Uricase-PEG 20
Polaris is working with EnzymeRx to clinically develop Uricase-PEG 20. A Phase I-II trial for treatment of chronic gout is tentatively scheduled to open in 2009.
Uricase-PEG 20 is a protein drug being developed as treatment for hyperuricemia, gout, and tumor lysis syndrome. Uricase (urate oxidase) is a naturally occurring enzyme produced in microbes and most mammals. This enzyme converts poorly soluble uric acid into highly soluble allantoin, preventing elevated uric acid levels from developing in the blood. However, humans are unable to express uricase due to presence of nonsense mutations in the gene coding for this enzyme. As a result, uric acid levels can become elevated in humans. When uric acid levels reach the point of saturation, crystals of uric acid precipitate out of solution in the blood and collect in various tissues and joints.
Uric acid is the final end product of purine metabolism, with purine being one of the two nitrogen-containing bases that make up DNA. Elevated levels of uric acid can arise from purine-rich diets, impaired kidney function or as a complication of having cancer chemotherapy (tumor lysis syndrome).
Uricase-PEG 20 is pegylated uricase from Candida utilis. The uricase is first produced in E. coli using recombinant technology and then formulated with polyethylene glycol (PEG) to decrease immunogenicity and extend circulating half-life in vivo. Treatment with Uricase-PEG 20 lowers the high uric acid levels associated with conditions such as gout and tumor lysis syndrome.