Amgen Presents Positive Data for UPLIZNA in IgG4-Related Disease and KRYSTEXXA in Uncontrolled Gout at ACR 2024
核心洞察
UPLIZNA demonstrated an 87% reduction in IgG4-RD flare risk compared to placebo in the Phase 3 MITIGATE study, with significant improvements in remission rates.
The MITIGATE study also showed that 89.7% of UPLIZNA-treated patients required no glucocorticoid treatment for disease control during the placebo-controlled period.
AGILE trial data support shortening KRYSTEXXA infusion time to 60 minutes when co-administered with methotrexate for uncontrolled gout (搜索), maintaining similar efficacy and safety.
Amgen presented new data from studies evaluating UPLIZNA® (inebilizumab-cdon) in Immunoglobulin G4-Related Disease (IgG4-RD) and KRYSTEXXA® (pegloticase) in uncontrolled gout (搜索) at the American College of Rheumatology (ACR) Convergence 2024 conference. The findings reinforce Amgen's commitment to developing innovative treatments for rare inflammatory diseases.
UPLIZNA Shows Significant Efficacy in IgG4-RD
The Phase 3 MITIGATE study, the first randomized, double-blind, placebo-controlled trial in IgG4-RD, assessed the efficacy and safety of UPLIZNA, a CD19 (搜索)+ B-cell depleting antibody. Results, simultaneously published in the New England Journal of Medicine, demonstrated a clinically meaningful and statistically significant 87% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.13, p<0.001) during the 52-week placebo-controlled period. Specifically, 7 out of 68 participants receiving UPLIZNA experienced a flare compared to 40 out of 67 participants receiving placebo.
The study also revealed a reduction in the annualized flare rate for treated and adjudication committee-determined flares during the placebo-controlled period: 0.10 for participants receiving UPLIZNA compared to 0.71 for participants receiving placebo (p<0.001). Furthermore, 57.4% of participants receiving UPLIZNA achieved flare-free, treatment-free, complete remission at Week 52 compared to 22.4% of participants receiving placebo (p<0.001), and 58.8% of participants receiving UPLIZNA achieved flare-free, corticosteroid-free, complete remission at Week 52 compared to 22.4% of participants receiving placebo (p<0.001).
Notably, 89.7% of UPLIZNA-treated patients required no glucocorticoid treatment for disease control during the placebo-controlled period, compared to 37.3% of patients on placebo. After Week 8, UPLIZNA-treated patients experienced a ten-fold reduction in total glucocorticoid use relative to placebo.
The safety profile of UPLIZNA in the placebo-controlled period was consistent with its established safety profile. The most common treatment-emergent adverse events included COVID-19, lymphopenia, urinary tract infection, and headache.
KRYSTEXXA Infusion Time Reduced with Methotrexate Co-administration
The AGILE trial evaluated the safety, tolerability, and efficacy of KRYSTEXXA administered with a shorter infusion duration in patients with uncontrolled gout (搜索) receiving methotrexate as co-administration. Data from the 60-minute infusion duration cohort showed similar safety and efficacy to the MIRROR randomized clinical trial and current administration of KRYSTEXXA with methotrexate over at least 120 minutes.
Key findings include that 67.2% of participants receiving a 60-minute infusion duration of KRYSTEXXA with methotrexate achieved and maintained a response during Month 6, defined as a urate level of < 6mg/dL for ≥80% of the time. Additionally, 6.0% of participants receiving a 60-minute infusion duration of KRYSTEXXA with methotrexate experienced an infusion reaction, including anaphylaxis (1.7%).
These data support the potential for a shorter infusion time for KRYSTEXXA when co-administered with methotrexate, potentially improving the patient experience.
Implications for Rare Disease Treatment
"These data add to the growing body of evidence for UPLIZNA and KRYSTEXXA and strengthen our commitment to developing new treatment options for rare diseases like IgG4-RD and uncontrolled gout (搜索)," said Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen. "Patients living with these debilitating conditions deserve new approaches targeting the underlying causes of disease, potentially improving outcomes and enhancing the overall treatment experience."