Horizon Therapeutics plc announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) expanding the labeling to include KRYSTEXXA (pegloticase) injection co-administered with methotrexate, which will help more people with uncontrolled gout achieve a complete response to therapy.
“Today’s approval for KRYSTEXXA with methotrexate is the culmination of more than five years of effort and demonstrates Horizon’s commitment to working together with the gout community to improve the patient experience and outcomes,” said Elizabeth H.Z. Thompson, Ph.D., executive vice president, research and development, Horizon. “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 expanded labeling for KRYSTEXXA with methotrexate is based on the results from the MIRROR randomized controlled trial in which adults living with uncontrolled gout were randomized to receive methotrexate (15 mg/week) or placebo for four weeks, and then treatment with KRYSTEXXA with methotrexate or KRYSTEXXA with placebo for 52 weeks. The primary endpoint was defined as the proportion of serum uric acid (sUA) responders during Month 6 (defined as sUA less than 6 mg/dL at least 80% of the time).
“Uncontrolled gout carries serious, long-term consequences in the joints and throughout the body, as well as a significant impact on a person’s daily life,” said co-primary investigator John K. Botson, M.D., R.Ph., C.C.D., president, Alaska Rheumatology Alliance and rheumatologist, Orthopedic Physicians Alaska. “Through multiple in-practice case series, the open-label trial and the randomized controlled trial, the medical community has been actively engaged in finding ways to reduce the impact of uncontrolled gout by maximizing the use of KRYSTEXXA. The expanded labeling reflects robust data on this treatment approach, which can allow us to change outcomes for many uncontrolled gout patients, most of whom have no other treatment option.”
The MIRROR randomized controlled trial results reinforced a substantial body of data supporting the use of KRYSTEXXA with methotrexate. Results included:
- Greater than 30 percentage-point increase in patient response rate during Month 6 (p<0.0001): 71% (71 of 100) of patients randomized to receive KRYSTEXXA with methotrexate vs 39% (20 of 52) of patients randomized to receive KRYSTEXXA with placebo achieved the primary endpoint (defined as sUA less than 6 mg/dL at least 80% of the time during Month 6).
- Improvement in the patient response rate remained nearly 30 percentage points higher during Month 12 (p<0.001): 60% (60 of 100) of patients randomized to receive KRYSTEXXA with methotrexate achieved a complete response during Month 12 compared to 31% (16 of 52) of patients randomized to receive KRYSTEXXA with placebo. Complete response is defined as sUA less than 6 mg/dL at least 80% of the time during Month 12.
- Marked reduction in infusion reactions: during the treatment period, 4% (4 of 96) of patients who received KRYSTEXXA with methotrexate experienced infusion reactions vs 31% (15 of 49) of patients who received KRYSTEXXA with placebo. No new safety signals were observed.
- Over a 22 percentage-point increase in the complete resolution of at least one tophus at Month 12 (p=0.048): among patients with validated tophi at baseline, 54% (28 of 52) of patients randomized to receive KRYSTEXXA with methotrexate had complete resolution of at least one tophus, no new tophus and no single tophus showing progression at Week 52 vs 31% (9 of 29) of patients randomized to receive KRYSTEXXA with placebo.