The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for the use of pegloticase injection plus methotrexate for the treatment of uncontrolled gout.

Pegloticase, a PEGylated uric acid specific enzyme, is currently marketed under the brand name Krystexxa® as monotherapy for chronic gout in adults refractory to conventional therapy. As with other biologic therapies, antidrug antibodies can develop in patients preventing them from completing a full course of treatment. The addition of immunomodulating therapy such as methotrexate has been shown to reduce the development of antidrug antibodies.

The sBLA includes data from the double-blind, placebo-controlled phase 4 MIRROR trial ( Identifier: NCT03994731), which evaluated the efficacy and safety of pegloticase plus methotrexate in 152 adults with uncontrolled gout. Patients were randomly assigned to receive methotrexate or placebo for 4 weeks, then pegloticase in combination with either methotrexate (n=100) or placebo (n=52) for 52 weeks.

Findings from the trial showed that treatment with pegloticase plus methotrexate met the primary endpoint demonstrating a statistically significant improvement in complete serum uric acid response compared with pegloticase plus placebo. There were no new safety concerns identified. 

A Prescription Drug User Fee Act (PDUFA) target date of July 7, 2022 has been assigned to the application.


Horizon Therapeutics plc announces FDA has granted Priority Review of the supplemental Biologics License Application (sBLA) for the concomitant use of Krystexxa® (pegloticase injection) plus methotrexate for people living with uncontrolled gout. News release. Horizon Therapeutics plc. Accessed March 7, 2022.