FDA Approves Inebilizumab (Uplizna) as First IgG4-RD Therapy for Adults

The US Food and Drug Administration (FDA) has approved inebilizumab-cdon (UPLIZNA®) as the first and only treatment for adult patients diagnosed with immunoglobulin G4-related disease (IgG4-RD).1

Announced by Amgen on April 3, 2025, the FDA previously designated inebilizumab as a Breakthrough Therapy for those with IgG4-RD, citing the significant unmet medical need and the potential impact of this treatment for patients. IgG4-RD is a chronic, immune-mediated inflammatory disorder that can be irreversibly damaging and can impact multiple organs.

“Targeting CD19+ B cells with UPLIZNA has proven to be a highly effective approach to help address the pathophysiology of IgG4-RD," John Stone, MD, MPH, principal investigator, and a professor of medicine at Harvard Medical School and Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, said in a statement. "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.”1

Inebilizumab was designed as a humanized monoclonal antibody (mAb) that can work to selectively and persistently deplete CD19+ B cells among patients with IgG4-RD, including depleting plasmablasts and certain plasma cells implicated in the processes of this condition. Although IgG4-RD’s precise mechanism of action is still unknown, treatment involves 2 initial infusions followed by maintenance dosing on an every-6-month basis.

Inebilizumab’s FDA approval was based on positive findings from the MITIGATE trial, designed as the first randomized, double-blind, placebo-controlled study in IgG4-RD.2 MITIGATE assessed the medication’s effectiveness and safety in the reduction of disease flares in adult subjects living with IgG4-RD.

The study's primary endpoint was designated as the time to first adjudicated and treated IgG4-RD flare. The MITIGATE trial program also involved an optional 3-year open-label extension and a safety follow-up of up to 2 years in the post-discontinuation phase.2

Overall, the study’s findings suggested that inebilizumab lowers disease activity while maintaining its established safety profile. Some notable findings include the drug’s risk reduction for IgG4-RD flares by 87% compared to placebo (HR: 0.13, P <.001) over the 52-week placebo-controlled period.1

Trial investigators found flare occurrences in 10.3% of the 68 inebilizumab-treated participants compared with 59.7% of the 67 subjects in the placebo arm. Furthermore, annualized flare rates among those treated were .10 versus .71 among those in the placebo group (P <.001).1

Other findings from MITIGATE demonstrated that 57.4% of those on inebilizumab attained flare-free, treatment-free complete remission at the 52-week mark, compared with only 22.4% of those placed in the placebo arm (P <.001). Additionally, it was noted that 58.8% attained flare-free, corticosteroid-free complete remission by the 52-week mark versus 22.4%, respectively (P <.001).1

Assessment of safety and the most commonly reported adverse events among those with IgG4-RD receiving the medication (≥10% incidence and greater than placebo) showed urinary tract infections (12%) and lymphopenia (19%).1,2

This approval by the FDA marks inebilizumab’s second approved indication, following its 2020 approval for adult patients with AQP4-IgG+ Neuromyelitis Optica Spectrum Disorder (NMOSD).1

“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,” Stone noted in his statement.1

References

1. Uplizna (INEBILIZUMAB-CDON) Is Now the First and Only FDA-Approved Treatment For Igg4-Related Disease. Amgen. 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. Amgen announces positive results for phase 3 registrational trial evaluating UPLIZNA® (inebilizumab-CDON) for treatment of immunoglobulin G4-related disease (igg4-RD). Amgen. June 5, 2024. Accessed April 3, 2025. https://wwwext.amgen.com/newsroom/press-releases/2024/06/amgen-announces-positive-results-for-phase-3-registrational-trial-evaluating-uplizna-inebilizumabcdon-for-treatment-of-immunoglobulin-g4related-disease-igg4rd.