Hyperuricemia results from an imbalance between the rates of production and excretion of
uric acid. Longstanding
hyperuricemia can lead to
gout, which is characterized by the deposition of
monosodium urate monohydrate crystals in the joints and periarticular structures. Because such deposits are resolved very slowly by lowering plasma
urate with available drugs or other measures, the symptoms of
gout may become chronic. Persistent
hyperuricemia may also increase the risk of renal and
cardiovascular diseases. Unlike most mammals, humans lack the
enzyme uricase (
urate oxidase) that catalyzes the oxidation of
uric acid to a more soluble product. This review describes the development of a poly(
ethylene glycol) (PEG) conjugate of recombinant porcine-like
uricase with which a substantial and persistent reduction of plasma
urate concentrations has been demonstrated in a Phase 2 clinical trial. Two ongoing Phase 3 clinical trials include systematic assessments of
gout symptoms, tophus resolution and quality of life, in addition to the primary endpoint of reduced plasma
urate concentration.