Zenas Reports Positive Results in IgG4‑RD Trial

Zenas Reports Positive Results in IgG4‑RD Trial to Date

A drug designed to calm, rather than broadly suppress, immune cells has passed a key test in treating a challenging and rare autoimmune condition.

Zenas BioPharma’s antibody obexelimab sharply cut disease flare‑ups and reduced reliance on steroids in people with immunoglobulin G4–related disease (IgG4‑RD), according to results from the phase 3 INDIGO trial presented this week at the European rheumatology meeting EULAR 2026 and published in the New England Journal of Medicine.

IgG4‑RD is a chronic fibroinflammatory disease that can affect almost any organ system. It commonly involves the pancreas, bile ducts, kidneys, lungs, and salivary and tear glands, and many patients have permanent organ damage by the time they are diagnosed.

Obexelimab is given as a weekly injection that patients or caregivers can administer at home, in contrast to some existing B‑cell–targeting therapies that require periodic intravenous infusions in hospital settings.

Rather than depleting B cells for months at a time, obexelimab takes a more nuanced approach, binding to two targets on B‑lineage cells—CD19 and an inhibitory receptor called FcγRIIb—to dial down their activity without wiping them out. In the trial, patients’ B‑cell counts dipped but stayed within the normal range and appeared to stabilize over time, a pattern researchers hope may translate into fewer long‑term risks such as severe infections or poor vaccine responses that can accompany prolonged B‑cell depletion.

In the global study, 194 adults with active IgG4‑RD were randomly assigned to receive weekly injections of obexelimab or placebo for a year. Everyone first received a short course of standard steroid treatment, which was tapered off by week eight, mimicking how patients are often managed in the real world. Over the following 52 weeks, patients on obexelimab were 56 percent less likely to experience a disease flare that required “rescue” treatment than those on placebo, and nearly three‑quarters of obexelimab‑treated patients remained flare‑free at one year, versus under half in the placebo group.

The treatment effect went beyond simply delaying flares. Obexelimab patients needed far less additional steroid medication over the year—about one‑third as much as those on placebo—and were more likely to reach complete remission, defined as no active disease and no flare treatment at week 52.

Almost all patients in both arms reported some side effects, but serious events and severe (grade 3 or higher) problems were actually less common with obexelimab than with placebo in the trial. Infections occurred at similar or slightly lower rates on the drug.

Zenas submitted a Biologics License Application to the U.S. Food and Drug Administration for obexelimab in IgG4‑RD in May and is continuing to follow patients in a three‑year extension study to gauge how durable the benefits are and how the safety profile evolves over time.

The company is also testing the same strategy in other autoimmune diseases, including systemic lupus and multiple sclerosis, suggesting the INDIGO results may be a preview of a broader shift toward “immune calming” approaches in complex immune‑mediated conditions.

“Physicians currently have very few treatment options for patients living with this chronic, progressive and debilitating disease,” said Emanuel Della Torre, associate professor of medicine at Vita‑Salute San Raffaele University in Milan, Italy. “The phase 3 INDIGO data indicate obexelimab could offer a novel, highly active, self‑administered therapy for people living with IgG4‑RD, one that has the potential to avoid the safety concerns associated with chronic steroid use and long‑term B‑cell depletion.”