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 Pegloticase (KRYSTEXXA™) is a PEGylated uricase enzyme being developed as a treatment for chronic gout in patients refractory to conventional therapy. Pegloticase is administered as an intravenous infusion.
Chronic gout that is refractory to conventional therapy occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.
Gout develops when urate crystals, derivatives of uric acid, accumulate in the tissues and joints as a result of elevation of blood concentration of urate. The urate crystals induce an inflammatory response, with gouty arthritis the most common of inflammatory arthritis in adults. Gout is generally characterized by acute and often exquisitely painful and swollen joints and associated acute disability, known as gout flares. With chronic elevation of blood uric acid or urate, deposits of urate crystals can accumulate in tissues or in concentrated forms known as tophi. In addition, chronic elevations of uric acid are associated with both progression of the bony erosions and chronic disability associated with gouty arthritis and an associated increased risk of kidney failure and increased risk of cardiovascular disease.
Uricase is an enzyme that is not expressed in humans, but is present in almost all other mammals. Uricase eliminates uric acid from the body by converting it to allantoin, which is easily excreted by the kidney. Uric acid is poorly soluble in blood and tends to precipitate when the blood concentration reaches a level of approximately 6.8 mg/dL. Allantoin is more water soluble than urate and is eliminated from the body by the kidneys.
The PEGylated uricase, pegloticase, received orphan drug designation from the FDA in 2001. Pegloticase has demonstrated in two replicate, double-blind placebo-controlled clinical trials in those patients who have failed conventional xanthine oxidase therapy that those who respond to pegloticase maintain control of uric acid well below the level of 6 mg/dL.
Savient has completed the clinical development for pegloticase. The Phase 3 development was comprised of two replicate, multicenter, randomized, double-blind, placebo-controlled clinical trials comparing pegloticase 8 mg infused intravenously every two weeks or every four weeks to placebo in patients with chronic gout refractory to conventional therapy.
Patients completing these pivotal trials were eligible to enter an open label extension (OLE) study. In early July 2009, we completed the patient dosing phase of the OLE study, and in January 2010, we completed a protocol-specified six-month observation period for patients enrolled in this study.
For more information on the Phase 3 clinical trials, please refer to the following link: http://www.clinicaltrials.gov.
Savient has licensed worldwide rights to the technology related to pegloticase from Duke University and Mountain View Pharmaceuticals, Inc. KRYSTEXXA is a trademark of Savient Pharmaceuticals, Inc.
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