purpose of the Study:

• To review and analyze commercially approved oligonucleotide drug products in the US and EU.
• To identify common formulation characteristics, administration routes, and packaging for oligonucleotide drugs.
• To propose a generalized formulation starting point for early-phase oligonucleotide drug development.

Main Methods:

• Systematic review of 20 approved oligonucleotide drug products.
• Analysis of drug product composition, concentration, pH, administration routes, and primary packaging.
• Data compilation to identify common attributes and trends.

Main Results:

• Identified 20 products: 1 aptamer, 12 antisense oligonucleotides (ASOs), 6 small interfering ribonucleic acids (siRNAs), and 1 mixture.
• Typical formulations contain oligonucleotides with buffering, pH adjusting, and tonicity adjusting agents.
• Products are solutions (2.1-200 mg/mL, pH 6-8.7), primarily for intravenous (IV) and subcutaneous (SC) routes, with vials and prefilled syringes (PFS) as primary packaging.

Conclusions:

• A generalized formulation starting point can be proposed for early-phase development of oligonucleotide drugs for IV, SC, and intrathecal (IT) routes.
• Harmonized evaluation of drug product attributes facilitates platform generalizations.
• This approach can accelerate early-phase development, including first-in-human studies.