Uplizna: the first targeted drug approved to treat IgG4-related diseases

Amgen announced on 20254 month3 that Uplizna (i Nebilizumab-cdon) has been approved by the US FDA and has become the first drug to treat immunoglobulin G4-related diseases (IgG4-RD). Previously, Uplizna had obtained the FDA approval in 2020 Approved for the treatment of AQP4-IgG+neuromyelitis optica spectrum disorder (NMOSD). The newly approved indication makes Uplizna a breakthrough medicine for the treatment of IgG4-RD, helping to treat this chronic immune-mediated fibrotic disease. In addition, Uplizna has also made positive progress in the treatment of generalized myasthenia gravis (gMG). gMG’s third phase clinical trial results are also very promising, and regulatory filing for this indication is expected to be completed in the first half of 2025.

IgG4-RDThe pathogenesis and therapeutic targets

IgG4-RD is an immune fibrotic disease that affects multiple organs, may lead to irreversible organ damage, and is highly clinically heterogeneous. B cells play a key role in the pathogenesis of the disease, especially CD19 expressing B cells, which are thought to be the main drivers of inflammation and fibrosis. Uplizna is a humanized monoclonal antibody that targets and depletes these CD19+ B cells and prevents them from participating in the immune response, thereby reducing inflammation caused by immune dysregulation. This mechanism of action makes it potentially useful in the treatment of IgG4-RD, although its exact therapeutic mechanism is still under investigation.

MITIGATETrial: Efficacy and Safety Data for Uplizna

Uplizna was approved by the FDA based on its performance in the MITIGATE trial. This is the first randomized, double-blind, placebo-controlled trial to evaluate the effectiveness of Uplizna in reducing the risk of flares in patients with IgG4-RD. The trial results show that Uplizna can significantly reduce the patient's risk of exacerbation (87%) compared with the placebo group, and the annual exacerbation rate is reduced from 0.71 in the placebo group to 0.10 in the treatment group. What's more, nearly 60% of patients treated with Uplizna were seizure-free, treatment-free, or in complete remission by week 52, compared with 22.4% of patients in the placebo group. These results provide strong evidence of the efficacy of Uplizna in the treatment of IgG4-RD.

UpliznaSafety and Side Effects

AlthoughUplizna is highly effective, patients still need to be concerned about some side effects when using the drug. According to the results of the MITIGATE trial, the most common adverse reactions were urinary tract infection (12%) and lymphopenia (19%). In addition, patients in the treatment group significantly reduced the use of glucocorticoids in the process of controlling the disease, indicating that Uplizna is not only better than placebo in efficacy, but also helps reduce dependence on glucocorticoids. Generally speaking, Uplizna is safe, but it needs to be used under the guidance of a doctor to ensure the patient's health and maximize the treatment effect.

Through the launch of Uplizna, patients are expected to improve the treatment prospects of IgG4-RD through this targeted therapy, reduce symptoms, avoid organ damage, and significantly improve the quality of life.

References:

Amgen presents new data across rare inflammatory diseases at ACR 2024. https://www.amgen.com/newsroom/press-releases/2024/11/amgen-presents-new-data-across-rare-inflammatory-diseases-at-acr-2024. Published Nov. 14, 2024. Accessed April 3, 2025.