SOMAVERT contains pegvisomant, an analog of human growth hormone (GH) that has been structurally altered to act as a GH receptor antagonist.
Pegvisomant is a protein of recombinant DNA origin containing 191 amino acid residues to which several polyethylene glycol (PEG) polymers are covalently bound (predominantly 4 to 6 PEG/protein molecule). The molecular weight of the protein of pegvisomant is 21,998 Daltons. The molecular weight of the PEG portion of pegvisomant is approximately 5000 Daltons. The predominant molecular weights of pegvisomant are thus approximately 42,000, 47,000, and 52,000 Daltons. The schematic shows the amino acid sequence of the pegvisomant protein (PEG polymers are shown attached to the 5 most probable attachment sites). Pegvisomant is synthesized by a specific strain of Escherichia coli bacteria that has been genetically modified by the addition of a plasmid that carries a gene for GH receptor antagonist. Biological potency is determined using a cell proliferation bioassay. Binding of Somavert to the GH receptor results in disruption of the proper binding of the second GH receptor with inhibition of functional receptor dimerization and subsequent intracellular signaling.
Stippled residues indicate PEG attachment sites (Phe1, Lys38, Lys41, Lys70, Lys115, Lys120, Lys140, Lys145, Lys158)
Shown below are the amino acid substitutions in pegvisomant, relative to human GH.
SOMAVERT for injection is supplied as a sterile, white lyophilized powder intended for subcutaneous injection after reconstitution with 1 mL of Sterile Water for Injection. SOMAVERT is available in single-dose sterile vials containing 10, 15, 20, 25 or 30 mg of pegvisomant protein (approximately 10, 15, 20, 25 and 30 U activity, respectively). Each vial 10, 15 and 20 also contains 1.36 mg of glycine, 36.0 mg of mannitol, 1.04 mg of sodium phosphate dibasic anhydrous, and 0.36 mg of sodium dihydrogen phosphate monohydrate. Each 25 mg vial also contains 1.7 mg of glycine, 45 mg of mannitol, 1.3 mg of sodium phosphate dibasic anhydrous, and 0.45 mg of sodium dihydrogen phosphate monohydrate. Each 30 mg vial also contains 2.04 mg of glycine, 54 mg of mannitol, 1.56 mg of sodium phosphate dibasic anhydrous, and 0.54 mg of sodium dihydrogen phosphate monohydrate.
SOMAVERT is supplied in packages that include a vial containing diluent. Sterile Water for Injection, USP, is a sterile, nonpyrogenic preparation of water for injection that contains no bacteriostat, antimicrobial agent, or added buffer, and is supplied in single-dose containers to be used as a diluent.