Amgen announced the presentation of new data across its rare disease portfolio at the annual American College of Rheumatology (ACR) Convergence 2024 conference.

New data showcase reduction in disease activity by Uplizna (inebilizumab-cdon) in Immunoglobulin G4-Related Disease (IgG4-RD) and support shorter infusion times for Krystexxa (pegloticase) co-administered with weekly oral methotrexate 15 mg.

"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," 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."

Key presentations include: 1.A Phase III, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study of Inebilizumab in IgG4-Related Disease (MITIGATE): Primary Efficacy and Safety Findings. Abstract #0775, Abstract Session: Saturday, Nov. 16 from 1:00 p.m. – 1:15 p.m. ET. MITIGATE, the first randomized, double-blind, placebo-controlled study ever conducted in IgG4-RD, evaluated the safety and efficacy of CD19+ B-cell depletion with UPLIZNA.

Key findings include*:

• i. 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; seven of 68 participants receiving Uplizna experienced a flare compared to 40 of 67 participants receiving placebo.
• ii. A reduction in 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).
• iii. 57.4% (39 of 68) of participants receiving Uplizna achieved flare-free, treatment-free, complete remission at Week 52 compared to 22.4% (15 of 67) participants receiving placebo (p<0.001).
• iv.  58.8% (40 of 68) of participants receiving Uplizna achieved flare-free, corticosteroid-free, complete remission at Week 52 compared to 22.4% (15 of 67) participants receiving placebo (p<0.001).
• v.  Confirmation of the unique mechanism of action of Uplizna to deliver rapid and sustained depletion of peripheral B cells leading to lowered levels of disease biomarkers. Flares are indicative of high disease activity.

Notably, 89.7% (61 of 68) of Uplizna-treated patients required no glucocorticoid treatment for disease control during the placebo-controlled period, compared to 37.3% (25 of 67) of patients on placebo. After Week 8, Uplizna -treated patients experienced a ten-fold reduction in total glucocorticoid use relative to placebo.

The safety results in the placebo-controlled period were consistent with the established safety profile of Uplizna. The most common treatment-emergent adverse events included COVID-19, lymphopenia, urinary tract infection, and headache.

The data were simultaneously published in the New England Journal of Medicine. In August, the FDA  granted Breakthrough Therapy Designation for Uplizna in IgG4-RD based on data from the MITIGATE study, and regulatory filing activities are currently underway.

Citation: "Inebilizumab for Treatment of IgG4-Related Disease". Authors: John H. Stone, M.D., M.P.H., Arezou Khosroshahi, M.D., Wen Zhang, M.D., Ph.D., Emanuel Della Torre, M.D., Ph.D., Kazuichi Okazaki, M.D., Ph.D., Yoshiya Tanaka, M.D., Ph.D., J. Matthias Löhr, M.D., Ph.D., +17, for the MITIGATE Trial Investigators^*Published November 14, 2024DOI: 10.1056/NEJMoa2409712.