Inebilizumab FDA Approved as First Treatment for IgG4-RD

Inebilizumab-cdon (Uplizna; Amgen) was approved as the first and only treatment for immunoglobulin G4–related disease (IgG4-RD), a chronic and debilitating immune-mediated inflammatory condition, Amgen announced in a press release.¹

The approval was supported by data from the randomized, double-blind, placebo-controlled MITIGATE trial (NCT04540497), which was the first of its kind to evaluate a treatment for IgG4-RD. Inebilizumab targets and depletes CD19+ B cells, which are thought to drive inflammation and fibrosis directly via cytokines or indirectly by activating pathogenic T cells.²

In the MITIGATE trial, inebilizumab reduced the risk of flares of IgG4-related disease at 1 year, with 10% of patients in the inebilizumab cohort experiencing at least 1 flare vs 60% in the placebo group (HR, 0.13; 95% CI, 0.06-0.28; P < .001). The annualized flare rate was also lower in the inebilizumab cohort, with a rate ratio of 0.14 (95% CI, 0.06-0.31; P < .001).

In the MITIGATE trial, inebilizumab reduced the risk of flares of IgG4-related disease at 1 year. | Image credit : Olivier Le Moal - stock.adobe.com

Flare-free, treatment-free complete remission also occurred more frequently in the inebilizumab group (OR, 4.68; 95% CI, 2.21-9.91; P < .001), as did flare-free, glucocorticoid-free complete remission (OR, 4.96; 95% CI, 2.34-10.52; P < .001).

"Targeting CD19+ B cells with [inebilizumab] has proven to be a highly effective approach to help address the pathophysiology of IgG4-RD," John Stone, MD, MPH, principal investigator, a professor of medicine at Harvard Medical School, and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, said in a statement.¹ "The clinical community now has an FDA-approved therapeutic innovation for patients that targets underlying disease mechanisms and helps to control disease activity by reducing flares in IgG4-RD. Now, our work begins in raising awareness of this disease so that patients can access the right treatment as early as possible, avoiding a long and often harmful diagnostic journey."

IgG4-RD can lead to fibrosis and permanent organ damage, and it can affect any organ system over time. The heterogeneous and unpredictable inflammatory flares that patients experience mimic the symptoms of other diseases, and understanding the mechanisms of organ damage is crucial to timely diagnosis.

A total of 135 participants were randomized in the MITIGATE trial, with 68 receiving inebilizumab and 67 receiving a placebo.² Twelve participants (18%) in the inebilizumab group and 6 (9%) in the placebo group experienced serious adverse events (AEs) of grade 3 or higher during the treatment period, and no serious AE occurred in more than 1 patient. Six patients (9%) in the inebilizumab group and 3 patients (4%) in the placebo group withdrew from the study due to AEs.

The approval of inebilizumab for IgG4-RD comes after the FDA granted breakthrough therapy designation in this patient population due to a substantial unmet need for treatments.¹ Inebilizumab is also approved for the treatment of adult patients with AQP4-IgG+ neuromyelitis optica spectrum disorder, and it was granted orphan drug designation for the treatment of generalized myasthenia gravis.

"The FDA approval of [inebilizumab] 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," Jay Bradner, MD, executive vice president of research and development at Amgen, said in a statement.¹ "We are proud to deliver a therapy that has the potential to significantly improve care for patients with IgG4-RD and remain encouraged by [inebilizumab]'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."

References

1. Uplizna (inebilizumab-cdon) is now the first and only FDA-approved treatment for IgG4-related disease. News release. Amgen; April 3, 2025. Accessed April 3, 2025. https://www.amgen.com/newsroom/press-releases/2025/04/uplizna-inebilizumabcdon-is-now-the-first-and-only-fdaapproved-treatment-for-igg4related-disease

2. Stone JH, Khosroshahi A, Zhang W, et al. Inebilizumab for treatment of IgG4-related disease. N Engl J Med. 2025;392(12):1168-1177. doi:10.1056/NEJMoa2409712