New Phase 3 data highlight obexelimab’s role in IgG4-RD care
Weekly injections reduced flares and helped maintain disease control
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Obexelimab, Zenas Biopharma’s experimental, self-administered injectable therapy, reduced the risk of disease flares in adults with immunoglobulin G4-related disease (IgG4-RD), according to new Phase 3 trial results.
The findings come from top-line results presented by the company from the global Phase 3 INDIGO clinical trial (NCT05662241), which compared obexelimab with a placebo over one year in nearly 200 adults with active IgG4-RD who required treatment with standard glucocorticoids.
“Given obexelimab’s significant clinical activity and the compelling safety and tolerability profile observed in the INDIGO trial, we believe obexelimab may have an important role as a first-line therapy in the long-term management of IgG4-RD,” Lonnie Moulder, founder and CEO of Zenas, said in a company press release.
Company plans regulatory filings after trial meets main goal
Because the trial met its primary goal of delaying flares compared with placebo, Zenas Biopharma plans to submit applications to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) seeking approval of obexelimab for IgG4-RD.
“We look forward to submitting our Biologics License Application to the FDA in the second quarter [April to June] of 2026 and our Marketing Authorization Application to the EMA in the second half of this year,” Moulder said.
Complete data from INDIGO are expected to be presented at a future medical meeting.
In IgG4-RD, plasmablasts, a mature form of immune B-cells, accumulate in tissues and produce large amounts of an antibody called IgG4. B-cells and plasmablasts drive the inflammation and tissue scarring that characterize IgG4-RD and are thought to play a major role in disease flares.
Patients living with IgG4-RD have faced limited treatment choices for far too long.
Glucocorticoids are typically used as first-line IgG4-RD treatment. Other immunosuppressive agents may be added to reduce reliance on glucocorticoids, whose long-term use can cause serious side effects. Uplizna (inebilizumab-cdon), the only approved therapy for IgG4-RD in the U.S., is an into-the-vein infusion therapy designed to deplete B-cells.
Obexelimab is an antibody-based therapy given by under-the-skin, or subcutaneous injection. It selectively targets two proteins on the surface of B-cells: CD19 and FCGR2B.
Because these proteins help regulate how B-cells produce antibodies and inflammatory signals, the experimental therapy is expected to dampen the activity of several B-cell populations, including plasmablasts. This may help reduce disease activity and the risk of flares in IgG4-RD.
“Patients living with IgG4-RD have faced limited treatment choices for far too long,” said John Stone, MD, professor of medicine at Harvard Medical School and the Massachusetts General Hospital. “[Obexelimab’s] intriguing mechanism of action — emphasizing B-cell inhibition [suppression] rather than B-cell depletion — and self-administration by patients, may be an important new therapy for people living with IgG4-RD.”
Earlier trial showed signs of benefit in IgG4-RD
A previous Phase 2 trial (NCT02725476) found that intravenous infusions of obexelimab given every other week for about six months were associated with reduced disease severity in all but one of the 15 adults with IgG4-RD who took part. More than half (53%) achieved complete remission, as defined by the study, without the need for glucocorticoids.
The Phase 3 INDIGO study enrolled 194 adults with active IgG4-RD requiring glucocorticoid treatment, who were randomly assigned to receive weekly subcutaneous injections of either obexelimab or a placebo for one year.
Participants had a mean age of 59.6 years, and 67% were men. In most patients (94%), the disease affected two or more organs.
The study’s main goal was to determine whether obexelimab could significantly delay the time to a first flare requiring glucocorticoid-based rescue therapy, as determined by investigators and an adjudication committee.
Results showed that a significantly lower proportion of obexelimab-treated patients experienced a flare compared with those receiving placebo (26.8% vs. 54.6%), corresponding to a 56% reduction in flare risk.
Secondary findings point to fewer flares and less rescue treatment
In secondary analyses, obexelimab was found to significantly prolong the time to first investigator-determined flare requiring rescue therapy and to significantly reduce the number of flares requiring rescue treatment and overall use of rescue therapy, compared with placebo.
Obexelimab was also associated with a significantly higher proportion of patients achieving complete remission, as defined by the study. Overall, 73% of people treated with obexelimab did not experience a flare during the study period.
The therapy was well tolerated, with no new safety signals reported. Overall infection rates were lower with obexelimab than with placebo, while injection-site reactions were similar between treatment groups.
Participants who completed the placebo-controlled portion of the trial may enter an open-label extension, during which all participants will receive obexelimab for up to three years.
“The INDIGO trial results are supported by the largest body of clinical data ever reported in this indication,” said Lisa von Moltke, MD, head of research and development and chief medical officer of Zenas. “On behalf of the Zenas team, I would like to thank the patients and healthcare professionals who took part in the INDIGO trial.”
The company is also studying obexelimab as a potential treatment for other autoimmune diseases linked to abnormal B-cell activity, including lupus and multiple sclerosis, with Phase 2 trials ongoing.
Zenas has partnered with Bristol Myers Squibb, which holds exclusive development and commercialization rights for obexelimab in the Asia-Pacific region, including Japan, South Korea, Taiwan, Hong Kong, Singapore, and Australia.
