Obexelimab lowered flare risk and steroid exposure in IgG4-related disease

Obexelimab treatment was associated with a lower risk of disease flare and reduced glucocorticoid exposure among patients with active IgG4-related disease, according to findings from the phase 3 INDIGO trial published in New England Journal of Medicine.

IgG4-related disease is a chronic fibroinflammatory condition that can involve nearly any organ system. The authors noted that glucocorticoid therapy is a cornerstone of treatment but is limited by toxic effects, and relapse after discontinuation is common. Obexelimab is a bifunctional monoclonal antibody designed to inhibit B-cell activity through coengagement of CD19 and FcγRIIb without inducing B-cell depletion. Obexelimab is being developed by Zenas BioPharma.

The double-blind, randomized, placebo-controlled trial enrolled 194 patients with active IgG4-related disease. Participants were randomly assigned to receive subcutaneous obexelimab 250mg or placebo once weekly for 52 weeks, with 97 patients assigned to each group. In both groups, glucocorticoids were tapered on a standardized schedule to discontinuation at week 8.

The primary end point was time to first IgG4-related disease flare requiring rescue therapy, as determined by both the investigator and an independent adjudication committee. Time to first flare was significantly longer with obexelimab than placebo, with a hazard ratio of 0.44 (95% CI, 0.28-0.71; P<0.001). Flares were reported in 26 patients (26.8%) in the obexelimab group and 53 patients (54.6%) in the placebo group.

Obexelimab also showed significant benefit across key secondary endpoints, including complete remission at week 52 (37.1% vs 19.6%; P=0.005) and cumulative glucocorticoid rescue therapy dose through week 52 (329.5mg vs 929.8mg; P=0.004). Serious adverse events occurred in 10.3% of patients receiving obexelimab and 18.6% receiving placebo. The authors concluded that weekly obexelimab led to a significantly lower risk of disease flare and significantly less glucocorticoid exposure than placebo.

Sources: Della-Torre E, Baker MC, Zhang W, et al. Obexelimab for the treatment of IgG4-related disease. N Engl J Med. Published online June 2, 2026. doi:10.1056/NEJMoa2601337

National Library of Medicine. Obexelimab for the treatment of IgG4-related disease. PubMed. Accessed July 6, 2026. https://pubmed.ncbi.nlm.nih.gov/42233621/