Pegloticase

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Vidit Bhargava, M.B.B.S [2]

Synonyms / Brand Names: KRYSTEXXA

Overview

Pegloticase (trade name Krystexxa, formerly Puricase) is a drug for the treatment of severe, treatment-refractory, chronic gout, developed by Savient Pharmaceuticals. In September 2010, the FDA approved pegloticase for marketing in the United States after two clinical trials demonstrated the drug lowered uric acid levels and reduced deposits of uric acid crystals in joints and soft tissue. The European Medicines Agency (EMA) granted marketing authorization in January 2013 for treatment of disabling tophaceous gout. Pegloticase is the first and only drug approved for this indication.

The drug is administered intravenously.

Mechanism

Pegloticase is a recombinant porcine-like uricase. Similarly to rasburicase, it metabolises uric acid to allantoin. This reduces the risk of precipitates, since allantoin is five to ten times more soluble than uric acid.

In contrast to rasburicase, pegloticase is pegylated to increase its elimination half-life from about eight hours to ten or twelve days, and to decrease the immunogenicity of the foreign uricase protein. This modification allows for an application just once every two to four weeks, making this drug suitable for long-term treatment.

Side Effects

Pegloticase may show immunogenicity. Anaphylaxis and infusion reactions have been reported to occur during and after administration of the drug.

Chemistry

Pegloticase is a tetrameric peptide composed of four identical chains of about 300 amino acids each. Approximately nine of the 30 lysine residues in each chain are pegylated. These side chains consist of about 225 ethylene glycol units each.