Savient Pharmaceuticals, Inc's Krystexxa

The FDA approved Krystexxa (pegloticase) Injection for the treatment of chronic gout in adult patients who are refractory to conventional therapy.

Savient Pharmaceuticals, inc’s Krystexxa

The FDA has granted approval for Krystexxa (pegloticase) Injection, a PEGylated uric acid—specific enzyme for the treatment of chronic gout in adult patients who are refractory to conventional therapy. 1 Refractory chronic gout occurs in patients whose serum uric acid has failed to normalize and whose signs and symptoms of gout remain uncontrolled despite maximum appropriate doses of xanthine oxidase inhibitors or in patients in whom those medications are contraindicated. 2 Krystexxa is manufactured by Savient Pharmaceuticals, Inc.

Pharmacology and Pharmacokinetics

Krystexxa is a recombinant uricase. It exhibits its effect by catalyzing the oxidation of uric acid to allantoin, which results in a lower serum uric acid. Allantoin is a purine metabolite that is both inert and water soluble and eliminated primarily by renal excretion. The pharmacokinetics of Krystexxa are not affected by age, sex, weight, or creatinine clearance. ¹

Dosing and Administration

For adult patients, the recommended dose of Krystexxa is 8 mg as an intravenous (IV) infusion every 2 weeks. Krystexxa should only be administered as an IV infusion over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump. Krystexxa should not be given as an IV push or bolus. Serum uric acid levels should be monitored before administering Krystexxa; if levels are above 6 mg/dL, consideration should be given to discontinuation of therapy, especially when 2 consecutive levels are above 6 mg/ dL. To minimize the risk of anaphylaxis and infusion reactions, patients should receive premedication with antihistamines and corticosteroids. Krystexxa should only be given in a health care setting by health care providers. ¹

Clinical Trials

Krystexxa was evaluated in 2 replicate, multicenter, randomized, double-blind, placebo-controlled clinical trials. Each study lasted 6 months. Patients were randomized to receive Krystexxa every 2 or 4 weeks or placebo in a ratio of 2:2:1. For both trials, the primary end point was the proportion of patients in whom plasma uric acid was reduced to less than 6 mg/dL for at least 80% of the time during months 3 and 6. In both trials, more patients receiving Krystexxa every 2 weeks reached this end point than patients receiving placebo: 47% (P <.001) and 38% (P <.001), compared with 0% in the placebo arms. ² Patients receiving Krystexxa every 4 weeks also achieved the primary end point; however, this regimen was associated with an increased frequency of infusion reactions and a decreased efficacy with the secondary end point. ¹

The secondary end point was the effect of Krystexxa on tophi, which are deposits of monosodium urate crystals in patients who have sustained long-term high levels of serum uric acid. Seventy-one percent of patients had baseline tophi. At 6 months, the combined data from both trials showed that 45% (P <.02) of patients receiving Krystexxa every 2 weeks had a complete response, which was considered 100% resolution of at least 1 target tophus, no new tophus developing, and no single tophus showing progression. In comparison, 8% of patients in the combined placebo arms achieved a complete response. ²

Precautions and Contraindications

Krystexxa carries a boxed warning regarding the potential for anaphylaxis and infusion reactions, both of which have been reported during and after treatment. The boxed warning describes the administration protocol to help minimize these reactions: administer in a health care setting by health care providers who are able to manage anaphylaxis, premedicate with antihistamines and corticosteroids, slow or stop the infusion if a reaction occurs, monitor closely after administration of Krystexxa, obtain serum uric acid levels prior to administration, and consider discontinuation of treatment if levels are above 6 mg/ dL, especially 2 consecutive levels above6 mg/dL, as the risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response.

Krystexxa is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as the risk of hemolysis and methemoglobinemia may be higher. Patients at higher risk of G6PD (for example, patients of African and Mediterranean ancestry) should be screened for G6PD prior to initiation of treatment with Krystexxa.

Initiation of treatment of an antihyperuricemic therapy, such as Krystexxa, often results in an increase in gout flares. Treatment with Krystexxa does not need to be discontinued if a gout flare occurs. Unless medically contraindicated or not tolerated, gout flare prophylaxis (nonsteroidal anti-inflammatory drug or colchicine) is recommended for at least the first 6 months of treatment with Krystexxa.

Krystexxa is pregnancy category C. It should not be administered to women who are breast-feeding. It is not approved for patients younger than 18 years. No dose adjustment is required for renal impairment. PT

Dr. Holmberg is a pharmacist who resides in Phonenix, Arizona.

References

1. Krystexxa complete prescribing information. www.krystexxa.com/pdfs/KRYSTEXXA_Prescribing_Information.pdf. Accessed March 2011.

2. FDA approves Krystexxa (pegloticase) for the treatment of chronic gout in adult patients refractory to conventional therapy. http://investor.savient.com/releasedetail.cfm?ReleaseID=507578. Accessed March 2011.