Uplizna Approved to Treat IgG4-Related Disease

Amgen’s UPLIZNA has been approved by the U.S. Food and Drug Administration as the first and only treatment for adults living with Immunoglobulin G4-related disease (IgG4-RD), a chronic and debilitating immune-mediated inflammatory condition that can affect multiple organs.

Approval is supported by data from the MITIGATE trial, the first randomized, double-blind, placebo-controlled trial conducted in IgG4-RD, which demonstrated the potential of UPLIZNA to decrease disease activity by reducing flares in patients, while maintaining its efficacy and established safety profile. The primary endpoint was time to first treated and adjudicated IgG4-RD flare. The three key secondary endpoints were annualized flare rate; flare-free, treatment-free complete remission; and flare-free, corticosteroid-free complete remission. The MITIGATE trial also includes an optional three-year open-label treatment period and a safety follow-up period after UPLIZNA discontinuation of up to two years.

Key findings from the trial include:

• An 87 percent reduction in the risk of IgG4-RD flare, compared to placebo, during the 52-week placebo-controlled period; 10.3 percent (seven of 68) of participants receiving UPLIZNA experienced a flare, compared to 59.7 percent (40 of 67) of participants receiving placebo.
• 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.
• 57.4 percent (39 of 68) of participants receiving UPLIZNA achieved flare-free, treatment-free and complete remission at Week 52, compared to 22.4 percent (15 of 67) of participants receiving placebo.
• 58.8 percent (40 of 68) of participants receiving UPLIZNA achieved flare-free, corticosteroid-free and complete remission at Week 52, compared to 22.4 percent (15 of 67) of participants receiving placebo.
• 89.7 percent (61 of 68) of UPLIZNA-treated patients required no glucocorticoid treatment for disease control during the placebo-controlled period, outside of the planned glucocorticoid tapering, compared to 37.3 percent (25 of 67) of patients on placebo.
• UPLIZNA-treated patients experienced a 10-fold reduction in mean total glucocorticoid use for disease control per patient relative to placebo (118 mg vs. 1,385 mg, respectively) during the placebo-controlled period.

The most common adverse reactions in patients with IgG4-RD (at least 10 percent of patients treated with UPLIZNA and greater than placebo) were urinary tract infection (12 percent) and lymphopenia (19 percent).

“The FDA approval of UPLIZNA marks a significant turning point for IgG4-RD patients and physicians who now have a proven treatment that targets a key driver of the disease, reducing the risk of flares and reliance on harmful long-term steroid use,” said Jay Bradner, MD, executive vice president of research and development at Amgen. “We are proud to deliver a therapy that has the potential to significantly improve care for patients with IgG4-RD and remain encouraged by UPLIZNA’s broader potential in other immune-mediated diseases, including neuromyelitis optica spectrum disorder and generalized myasthenia gravis. This approval underscores Amgen’s ongoing commitment and leadership in developing innovative treatments targeting CD19+ B-cells across multiple therapeutic areas.”