JASMINE Data Support FcRn Blockade in SLE, With Richard Furie, MD

Autoantibodies drive tissue injury in systemic lupus erythematosus (SLE) through several mechanisms, but none of the approved therapies target circulating IgG directly. In the phase 2 JASMINE trial, nipocalimab tested whether blocking the neonatal Fc receptor (FcRn) could reduce those antibodies and lower disease activity.

At American College of Rheumatology (ACR) Convergence 2026 in Orlando, Florida, Richard Furie, MD, chief of the Division of Rheumatology at Northwell Health and professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, went over the JASMINE findings in an interview with HCPLive.

How FcRn Blockade With Nipocalimab Lowers IgG Autoantibodies

The body normally recycles IgG through FcRn. In the acidic endosome, IgG binds to the receptor. When the endosome reaches the cell surface, the neutral pH releases it back into circulation. This salvage pathway gives IgG its long half life, and it applies to protective antibodies and pathogenic autoantibodies alike.

“If one develops an antibody against the neonatal Fc receptor and blocks it, you’re basically blocking that salvage pathway, and you can shunt IgG, both protective and autoantibodies, towards degradation,” Furie said.

In lupus, IgG autoantibodies can cause direct cell death and form immune complexes. They can also cause tissue damage through antibody-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity.

JASMINE Trial Design in Active SLE

JASMINE enrolled 228 adults with active, moderate to severe SLE. They were randomly assigned to intravenous nipocalimab 5 mg/kg, nipocalimab 15 mg/kg, or placebo every 2 weeks through week 52, on top of background therapy.¹ The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 24.

The entry criteria resembled those of other lupus trials: a SLEDAI score ≥6 with ≥1 BILAG A or ≥2 BILAG B scores. Furie pointed to one stricter requirement. Patients enrolled because of rash needed a CLASI activity score ≥6, and patients enrolled because of arthritis needed ≥4 active joints, each both swollen and tender.

Nipocalimab SRI-4 Response Grew From Week 24 to Week 52

The 15 mg/kg dose met the primary endpoint, with an SRI-4 response rate of 53.5% vs 46.7% for placebo at week 24.¹ Furie described that roughly 7 percentage point difference as modest. By week 52, the gap had about doubled, to 53.6% vs 39.7%.¹ More patients on 15 mg/kg also reached Lupus Low Disease Activity State (37.5% vs 20.5%).¹

Furie compared the week 52 effect size with those of approved agents. He noted that the difference was just under 10 percentage points for belimumab in BLISS-76 and about 15 to 16 percentage points for anifrolumab. The 5 mg/kg dose produced weaker results.

Larger Treatment Effects in Autoantibody-High SLE Subgroups

Furie called the subgroup analyses the most provocative data. Patients who were autoantibody positive made up about 80% of the cohort. To qualify, they needed anti-dsDNA antibodies or another autoantibody beyond ANA. Their SRI-4 response at week 52 was 58.2% with nipocalimab 15 mg/kg vs 36.1% with placebo.¹

A smaller autoantibody-high group, about 15% of the cohort, was identified with a machine learning algorithm. These patients had features such as elevated circulating immune complexes, anti-dsDNA antibodies, and low complement. An interferon-high group made up about two-thirds of the cohort and had a treatment effect in the 20% range.

“For the autoantibody high, it was about 67%, and we never see 67%,” Furie said. “But you have to remember, it’s a very small subgroup.”

Whether the phase 3 GARDENIA trial should focus on one of these subgroups is still an open question.²

IgG Reduction and Infection Risk With Nipocalimab

Nipocalimab was well tolerated overall, according to Furie. It lowers IgG without affecting IgM or IgA. About a quarter of patients reached an IgG nadir near 300 mg/dL, a range he said draws clinical concern depending on background therapy and other isotypes.

In a poster Furie presented at the meeting, patients with IgG levels <200 or <300 mg/dL did not have higher infection rates than patients with levels of 400 to 600 mg/dL. There were 2 deaths, 1 in each nipocalimab group. Furie described both patients as severely ill, possibly before they entered the study, and said more details will appear in the manuscript.

FcRn Blockade vs Cell-Depleting Therapies in Autoimmune Disease

Nipocalimab is approved by the US Food and Drug Administration (FDA) for generalized myasthenia gravis. It is being studied in other IgG-mediated conditions, including Sjögren’s disease and hemolytic disease of the fetus and newborn. Furie contrasted this approach with the CAR T cell therapies and T cell engagers that drew much of the attention at ACR, which aim to eliminate the cells that produce autoantibodies.

“This does not affect the cells themselves. It just shuts off the salvage pathway, and if someone gets into trouble with a low IgG, you stop the drug, and there will be a rebound in probably 2 to 4 weeks,” Furie said.

Editor’s Note: Furie reports relevant disclosures with Johnson & Johnson.

References

1. Johnson & Johnson late-breaking results show nipocalimab significantly reduced systemic lupus erythematosus (SLE) disease activity in a phase 2 study. Johnson & Johnson. Published June 3, 2026.

2. A study of nipocalimab in participants with systemic lupus erythematosus (GARDENIA). ClinicalTrials.gov identifier: NCT07438496.