LONDON — The anti-Fc receptor (FcRn) antibody nipocalimab significantly improved systemic lupus erythematosus (SLE) disease activity measures to a greater extent than did placebo in a phase 2b study reported at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting.

In the JASMINE-SLE study, treatment with nipocalimab 15 mg/kg led to a higher percentage of participants meeting the primary endpoint of an SLE Responder Index (SRI)-4 composite response at week 24 than with placebo, at 53.5% vs 46.7% (P = .081).

Moreover, results at 1 year showed that the effect size was doubled from 6.8% to 13.9% in favor of nipocalimab 15 mg/kg vs placebo (53.6% vs 39.7%; P = .020).

Results with the lower 5 mg/kg dose that was used in the trial were also higher than with placebo at 24 weeks and 1 year, but the differences were not statistically significant.

Greater treatment effects were seen in subpopulations of patients who were autoantibody positive, had high autoantibody levels, or high levels of interferon (IFN).

‘Proof-of-Concept’ Study in SLE

This was a “proof-of-concept study,” and supported nipocalimab’s further development in SLE, said the presenting study investigator Richard Furie, MD, chief of rheumatology at Feinstein Institutes for Medical Research, Northwell Health in Manhasset, New York.

These were important data on extrapolation of FcRn-blockade to other rheumatic and musculoskeletal diseases, Md Yuzaiful Md Yusof, MB ChB, PhD, who was not involved in the study, told Medscape Medical News.

Nipocalimab has already been approved as a treatment for generalized myasthenia gravis and has shown efficacy in Sjögren disease, although it missed its mark in rheumatoid arthritis.

Md Yusof, who is an associate professor and honorary consultant rheumatologist within the Leeds Institute of Rheumatic and Musculoskeletal Medicine in Leeds, England, observed that the placebo response of 46.7% was high, but that was “similar to most of the other SLE trials.”

The high placebo response rates seen in the trial could have been because concomitant glucocorticoid use was allowed, Md Yusof suggested. The trial had a mandated tapering strategy to try to get the glucocorticoid dose to a target 7.5 mg/d from weeks 6 to 16, but thereafter it was done according to the investigator’s discretion.

Study Design

The JASMINE-SLE study design was “much like all of our SLE trials,” Furie reported. “In order to be eligible, patients had to have a SLEDAI [SLE Disease Activity Index] of 6 or greater, a BILAG [British Isles Lupus Assessment Group] A or two [BILAG] B’s, and to be serologically active.”

A total of 221 participants were recruited and randomly allocated to one of the three study arms: 77 were treated with nipocalimab 5 mg/kg, 76 with nipocalimab 15 mg/kg, and 75 were given a matching placebo. Treatment was given intravenously every 2 weeks.

Overall, the mean age of the study participants was 43.4 years, almost all (94.6%) were women, and nearly two thirds (65.2%) were White. The average duration of SLE was 9.4 years, and the baseline SLEDAI-2K score was 10.1.

About half the study population was taking immunomodulatory drugs, 71% oral glucocorticoids, and 85% antimalarials.

Best Results When Autoantibody Levels Are High

Efficacy of nipocalimab was assessed in three predefined subpopulations of patients.

The largest group (79% of participants) included those who were found to have at least one positive result for an autoantibody, such as anti-double stranded (ds) DNA, anti-Smith, antinuclear antibody with anti-ribonucleoprotein, anti-Ro, or historic anti-dsDNA, among others.

The next largest group (66%) had high levels of IFN, which was defined using a peripheral blood RNA signature.

Finally, the smallest group (15%) was a subset of the autoantibody-positive group who had high levels of autoantibodies, increased circulating immune complexes, a high IFN signature, and low complement C3.

The mean difference between the nipocalimab 15 mg/kg group and placebo in the SRI-4 Composite Response at 52 weeks was 22.1% in the autoantibody-positive group, 23.8% in the IFN-high group, but 64.7% in the autoantibody high group.

Nipocalimab Safety Data on Par With Previous Studies

Adverse events were recorded in 89.6% and 82.9% of participants on nipocalimab 5 mg/kg and nipocalimab15 mg/kg, respectively, and in 76.0% of the placebo group.

Serious adverse event rates were a respective 7.8%, 13.2%, and 8.0%.

There were three cases of sepsis, “one in each treatment arm,” Furie said. “Two out of the three died, and they happened to be in the nipocalimab arms.” However, the deaths were not thought to be related to the study medication.

Infection rates were similar across the three groups, at a respective 60.5%, 58.4%, and 56.0%.

Md Yusof pointed out that 23% of the patients in the 15 mg/kg group had low (< 3 g/L) levels of immunoglobulin (Ig)G.

“Although, these patients did not have an infection, longer-term safety data are needed, as well as seeing if the IgG level will recover,” he said. Md Yusof also noted that vaccination response data in these people were required and if they may need Ig replacement therapy.

Take-Home Thoughts

Overall, said Md Yusof, “nipocalimab provides a different mode of action to currently approved biologics. Patients with nonrenal SLE, with multiple autoantibodies beyond anti-dsDNA, low complement, and high IgG may suit this therapy well.”

Although important questions remained, such as the duration of nipocalimab treatment, he looked forward to seeing the results of the phase 3 GARDENIA study that will follow, as well as long long-term safety data from extension studies.

The study was funded by Johnson & Johnson. Furie reported receiving grant funding from Genentech/Roche, and personal fees from AstraZeneca, Biogen, Bristol Myers Squibb, GlaxoSmithKline, and Johnson & Johnson.

Md Yusof reported receiving consulting fees from Aurinia Pharmaceuticals, UCB, and Autolus; advisory board participation for GlaxoSmithKline and Novartis; and receiving speaker fees from Alumis, CSL Vifor, Grifols, Novartis, Roche, and UCB.

Sara Freeman, MSc, is a freelance medical journalist based in London, England. She has been reporting for specialist healthcare news organizations for more than 20 years.