Amgen announced today that the U.S. Food and Drug Administration (FDA) has approved UPLIZNA (inebilizumab-cdon) as the first and only treatment for adults with Immunoglobulin G4-related disease (IgG4-RD), a chronic and debilitating immune-mediated inflammatory condition that can affect multiple organs.
The FDA granted Breakthrough Therapy Designation to UPLIZNA for IgG4-RD treatment, recognizing the high unmet medical need and the therapy's potential to benefit patients with this serious condition. This approval represents a significant milestone for patients who previously had no FDA-approved treatment options.
"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, M.D., executive vice president of Research and Development at Amgen.
Understanding IgG4-Related Disease
IgG4-RD is a progressive disease characterized by chronic inflammation that can affect virtually any organ system. The condition often affects multiple organs simultaneously and can lead to fibrosis and permanent organ damage if left untreated. The disease mimics other conditions due to heterogeneous and unpredictable inflammatory flares, making diagnosis challenging.
The prevalence is estimated at approximately 20,000 people in the United States (5 in 100,000 worldwide), though exact numbers are difficult to determine due to limited epidemiological data. Unlike many other immune-mediated diseases, IgG4-RD is more common in men than women, with typical onset between 50 and 70 years of age.
"Targeting CD19+ B cells with UPLIZNA has proven to be a highly effective approach to help address the pathophysiology of IgG4-RD," said John Stone, M.D., M.P.H., principal investigator, and professor of medicine at Harvard Medical School. "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."
Breakthrough Clinical Results
The approval is supported by data from the MITIGATE trial, the first randomized, double-blind, placebo-controlled study conducted in IgG4-RD. Key findings from the trial include:
- An 87% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.13, p<0.001)
- Only 10.3% of UPLIZNA-treated patients experienced a flare compared to 59.7% of those on placebo
- 58.8% of patients receiving UPLIZNA achieved flare-free, corticosteroid-free, and complete remission at Week 52 compared to 22.4% of patients on placebo
- 89.7% of UPLIZNA-treated patients required no glucocorticoid treatment for disease control during the placebo-controlled period
- UPLIZNA-treated patients experienced a ten-fold reduction in mean total glucocorticoid use compared to placebo (118 mg vs. 1385 mg)
The most common adverse reactions in patients with IgG4-RD treated with UPLIZNA (occurring in at least 10% of patients and greater than placebo) were urinary tract infection (12%) and lymphopenia (19%).
Mechanism of Action
UPLIZNA is a humanized monoclonal antibody that causes targeted and sustained depletion of CD19+ B cells, including plasmablasts and some plasma cells, which are key contributors to the underlying disease process. B cells are central to the pathogenesis of IgG4-RD, driving inflammatory and fibrotic processes and interacting with other immune cells that contribute to disease activity.
After two initial infusions, patients need one dose of UPLIZNA every six months, providing a convenient treatment schedule for chronic management of the condition.
Expanding Therapeutic Applications
This is the second approved indication for UPLIZNA, which was previously approved by the FDA for the treatment of adult patients with AQP4-IgG+ Neuromyelitis Optica Spectrum Disorder (NMOSD) in June 2020. The FDA has also granted UPLIZNA Orphan Drug Designation for the treatment of generalized myasthenia gravis (gMG), with regulatory filing anticipated in the first half of 2025.
"We are very proud of the journey that has led us to this approval for UPLIZNA, and deeply appreciate the physicians, patients, and families who have supported these efforts. This day is really a moment of hope for the IgG4-RD community," said Daniel Cimbora, PhD, Senior Scientific Director at Amgen.
Patient Support
Amgen is committed to supporting patients with IgG4-RD and helping appropriate patients access UPLIZNA. Patients and caregivers who need support, tools, or resources can contact Amgen By Your Side for assistance with treatment access and ongoing support.
Important Safety Information
UPLIZNA is contraindicated in patients with a history of life-threatening infusion reaction to UPLIZNA, active hepatitis B infection, or active or untreated latent tuberculosis.
The therapy carries warnings and precautions related to infusion reactions, infections, possible increased immunosuppressant effects when combined with other immunosuppressants, hepatitis B virus reactivation, progressive multifocal leukoencephalopathy, tuberculosis, vaccinations, reductions in immunoglobulins, and fetal risk.
Healthcare providers should perform appropriate screening before initiating treatment and monitor patients throughout therapy for potential adverse events.
