Pegaptanib is a synthetic, chemically modified RNA aptamer designed to selectively bind vascular endothelial growth factor 165 (VEGF165). It belongs to the oligonucleotide/aptamer class of pharmaceutical active ingredients and was developed as an anti-angiogenic treatment for neovascular (wet) age-related macular degeneration (AMD). Pegaptanib was approved by the FDA in 2004 and is administered by intravitreal injection as its sodium salt form.
The pharmaceutical active form is pegaptanib sodium, which is a covalent conjugate consisting of a chemically modified 28-nucleotide oligonucleotide aptamer linked to two branched polyethylene glycol (PEG) chains of approximately 20 kDa each. The overall PEG component is therefore approximately 40 kDa, and the complete conjugate has an approximate molecular weight of 50 kDa.
Pegaptanib sodium is associated with CAS Number 222716-86-1 and FDA UNII 3HP012Q0FH. The active moiety pegaptanib has FDA UNII 2H1PA8H1EN. FDA's current substance record classifies pegaptanib as an oligonucleotide and provides its detailed modified nucleotide sequence.
Unlike conventional small-molecule APIs, Pegaptanib does not have a simple fixed molecular weight in the same sense as a typical pharmaceutical compound. Its structure contains a defined oligonucleotide sequence together with PEG chains whose polymeric portion has a distribution of chain lengths.
The FDA description gives the pegaptanib sodium molecular formula in polymeric form as:
C294H342F13N107Na28O188P28[C2H4O]n
where n is approximately 900 for the combined PEG component. The resulting molecular weight is approximately 50 kilodaltons.
The FDA GSRS record identifies pegaptanib sodium as an oligonucleotide and provides the 28-base sequence:
CGGAAUCAGUGAAUGCUUAUACAUCCGT
The sequence contains chemically modified nucleotides, including 2′-fluoro, 2′-O-methyl, unmodified ribonucleotide residues and a terminal modified thymidine.
Pegaptanib is specifically designed as a PEGylated aptamer. Two branched 20-kDa monomethoxy polyethylene glycol units are attached through a lysine-containing linker. PEGylation increases the molecular size and helps extend the residence time of the molecule following administration.
The PEG chains are an important part of the pharmaceutical substance and should not be treated simply as an excipient. The complete pegaptanib sodium drug substance is a defined oligonucleotide-PEG conjugate.
Pegaptanib selectively binds the VEGF165 isoform of vascular endothelial growth factor. VEGF165 contributes to pathological ocular angiogenesis and increased vascular permeability associated with neovascular AMD.
By binding VEGF165, pegaptanib prevents VEGF165 from interacting effectively with its receptors. This reduces VEGF-mediated angiogenesis and vascular permeability in the eye. Pegaptanib is designed to selectively target VEGF165 rather than broadly inhibiting all VEGF isoforms.
This mechanism makes pegaptanib distinct from conventional small-molecule anti-inflammatory drugs and from antibodies such as anti-VEGF monoclonal antibodies.
Pegaptanib sodium is associated primarily with the treatment of neovascular or wet age-related macular degeneration. The pharmaceutical product Macugen contains pegaptanib sodium and is formulated as a sterile aqueous solution for intravitreal administration.
The historical development of pegaptanib represents an important milestone in therapeutic oligonucleotide technology because it was the first FDA-approved aptamer drug.
Potential pharmaceutical and research applications include:
The FDA label describes Macugen as a sterile, clear, preservative-free aqueous solution for intravitreal injection. The product contains pegaptanib sodium together with sodium chloride, phosphate buffers, water for injection and pH-adjusting agents.
The labeled product contains 0.3 mg of the free-acid oligonucleotide form in a nominal 90 µL dose. This corresponds to approximately 1.6 mg of pegaptanib sodium when expressed as the PEGylated sodium form.
The finished product specification includes pharmaceutical tests such as pH, osmolality, sterility, endotoxin and particulate contamination. These are finished-product requirements and should not automatically be presented as universal bulk API specifications.
Pegaptanib requires analytical approaches appropriate for complex oligonucleotide therapeutics rather than conventional small-molecule API testing alone.
Important quality attributes can include:
The PMDA review describes pegaptanib sodium as a 28-mer synthetic oligonucleotide aptamer covalently linked to PEG chains and notes characterization of physical description, solubility, hygroscopicity, thermal properties, pH, optical activity and biological activity.
Because Pegaptanib is an oligonucleotide-PEG conjugate, suitable analytical characterization can involve:
A conventional “Assay (HPLC) 98–102%” should not be invented for this product. Pegaptanib is a complex polymeric oligonucleotide conjugate, and its quality specification depends on the approved drug-substance specification and validated analytical methods.
Pegaptanib sodium is a hygroscopic drug substance and requires controlled handling to protect its chemical and structural integrity. PMDA documentation describes the drug substance as a white to slightly colored powder and reports that it is deliquescent.
For research material, commercial documentation commonly recommends frozen, sealed and moisture-protected storage. However, the final storage condition for pharmaceutical API manufacturing should follow the applicable validated stability program and approved specification.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | ≤ 1.5% |