Nipocalimab Demonstrates Proof of Concept for FcRn Blockade for SLE

Nipocalimab, the first neonatal Fc receptor (FcRn) blocker investigated in systemic lupus erythematosus (SLE), met its primary endpoint and demonstrated sustained reductions in disease activity through 52 weeks in adults with moderate-to-severe SLE, according to late-breaking phase 2 results from the JASMINE-SLE study presented at the European Alliance of Associations for Rheumatology (EULAR), held June 3-6 in London, United Kingdom.^1,2

RheumatologyLive spoke with Richard A. Furie, MD, Marilyn and Barry Rubenstein Chair in Rheumatology, 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, Great Neck, New York, investigator on the study. JASMINE-SLE (NCT04882878) was a randomized, double-blind, placebo-controlled phase 2 study enrolling 228 adults aged 18 to 65 years with moderate-to-severe SLE (SLEDAI-2K ≥6; ≥1 BILAG A or ≥2 BILAG B domain scores), positive ANA, anti-dsDNA, and/or anti-Smith antibodies, and prior inadequate response to ≥1 standard-of-care treatment. Participants were randomized 1:1:1 to intravenous nipocalimab 5 mg/kg, nipocalimab 15 mg/kg, or placebo every 2 weeks through week 52, in addition to protocol-permitted background medications. Baseline characteristics were balanced between arms.¹

The primary endpoint — SRI-4 composite response at week 24 — was achieved by 53.5% of participants receiving nipocalimab 15 mg/kg versus 46.7% receiving placebo (Δ6.8; OR: 1.6 [90% CI, 0.9–2.9]; P = .081), which met the prespecified significance threshold of a 2-sided α = 0.10 appropriate for this phase 2a study. The 5 mg/kg dose did not meet the primary endpoint.1 At week 52, a key secondary endpoint, SRI-4 response was achieved by 53.6% of nipocalimab 15 mg/kg participants versus 39.7% of placebo participants (Δ13.9; nominal P = .020). Lupus Low Disease Activity State (LLDAS), a key exploratory endpoint, was achieved by 37.5% versus 20.5% (Δ17.0; nominal P = .013).¹

Efficacy was more pronounced in prespecified biomarker-enriched subgroups. In the autoantibody-positive population — defined by positive anti-dsDNA, anti-Smith, or ANA with anti-Ro, anti-RNP, or history of anti-dsDNA, representing approximately 80% of people with SLE2 — week 52 SRI-4 response rates were 58.2% versus 36.1% (Δ22.1; nominal P = .004) and LLDAS rates were 38.9% versus 18.0% (Δ20.9; nominal P = .012) for nipocalimab 15 mg/kg versus placebo.1 In the autoantibody-high subgroup — a subset characterized by elevated circulating immune complexes (CICs), high interferon signature, and reduced C3 — week 52 SRI-4 response was 75.8% versus 11.1% (Δ64.7) and LLDAS was 53.5% versus 11.1% (Δ42.4).1 Among IFN-high participants, week 52 SRI-4 response was 57.1% versus 33.3% (Δ23.8; nominal P = .005) and LLDAS 41.5% versus 16.7% (Δ24.8; nominal P = .005).¹

Dose-dependent reductions in total IgG, CICs, and anti-dsDNA were observed through week 52, consistent with the drug's mechanism of FcRn blockade. In participants with low baseline C3, increases in C3 were observed from weeks 32 to 52 in the nipocalimab 15 mg/kg group.1 Through week 58, adverse events (AEs) occurred in 76.0%, 89.6%, and 82.9% of participants receiving placebo, nipocalimab 5 mg/kg, and nipocalimab 15 mg/kg, respectively; infections and infestations were the most common AE category (56.0%, 58.4%, and 60.5%). Serious AEs occurred in 8.0%, 7.8%, and 13.2%, respectively, with serious infections in 3 (4.0%), 4 (5.2%), and 3 (3.9%) participants. Nadir IgG <3 g/L was observed in 22.7% of nipocalimab 15 mg/kg participants; none of these participants developed serious AEs through week 58.1 No new safety signals were identified.²

"The result was positive, especially in subgroups that were enriched for autoantibodies," Furie said. "It's a very interesting concept, and it's been positive in other diseases like myasthenia gravis — we just need to move on from phase 2 to phase 3."

Furie also noted a potential advantage of FcRn blockade over B cell–depleting strategies: the ability to reduce RNA-associated autoantibodies such as anti-SSA, anti-SSB, anti-Smith, and anti-RNP, which are not consistently addressed by anti-CD20 or anti-CD19 agents, with potential implications for conditions including neonatal lupus syndrome and Sjögren syndrome. Nipocalimab received FDA Fast Track designation in SLE in January 2026; the phase 3 GARDENIA study (NCT07438496) is currently recruiting.²

Furie’s disclosures include GSK.

References

1. Furie RA, van Vollenhoven RF, Wojciechowski R, et al. Nipocalimab in SLE: first-in-class efficacy and safety results demonstrating proof of concept for FcRn blockade from the phase 2 JASMINE-SLE study [abstract LB0007]. Ann Rheum Dis. 2026. doi:10.1136/annrheumdis-2026-eular.LBA_B.62

2. Johnson & Johnson. Johnson & Johnson late-breaking results show nipocalimab significantly reduced systemic lupus erythematosus (SLE) disease activity in a phase 2 study [press release]. June 3, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-late-breaking-results-show-nipocalimab-significantly-reduced-systemic-lupus-erythematosus-sle-disease-activity-in-a-phase-2-study