TOPLINE:
Iscalimab, a novel anti-CD40 monoclonal antibody, showed efficacy in lupus nephritis (LN) by reducing proteinuria at 24 weeks compared with placebo. The treatment was generally well tolerated, with most adverse events being mild to moderate.
METHODOLOGY:
- Researchers conducted a phase 2 randomized study to evaluate the efficacy, pharmacokinetics, and safety of iscalimab vs placebo as an add-on to standard-of-care therapy in patients with biopsy-proven active proliferative LN.
- Overall, 57 patients with proliferative LN class III or IV who met four or more American College of Rheumatology criteria for systemic lupus erythematosus with a urinary protein-to-creatinine ratio of ≥ 0.5 mg/mg (56.52 mg/mmol) and sufficient kidney function were included.
- Patients were randomly assigned to receive either seven intravenous infusions of 10 mg/kg iscalimab (n = 39; median age, 33 years; 76.9% women) or placebo (n = 18; median age, 34.5 years; 94.4% women) as an add-on to standard-of-care therapy for LN during the 24-week treatment period.
- Standard-of-care therapy included stable doses of corticosteroids, mycophenolate, azathioprine, methotrexate, and antimalarials.
- The primary endpoint was the effect of iscalimab vs placebo on renal proteinuria, measured using the urinary protein-to-creatinine ratio, at week 24. Adverse events and serious adverse events were assessed during treatment and over a 24-week follow-up period.
TAKEAWAY:
- At week 24, iscalimab led to a statistically significant reduction of 42.1% (predefined criterion of > 20%) in the urinary protein-to-creatinine ratio compared with placebo, with relative improvements of 63.1% and 36.3% from baseline in the iscalimab and placebo arms, respectively.
- The proportion of patients achieving complete renal remission was 8.1% in the iscalimab group compared with 0% in the placebo group.
- At week 24, a greater reduction in the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index was observed with iscalimab than with placebo (a decrease of 2.8 vs 1.1 points).
- The incidence of adverse events was high in both groups, with most of them being mild to moderate. Four adverse events led to treatment discontinuation (three in the iscalimab group and one in the placebo group).
IN PRACTICE:
“The results have shown that iscalimab was clinically effective and generally well tolerated, despite some severe infections in comorbid patients on multiple concomitant immunosuppressive therapies,” the authors wrote.
SOURCE:
The study was led by Nan Shen, MD, PhD, Shanghai JiaoTong University School of Medicine in Shanghai, China. It was published online on August 14, 2025, in RMD Open.
LIMITATIONS:
The sample size was small, and the duration of the trial was short. The high discontinuation rate, which was similar in the two groups (46.2% in the iscalimab group and 44.4% in the placebo group), could have introduced bias. The study did not have enough power to show statistically significant changes in secondary and exploratory outcomes.
DISCLOSURES:
The study was funded by Novartis Pharma AG in Basel, Switzerland. Seven authors are employees of Novartis, and one author was employed by the company at the time of the study. Some authors reported receiving consulting fees, payment or honoraria, and other financial support from pharmaceutical companies including GSK, AstraZeneca, Roche, Bristol Myers Squibb, or Pfizer.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.