HQ Team
April 4, 2025: Amgen Inc.’s treatment for adults living with immune-mediated inflammatory conditions was granted regulatory approval by the US Food and Drug Administration, according to a statement.
Uplizna, the treatment for Immunoglobulin G4-related disease (IgG4-RD), was given the nod under the Breakthrough Therapy Designation of the FDA.
“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.
Uplizna has a broader potential in other immune-mediated diseases, including neuromyelitis optica spectrum disorder and generalized myasthenia gravis, he said.
IgG4-RD can occur in multiple organs and lead to fibrosis and permanent organ damage. Understanding how organ damage manifests is important to the timely diagnosis of the disease.
Permanent organ damage
The disease mimics other diseases due to the heterogeneous and unpredictable inflammatory flares that can occur. Over time, IgG4-RD can affect virtually any organ system. Flares are times when the disease is more active, causing more inflammation. A flare can last from a few days to weeks.
IgG4-RD can cause permanent organ damage with or without the presence of symptoms. In IgG4-RD, CD19-expressing (CD19+) B cells are thought to drive inflammatory and fibrotic processes and interact with other immune cells that contribute to disease activity.
“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, MD, MPH, principal investigator, and a 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. 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.”
87% flare reduction
The approval of Uplizna for IgG4-RD was supported by data from a trial, which demonstrated the potential of the treatment to decrease disease activity by reducing flares in patients while maintaining its efficacy and established safety profile, according to the statement.
An 87% reduction in the risk of IgG4-RD flare compared to placebo was achieved during the trial compared to 59.7% in the placebo group. After 52 weeks of treatment, 57.4% of the patients had complete remission compared to 22.4% having a placebo.
This is the second approved indication for the treatment, which was previously approved by the FDA for the treatment of adult patients with AQP4-IgG+ Neuromyelitis Optica Spectrum Disorder in June 2020.
The FDA also granted Uplizna Orphan Drug Designation for the treatment of generalized myasthenia gravis. Regulatory filing activities are underway for gMG with submission anticipated to be complete in H1 2025.
Limited epidemiology data
The disease prevalence is estimated at 20,000 people in the US (5 in 100,000 worldwide), although the number of IgG4-RD patients is difficult to determine based on limited epidemiology data. The typical age of onset of IgG4-RD is between 50 and 70 years.
The Amgen treatment centres around a monoclonal antibody (mAb) that causes targeted and sustained depletion of key cells that contribute to the underlying disease process (autoantibody-producing CD19+ B cells, including plasmablasts and some plasma cells).
After two initial infusions, patients need one dose of Uplizna every six months.
