General Information

Krystexxa is a uric acid specific enzyme, a recombinant uricase, 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.

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.

Side Effects

Adverse events associated with the use of Krystexxa may include, but are not limited to, the following:

Gout flares

Infusion reactions

Nausea

Contusion or ecchymosis

Nasopharyngitis

Constipation

Chest pain

Anaphylaxis

Vomiting

Dosing/Administration

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 Trial Results

FDA approval of Kyrstexxa was based on two replicate, multicenter, randomized, double-blind, placebo-controlled studies of six months duration: trial one and trial two. The trials enrolled adult patients with chronic gout refractory to conventional therapy, who were randomized to receive Krystexxa 8 mg every two weeks or every four weeks or placebo. The studies were stratified for the presence of tophi: 71 percent 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 percebt of the time during month three and month six. Data showed that a greater proportion of patients treated with Krystexxa every two weeks achieved urate lowering to below 6 mg/dL than patients receiving placebo. Although the four 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 two weeks: 47 percent responders; Pegloticase 8 mg every four weeks: 20 percent responders and placebo: zero percent responders.

Trial Two
Pegloticase 8 mg every twp weeks: 38 percent responders; Pegloticase 8 mg every four weeks: 49 percent responders and placebo zero percent responders.

The effect of treatment on tophi was a secondary efficacy endpoint. A pooled analysis was conducted. At month six, the percentage of patients who achieved a complete response (defined as 100 percent resolution of at least one target tophus, no new tophi and no single tophus showing progression) was 45 percent, 26 percent and 8 percent, with Krystexxa 8 mg every two weeks, Krystexxa 8 mg every four weeks and placebo, respectively. The difference between Krystexxa and placebo was statistically significant for the every-two-week dosing regimen, but not for the every-four-week dosing regimen.