INDIGO: Obexelimab Sustains IgG4-RD Flare Control, With John Stone, MD, MPH

Continued obexelimab maintained low flare rates and minimal glucocorticoid rescue in patients with IgG4-related disease (IgG4-RD) in the open-label extension of the phase 3 INDIGO trial, with a 12-month flare-free probability of 0.93.¹ John H. Stone, MD, MPH, professor of medicine at Harvard Medical School, the Edward A. Fox Chair in Medicine at Massachusetts General Hospital, and founding executive chairman of the IgG4ward Foundation, discussed the findings in an interview.

Stone presented the late-breaking data at the ACR Convergence 2026, held November 6-11 in Orlando, Florida. In the 52-week randomized period of INDIGO, obexelimab reduced flare risk by 56% versus placebo with a glucocorticoid taper (hazard ratio, 0.44; 95% CI, 0.28–0.71; P < .001).² Patients completing the randomized period could receive obexelimab 250 mg subcutaneously weekly in the extension, which included 113 patients in the efficacy population and 157 in the safety population, with a median follow-up of 10.0 months.¹

“So the efficacy in the open-label extension seems even better, if anything, compared to the phase 3 trial. And to keep patients flare-free means that they are free of risk from damage from the disease, free of risk from additional damage from steroid use or other immunosuppressive use,” Stone said.

Investigator- and adjudication committee-determined flares occurred in 6 of 113 patients (5.3%), with a 12-month flare-free probability of 0.93 (95% CI, 0.84–0.97), or 0.87 (95% CI, 0.77–0.93) for flares requiring rescue therapy.¹ Median cumulative glucocorticoid rescue was 0 mg, with a mean of 104.7 mg (standard deviation [SD], 473.6). Five investigator-determined flares remained pending adjudication.

Stone said obexelimab binds CD19 and FcγRIIb, the inhibitory Fc receptor on B cells, to inhibit rather than deplete them, with B cells returning to near-normal levels within weeks of stopping and preserved vaccine responses reported. He said the randomized period showed lower cumulative glucocorticoid toxicity and fewer herpes zoster reactivations with obexelimab. In the extension, upper respiratory infection (15.3%) and nasopharyngitis (12.1%) were the most common adverse events, serious adverse events occurred in 7.0%, and no deaths were reported; these open-label data have not been peer reviewed.

Relevant disclosures include AcepodiaBio, Amgen, Argenx, hingeBio, Novartis, Q32Bio, Sanofi, Zenas BioPharma, and ZipBio.

References

1. Stone J, Baker M, Della Torre E, et al. Durable disease control with obexelimab in IgG4-related disease: phase 3 INDIGO open-label extension. Abstract LB18. Presented at: ACR Convergence 2026; November 6-11, 2026; Orlando, FL.

2. Della-Torre E, et al; INDIGO Trial Investigators. Obexelimab for the treatment of IgG4-related disease. N Engl J Med. Published online June 2, 2026. doi:10.1056/NEJMoa2601337