FDA Approves Uplizna for Chronic Inflammatory Condition IgG4-RD

The FDA has approved Uplizna (inebilizumab-cdon) as the first treatment for adults living with immunoglobulin G4-related disease (IgG4-RD), a chronic inflammatory condition that can affect multiple organs. The condition is characterized by periods of remission and unpredictable disease flares.

Uplizna is a monoclonal antibody that is already approved to treat neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease that affects the optic nerves and spinal cord. It has a wholesale acquisition cost of $140,248.50 per dose (3 vials). After two initial loading doses, patients receive Uplizna infusions every six months.

Amgen provides support, tools, and resources for patients and caregivers through Amgen By Your Side. Eligible commercially insured Uplizna patients may be eligible for a $0 copay through the Co-Pay assistance program.

IgG4-RD is typically treated with glucocorticoids (like prednisone) and, in some cases, B-cell-depleting therapies like rituximab. Research has found that the function of B cells—important immune cells—can lead to inflammation when dysregulated.

Uplizna is an engineered antibody therapy designed to precisely bind to and target B cells expressing the protein marker CD19+, including plasmablasts and some plasma cells.

John Stone, M.D.

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

The approval of Uplizna for IgG4-RD is supported by data from the MITIGATE trial, which demonstrated that the therapy decreased disease activity by reducing flares in patients while maintaining its efficacy and established safety profile.

The primary endpoint was time to first treated and adjudicated IgG4-RD flare.  The three key secondary endpoints were annualized flare rate; flare-free, treatment-free complete remission; and flare-free, corticosteroid-free complete remission.  The MITIGATE trial also includes an optional three-year open-label treatment period and a safety follow-up period.

The trial demonstrated an 87% reduction in the risk of IgG4-RD flare compared with placebo during the 52-week period; 10.3% (7 of 68) of participants receiving Uplizna experienced a flare compared with 59.7% (40 of 67) of participants receiving placebo.

Additionally, 57.4% (39 of 68) of participants receiving Uplizna achieved flare-free, treatment-free, and complete remission at week 52 compared with 22.4% (15 of 67) of participants receiving placebo, and 58.8% (40 of 68) of participants receiving Uplizna achieved flare-free, corticosteroid-free, and complete remission at week 52 compared with 22.4% (15 of 67) of participants receiving placebo.

Also, 99.7% (61 of 68) of Uplizna-treated patients required no glucocorticoid treatment for disease control during the placebo-controlled period, outside of the planned glucocorticoid tapering, compared with 37.3% (25 of 67) of patients on placebo.

The most common adverse reactions in patients with IgG4-RD treated with Uplizna were urinary tract infection (12%) and lymphopenia (19%).