Stanford Medicine researchers and their colleagues found that a new drug, obexelimab, significantly reduces the risk of relapse in patients with IgG4-related disease, a rare chronic immune condition often misdiagnosed as cancer.
People with IgG4-related disease can develop severe inflammation and fibrosis, or thickening of connective tissue, that leads to tumor-like masses throughout their bodies. They are often treated with drugs that eliminate B cells, which are a critical component of a healthy immune system, but in patients with IgG4-related disease are overactive and misdirected. Eliminating these cells can leave patients vulnerable to infections. Obexelimab instead inhibits B cell function without destroying them.
In an international trial published June 2 in the New England Journal of Medicine , patients who received obexelimab experienced half the risk of a disease relapse compared with patients who received placebo.
“Patients with IgG4-related disease can spend years pursuing a diagnosis while their organs are being damaged; even then, the treatment options have been limited,” said Matthew Baker , MD, an associate professor of immunology and rheumatology and a co-first author of the study. “Having something that works this well, and may be safer than what is currently available, is a real step forward.”
The other co-first author of the paper is Emanuel Della-Torre of Vita-Salute San Raffaele University. The senior authors are John Stone of Massachusetts General Brigham and Emma Culver of University of Oxford.
Focusing on B cells
IgG4-related disease is estimated to affect between 10,000 and 30,000 people in the United States, although clinicians like Baker suspect the true number may be higher given how often it is misdiagnosed. It is only in the last 25 years that the disease has been formally recognized and understood to be linked to elevated levels of IgG4 antibodies in the blood.
People with IgG4-related disease commonly develop swelling in their pancreas, salivary glands, kidneys, lymph nodes and other parts of the body. The soft tissue masses can closely resemble cancer, frequently resulting in invasive biopsies or surgery before the correct diagnosis is made.
Researchers have shown that the disease is fundamentally driven by B cells, which begin to attack the body’s own tissues, leading to inflammation and fibrosis.
To treat the disease, doctors currently turn to drugs that eliminate B cells, including inebilizumab, approved in 2025, and rituximab — which is approved to treat certain cancers and autoimmune diseases but is used off-label for IgG4-related disease. Both B-cell-depleting therapies are highly effective, but long-term use can be associated with serious infections.
“We know that when we eliminate B cells, the disease gets better,” Baker said, “but if a patient gets an infection while on a B-cell-depleting drug, their body cannot as effectively fight that infection, and unlike other drugs that can be stopped, the effects of these therapies last many months.”
Obexelimab, developed by Zenas BioPharma to treat a variety of immune diseases, takes a different approach: It also binds to a marker specific for B cells, but instead of marking those cells for destruction, the other portion of the molecule binds to an inhibitory receptor on B cells, effectively turning off the activity of the cell.
Encouraging results
For the study, researchers enrolled 194 patients with IgG4-related disease at 114 sites in 19 countries. All participants initially received steroids to induce remission of their IgG4-related disease. They were then randomly assigned to receive weekly subcutaneous injections of obexelimab or a placebo for 52 weeks. At the same time, steroids were tapered and stopped during the first eight weeks of the trial.
The researchers found that 26.8% of patients had a relapse in the obexelimab group, compared with 54.6% in the placebo group. Patients treated with obexelimab were also nearly twice as likely to be in complete remission after one year (37.1% versus 19.6%), with no signs of active disease, and they needed less emergency steroid treatment over the course of the study.
“This drug will be a really nice option for a subset of patients,” Baker said. “For many patients with mild to moderate disease, this drug will likely be effective and may have safety advantages.”
He suspects the drug, if approved by the U.S. Food and Drug Administration, will be most useful in people who have IgG4-related disease that isn’t life threatening, such as people who have enlarged salivary glands, tear glands and lymph nodes. For those patients with masses causing blockages in the bile ducts or kidneys, more aggressive and potentially potent approaches may still be needed.
Baker has focused much of his career on IgG4-related diseases: He has built Stanford Medicine’s IgG4-related disease clinic into one of the largest in the country, caring for more than 300 patients over the past decade. He is also leading an investigator-initiated trial at Stanford Medicine of efgartigimod, a drug that facilitates antibody degradation, rather than targeting B cells directly.
“A decade ago, patients had very limited options,” Baker said. “Now we have multiple effective treatments and more in development. It’s an extremely exciting time for the field and for patients.”
See the journal article for a complete list of co-authors and their institutions.
Zenas BioPharma sponsored the research.
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New England Journal of Medicine
Randomized controlled/clinical trial
People
Obexelimab for the Treatment of IgG4-Related Disease
2-Jun-2026