FDA Expands Use of Amgen’s Uplizna to Include IGG4-Related Disease

Rare Daily Staff

The U.S. Food and Drug Administration expanded the approved use of Amgen’s Uplizna to include the treatment of adults living with immunoglobulin G4-related disease, the first and only treatment approved for the chronic and debilitating immune-mediated inflammatory condition.

The FDA granted Breakthrough Therapy designation to Uplizna for the treatment of IgG4-RD, recognizing the high unmet medical need and the potential for Uplizna to provide benefit to people with the condition.

Immunoglobulin G4-related disease (IgG4-RD) is a progressive disease that can affect a variety of organ systems and often affects multiple organs over time. It is characterized by periods of remission and unpredictable disease flares. IgG4-RD can cause permanent organ damage with or without the presence of symptoms. Awareness of how organ damage manifests is critically important to inform the timely diagnosis of IgG4-RD. B cells are central to the pathogenesis of IgG4-RD. 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. The typical age of onset of IgG4-RD is between 50 and 70 years old and, unlike many other immune-mediated diseases, IgG4-RD is more likely to occur in men than women.

Uplizna is a humanized monoclonal antibody that causes targeted and sustained depletion of key cells that contribute to underlying disease process (autoantibody-producing CD19+ B cells, including plasmablasts and some plasma cells). The precise mechanism by which Uplizna exerts its therapeutic effects in IgG4-RD is unknown. After two initial infusions, patients need one dose of Uplizna every six months.

The approval of Uplizna for IgG4-RD is supported by data from the MITIGATE trial, the first randomized, double-blind, placebo-controlled trial conducted in IgG4-RD. This trial demonstrated the potential of Uplizna to decrease disease activity by reducing flares in patients, while maintaining its efficacy and established safety profile.

IgG4-RD is the second approved indication for Uplizna, which the FDA previously approved for the treatment of adult patients with AQP4-IgG+ Neuromyelitis Optica Spectrum Disorder (NMOSD) in June 2020. The FDA also granted Orphan Drug designation for Uplizna for the treatment of generalized myasthenia gravis. Regulatory filing activities are underway for generalized myasthenia gravis, with submission anticipated to be complete in H1 2025.

“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, 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.”