Positive topline data were announced from a phase 4 trial evaluating the efficacy and safety pegloticase injection in combination with methotrexate to increase response rates in patients with chronic gout refractory to conventional therapies.
The double-blind, placebo-controlled MIRROR trial (ClinicalTrials.gov Identifier: NCT03994731) included 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.
The primary endpoint was the proportion of serum uric acid (sUA) responders, defined as sUA less than 6mg/dL at least 80% of the time during month 6.
Findings showed that 71% of patients treated with pegloticase plus methotrexate met the primary endpoint compared with 40% of those treated with pegloticase plus placebo (P <.001). There were no new safety concerns identified.
“It is rare that you can improve a response rate so substantially for patients; by 30 percentage points in this case based on the results of our trial,” said Elizabeth H.Z. Thompson, PhD, executive vice president, research and development, Horizon. “These results reinforce what we have seen from published case series as well as our open-label trial evaluating [pegloticase] with methotrexate.”
Results from the open-label MIRROR trial (ClinicalTrials.gov Identifier: NCT03635957) showed a response rate (sUA less than 6mg/dL) of 79% (n=11/14 patients) at month 6 when pegloticase was used with methotrexate.
Pegloticase is marketed under the brand name Krystexxa® and is currently approved as monotherapy for the treatment of chronic gout in adults refractory to conventional therapy.
As with other biologic therapies, anti-drug 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 anti-drug antibodies.
The Company plans to submit a supplemental Biologics License Application for co-therapy to the Food and Drug Administration (FDA) in the first quarter of 2022.
MIRROR randomized controlled trial meets primary endpoint and shows 71% of patients achieved a complete response rate using Krystexxa® (pegloticase injection) with methotrexate. News release. Horizon Therapeutics plc. October 25, 2021. Accessed October 26, 2021. https://ir.horizontherapeutics.com/news-releases/news-release-details/mirror-randomized-controlled-trial-meets-primary-endpoint-and.