Fomivirsen sodium

A. General description Fomivirsen sodium (molecular weight about 7kDa) is a phosphorothioate oligonucleotide, 21 nucleotides in length, with the following sequence 5 -GCG TTT GCT CTT CTT CTT GCG-3. ... 

Dosage form Vitravene is a sterile, aqueous, preservative-free, buffered solution supplied in 0.25 ml single-use vials for intravitreal injection. Each ml of Vitravene solution contains fomivirsen sodium 6.6 mg. 

Disposition Metabolites of fomivirsen are detected in the retina and vitreous humor in animals. Fomivirsen sodium is metabolized by exonucleases in a process that sequentially removes residues from the terminal ends of the oligonucleotide yielding shortened oligonucleotides and mononucleotide metabolites. 

Fomivirsens sodium, antisense nucleotide polymer against CMV... 

ASOs are synthesized as complex mixtures of diastereomers. In the solid state, they are amorphous, electrostatic, hygroscopic solids with low-bulk densities, possessing very high surface areas, and poorly defined or no melting points. Their good chemical stability allows them to be stored as lyophilized or spray-dried powders, or as concentrated, sterile solutions. For example, the 21-mer ASO Vitrave-ne (fomivirsen sodium intravitreal injectable) is approved in the USA for a storage condition from 2 to 25 °C [2]. 

Vitravene (fomivirsen sodium, ISIS Pharmaceuticals see Table 9) remains the only antisense-based biopharmaceutical approved for general medical use (see also Part III, Chapter 3). The product is a 21-base phosphorothioate nucleotide that displays a base sequence complementary to certain human cytomegaloviral mRNA transcripts. Its administration inhibits viral replication through an antisense mechanism. Approved in the US in 1998 and in the EU in 1999, the product is indicated for the treatment of cytomegalovirus retinitis by intraocular injection in AIDS patients. It was withdrawn from the EU market in May 2002 for commercial reasons. 

Piascik P. Fomivirsen sodium approved to treat CMV retinitis. J Am Pharm Assoc 1 999 39 84-85. 

---