Zenas BioPharma reports new obexelimab data in IgG4-related disease, including long-term flare outcomes, reduced glucocorticoid toxicity, and vaccine responses.
Written By: Sravani Pamanji, PharmD
Reviewed By: Pharmacally Editorial Team
Zenas BioPharma has reported new clinical data on obexelimab, its investigational treatment for immunoglobulin G4-related disease (IgG4-RD). Presented at the 6th International Symposium on IgG4-Related Disease, held in Cambridge, Massachusetts, from October 8 to 10, 2026, the findings cover longer-term flare outcomes, glucocorticoid-associated toxicity and vaccine responses following a planned treatment-free period.
The analyses extend the clinical evidence from the Phase 3 INDIGO trial, although they differ in design and follow-up. The flare and vaccine findings come from the open-label extension (OLE), while the glucocorticoid-toxicity results compare obexelimab with placebo during the original 52-week randomized, controlled period.
Longer Term Follow Up Shows Sustain Flare Up
Patients who completed the initial 52-week randomized period could enter the OLE and receive obexelimab 250 mg by subcutaneous injection once weekly.
At the 12-month assessment, the estimated probability of remaining free of disease flares was 93% when flares requiring rescue treatment were confirmed by both investigators and an adjudication committee. Using investigator-determined flares requiring rescue treatment, the estimated probability was 87%. Five flare events were awaiting adjudication at the data cutoff.
The median cumulative glucocorticoid rescue dose during follow-up was 0 mg, while the mean was 105 mg. Adverse-event rates in the OLE were comparable to or lower than those recorded during the randomized period.
These findings provide additional information about disease control during continued treatment. However, the OLE lacks a concurrent placebo comparison, limiting conclusions about comparative efficacy over the longer term. The pending flare adjudications also warrant consideration when interpreting the estimates.
Randomized Data Show Lower Glucocorticoid-Associated Toxicity
Glucocorticoids remain important in managing IgG4-RD, but prolonged exposure can contribute to metabolic, cardiovascular, musculoskeletal and other complications. Reducing these treatment-related effects is therefore an important consideration in long-term disease management.
In a secondary analysis of the randomized INDIGO trial, researchers assessed glucocorticoid-associated toxicity using the Glucocorticoid Toxicity Index (GTI). At Week 52, obexelimab was associated with a significantly greater reduction in cumulative glucocorticoid toxicity than placebo. The between-group difference in the GTI Cumulative Worsening Score was −11.4 points (p=0.021).
Fewer patients receiving obexelimab also reached predefined thresholds for clinically meaningful worsening. A GTI Cumulative Worsening Score increase of at least 20 points occurred in 42.2% of obexelimab-treated patients versus 61.2% of placebo-treated patients. For an increase of at least 30 points, the respective proportions were 28.9% and 49.4%.
Unlike the OLE findings, these results come from a randomized, placebo-controlled comparison and provide stronger evidence of a treatment-associated difference during the first year. They support the potential steroid-sparing value of obexelimab, although the findings should not be interpreted as evidence that treatment eliminates glucocorticoid-related complications.
Vaccine Responses Following a Planned Treatment-Free Window
A separate OLE sub-study examined immune responses to influenza and COVID-19 vaccination during a planned treatment-free window.
Among the participants assessed, 6 of 7 (86%) developed seroimmunity to influenza, while all 4 assessed participants (100%) developed seroimmunity to COVID-19. No disease flares were reported during the treatment-free window, which lasted an average of 34.6 days.
The analysis also reported preservation of pre-existing immunity markers following long-term obexelimab treatment in 71% of participants assessed for influenza and 50% assessed for COVID-19.
These early observations suggest that vaccine responses can occur following a planned interruption of treatment. However, the sample was very small, and the findings do not establish vaccine effectiveness or demonstrate that immune responses are unaffected during continuous obexelimab treatment. The short observation period also limits conclusions about longer-term disease stability during treatment interruption.
Mechanism and Regulatory Status
Obexelimab is a bifunctional monoclonal antibody designed to bind CD19 and FcγRIIb, inhibiting B-cell activity without depleting B cells. This approach is intended to modulate immune activity implicated in autoimmune disease.
The investigational treatment has been evaluated in nine clinical trials involving 667 participants, according to Zenas. In August 2026, the US Food and Drug Administration accepted the company’s biologics license application (BLA) for obexelimab in IgG4-RD and set a target action date of May 27, 2027. The treatment has not yet been approved for this indication.
Zenas is also evaluating obexelimab in the Phase 2 SunStone trial in systemic lupus erythematosus, with topline results expected in the fourth quarter of 2026.
Clinical Interpretation
The three analyses contribute different levels of evidence to obexelimab’s clinical evaluation in IgG4-RD. The randomized glucocorticoid-toxicity analysis provides comparative evidence that treatment may reduce the burden associated with glucocorticoid exposure during the first year. The open-label extension flare estimates extend the evidence on disease control, but the absence of a concurrent control group limits conclusions about comparative long-term efficacy. Meanwhile, the vaccine sub-study offers preliminary evidence of antibody responses following vaccination during a planned treatment-free period, although its small sample prevents broader conclusions about immune responses.
Taken together, the findings address important aspects of long-term IgG4-RD management beyond flare control alone. However, the magnitude and durability of these potential benefits, and their relevance to routine clinical practice, remain to be established. The FDA’s ongoing review will provide a further regulatory milestone in determining obexelimab’s potential role in IgG4-RD treatment.
Reference
Zenas BioPharma Announces the Presentation of New Obexelimab Data in IgG4-Related Disease at the 6th International Symposium on IgG4-Related Disease, Zenas Biopharma, 12 October 2026
A Phase 3 Study of Obexelimab in Patients with IgG4-Related Disease (INDIGO), ClinicalTrials.gov ID NCT05662241
About the Writer
Sravani Pamanji is a PharmD (LinkedIn) professional with experience in scientific writing, medical literature review, drug profile preparation, and clinical case documentation. She has contributed to scientific publication and presented at the 74th Indian Pharmaceutical Congress. Her training includes ICH GCP E6(R3), scientific research, and medication safety. She is passionate about evidence-based medical communication and accurate dissemination of clinical and pharmaceutical information.