The analysis of circulating immune cell subsets demonstrated that Ianalumab significantly reduced CD19+ B cell counts by Week 28, eliminating detectable B cell subsets such as transitional, naïve, and memory B cells, as well as plasmablasts/plasma cells. Whole blood transcriptome analysis corroborated these findings, showing a marked reduction in B cell subsets at Week 28, consistent with flow cytometry results.

Additionally, autoantibody titers, including anti-dsDNA, anti-C1q, and anti-ENAs, decreased from Week 12 to Week 68 in patients treated with Ianalumab compared to placebo. U1RNP kinetics illustrated consistent reductions across various autoantibodies in the Theradiag panel for Ianalumab-treated patients. Moreover, patients who achieved a composite of SRI-4 response and corticosteroid responder status by Week 28 showed normalized reductions in neutrophil counts and a decrease in the interferon gene signature (IFNGS) over time, compared to non-responders, underscoring Ianalumab's potential in treating SLE.

Conclusion

Novartis' ianalumab, an investigational monoclonal antibody targeting BAFF, shows promising potential in treating lupus. Ianalumab, currently in development for various autoimmune conditions including autoimmune hepatitis, primary Sjogren’s syndrome, SLE, rheumatoid arthritis, and several types of B-cell non-Hodgkin lymphomas. By inhibiting BAFF, ianalumab aims to reduce inflammation and immune activity, thus alleviating lupus symptoms. Phase II trials indicate favorable tolerability, effective B cell depletion, and achievement of primary endpoints with additional beneficial outcomes. These positive results justify the progression to Phase III trials (SIRIUS-SLE 1 and SIRIUS-SLE 2), with a planned filing expected in 2027 or later. The ongoing trials will be critical in determining ianalumab's efficacy and safety profile, potentially positioning it as a significant advancement in lupus treatment.

In 2023, BENLYSTA dominated the current market of SLE. A few emerging therapies in the pipeline, including cenerimod, ianalumab, and deucravacitinib, are expected to bring a positive shift in the SLE treatment landscape. Ianalumab is expected to capture ~USD 600 million by 2034 in the US.

Ianalumab demonstrated significant B cell depletion in SLE patients, validated by both flow cytometry and transcriptomic analyses, alongside a marked decrease in autoantibodies. Early findings suggest that reductions in B cells and autoantibodies correlated with normalized neutrophil counts and reduced IFNGS levels specifically in composite SRI-4 responders by Week 28. Ongoing biomarker studies aim to further elucidate Ianalumab's impact on these patients, highlighting its potential as a promising therapeutic option for SLE.