A supplemental Biologics License Application (sBLA) has been submitted to the Food and Drug Administration (FDA) for pegloticase injection plus methotrexate for the treatment of uncontrolled gout. Pegloticase is currently marketed under the brand name Krystexxa® as monotherapy for chronic gout in adults refractory to conventional therapy.
The sBLA submission is supported by data from the double-blind, placebo-controlled phase 4 MIRROR trial (ClinicalTrials.gov Identifier: NCT03994731), which evaluated the efficacy and safety of pegloticase, a PEGylated uric acid specific enzyme, 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.
Results showed that 71% of patients treated with pegloticase plus methotrexate met the primary endpoint achieving a complete serum uric acid response (sUA), defined as sUA less than 6mg/dL at least 80% of the time during month 6, compared with 38.5% of those treated with pegloticase plus placebo (P <.0001). There were no new safety concerns identified.
“Since 2018, we have seen a paradigm shift in uncontrolled gout care, which has been reinforced by the positive MIRROR randomized controlled trial results,” said Theresa Podrebarac, MD, MSc, senior vice president, clinical development, Horizon. “Today’s filing reflects these trends and will help to further evolve the standard of care in uncontrolled gout.”
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 FDA expects to complete its review of the sBLA during the second half of 2022.
Horizon Therapeutics plc submits supplemental Biologics License for the concomitant use of Krystexxa® (pegloticase injection) plus methotrexate for people living with uncontrolled gout. News release. Horizon Therapeutics plc. Accessed January 10, 2022. https://www.businesswire.com/news/home/20220110005332/en/Horizon-Therapeutics-plc-Submits-Supplemental-Biologics-License-for-the-Concomitant-Use-of-KRYSTEXXA%C2%AE-pegloticase-injection-Plus-Methotrexate-for-People-Living-with-Uncontrolled-Gout.