Phase II clinical study of Puricase for severe gout

Savient Pharmaceuticals has initiated a Phase II clinical study of Puricase, a polyethylene glycol (PEG) conjugate of uricase (urate oxidase), in the treatment of severe, refractory gout.

The Phase II multi-centre study will assess the effect of repeated intravenous administration of a range of doses and regimens of Puricase on uric acid levels, and its safety and tolerability, in patients with hyperuricemia and symptomatic severe refractory gout. Subjects selected for the study are not adequately treated by the conventional therapy, allopurinol, or are intolerant of it. No other approved therapy is currently available that adequately treats these refractory symptomatic patients.

In a Phase I single intravenous dose study completed in 2003 in patients with refractory gout, Puricase was well tolerated by all patients and appeared to be safe. Elevated plasma uric acid levels were reduced to well within the normal range and considerably below levels achieved with currently available therapies.

Sim Fass, chairman and ceo of Savient Pharmaceuticals stated: 'Our Phase I study has demonstrated that intravenous delivery of Puricase appears to be safe and well tolerated by patients with severe refractory gout. Additionally, it has provided us with very encouraging data that confirm its ability to reduce elevated plasma uric acid levels to normal. We expect our Phase II study, investigating the effect of multiple intravenous doses of Puricase, to be completed later this year. If it confirms the safety and tolerability of Puricase, together with sustained reduction of elevated uric acid levels in this refractory population, we will follow with a Phase III study. It is our belief that Puricase could become an important niche product, by providing relief to those gout sufferers who cannot benefit from currently available therapies.'

Gout problems

Uric acid is a very poorly soluble metabolite that is excreted by the kidneys. However, if excess uric acid accumulates, it can form needle shaped crystals in the joints and tissues causing painful tophi, gouty arthritis, and/or gouty kidney disease. Uricase is an enzyme produced by most mammals, though not by humans, that converts uric acid into allantoin, a highly soluble and easily excreted product. Puricase is a chemically modified form of recombinant uricase, based on mammalian sequences, under development by Savient for individuals with severe gout who cannot be treated adequately by conventional therapies.

Savient and gout

Savient has received FDA Orphan Drug designation for Puricase in the treatment of gout patients for whom conventional therapy is contraindicated or has been ineffective. It is estimated that there are approximately 32,000 individuals in the US who suffer from severe, untreatable gout.