FDA Approves Pegloticase Injection Plus Methotrexate for Patients with Uncontrolled Gout

The US Food and Drug Administration (FDA) expanded the pegloticase label to include the co-treatment of pegloticase (KRYSTEXXA) injection plus methotrexate in patients with uncontrolled gout. The decision was based on results from the MIRROR trial, which evaluated the concomitant use of pegloticase with methotrexate, a commonly prescribed immunomodulator, to help more patients attain a complete and long-lasting response to therapy.

“Today’s approval for KRYSTEXXA with methotrexate is the culmination of more than 5 years of effort and demonstrates Horizon’s commitment to working together with the gout community to improve the patient experience and outcomes,” Elizabeth HZ Thompson, PhD, executive vice president, research and development, Horizon, stated. “Immunomodulatory therapies like methotrexate are often used with biologics to reduce the development of anti-drug antibodies and allow more patients to achieve a complete response. We anticipate this approval will encourage more physicians to recommend KRYSTEXXA with methotrexate to help their patients with uncontrolled gout receive the full benefits of KRYSTEXXA.”

The Trial

The phase 4, randomized, placebo-controlled MIRROR trial included 152 adult patients with uncontrolled gout who were randomized to receive either methotrexate or placebo for 4 weeks and then pegloticase and methotrexate or pegloticase and placebo combination therapy for 52 weeks. The primary endpoint was defined as the proportion of serum uric acid (sUA) responders (as defined by sUA <6 mg/dL 80% or more of the time during month 6).

Pegloticase was shown to be effective in 71% (71 of 100) of patients in the methotrexate cohort, compared with 39% (20 of 52) in the placebo group. The randomized controlled trial followed the open-label trial (NCT03635957), which showed that the majority of patients (79%, 11/14 patients) had a sUA <6 mg/dL response rate at month 6 when patients received pegloticase plus methotrexate. While the studies were limited by the small sample sizes, no new safety concerns were reported.

The Drug

Pegloticase, a recombinant uricase enzyme that converts urate into allantoin that is more easily excreted from the body, is a PEGylated uric acid specific enzyme injection indicated for treating chronic gout in adult patients refractory to conventional therapy. The most commonly reported adverse events were gout flares, nausea, vomiting, infusion reactions, constipation, chest pain, nasopharyngitis, anaphylaxis, and contusion or ecchymosis.