General Information

Krystexxa is a uric acid specific enzyme, which is a recombinant uricase, and achieves its therapeutic effect by catalyzing the oxidation of uric acid to allantoin, thereby lowering serum uric acid. Allantoin is an inert and water soluble purine metabolite. It is readily eliminated, primarily by renal excretion.

Krystexxa is specifically indicated for the treatment of chronic gout in adult patients refractory to conventional therapy.

Krystexxa is supplied as a solution intended for intravenous infusion after dilution. The recommended initial dose is 8mg (uricase protein) given as an intravenous infusion every two weeks.

Clinical Results

FDA Approval
The FDA approval of Kyrstexxa was based on two replicate, multicenter, randomized, double-blind, placebo-controlled studies of six months duration: Trial 1 and Trial 2. The trials enrolled adult patients with chronic gout refractory to conventional therapy who were randomized to receive Krystexxa 8 mg every 2 weeks or every 4 weeks or placebo. The studies were stratified for the presence of tophi: 71% of patients had baseline tophi. The primary endpoint in both trials was the proportion of patients who achieved plasma uric acid (PUA) less than 6 mg/dL for at least 80% of the time during Month 3 and Month 6. Data showed that a greater proportion of patients treated with Krystexxa every 2 weeks achieved urate lowering to below 6 mg/dL than patients receiving placebo. Although the 4 week regimen also demonstrated efficacy for the primary endpoint, this regimen was associated with increased frequency of anaphylaxis and infusion reactions and less efficacy with respect to tophi.
Trial One
Pegloticase 8 mg every 2 weeks: 47% responders; Pegloticase 8 mg every 4 weeks: 20% responders and placebo: 0% responders.
Trial Two
Pegloticase 8 mg every 2 weeks: 38% responders; Pegloticase 8 mg every 4 weeks: 49% responders and placebo 0% responders.
The effect of treatment on tophi was a secondary efficacy endpoint. A pooled analysis was conducted. At Month 6, the percentage of patients who achieved a complete response (defined as 100% resolution of at least one target tophus, no new tophi appear and no single tophus showing progression) was 45%, 26%, and 8%, with Krystexxa 8 mg every 2 weeks, Krystexxa 8 mg every 4 weeks, and placebo, respectively. The difference between Krystexxa and placebo was statistically significant for the every 2 week dosing regimen, but not for the every 4 week dosing regimen.

Mechanism of Action

Krystexxa is a uric acid specific enzyme which is a PEGylated product that consists of recombinant modified mammalian urate oxidase (uricase) produced by a genetically modified strain of Escherichia coli. It achieves its therapeutic effect by catalyzing the oxidation of uric acid to allantoin, thereby lowering serum uric acid. Allantoin is an inert and water soluble purine metabolite. It is readily eliminated, primarily by renal excretion.

Literature References

Baraf HS, Matsumoto AK, Maroli AN, Waltrip RW 2nd Resolution of gouty tophi after twelve weeks of pegloticase treatment. Arthritis and Rheumatism 2008 Nov;58(11):3632-4

Sundy JS, Becker MA, Baraf HS, Barkhuizen A, Moreland LW, Huang W, Waltrip RW 2nd, Maroli AN, Horowitz Z; Pegloticase Phase 2 Study Investigators Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: results of a phase II randomized study. Arthritis and Rheumatism 2008 Sep;58(9):2882-91