Abstract: FR-OR033
Whole-Blood RNA Sequencing (RNAseq) Profiling Identifies Functionally Enriched Gene Expression Patterns in Felzartamab-Treated Patients with IgAN: Data from the Phase 2 IGNAZ Study
Session Information
- Glomerular Disease Outcomes: Measuring What Matters
November 07, 2025 | Location: Room 310A, Convention Center
Abstract Time: 05:20 PM - 05:30 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Shah, Millie, Biogen, South San Francisco, California, United States
- Chen, Yirui, Biogen, South San Francisco, California, United States
- Delfino, Tess Arenzana, Biogen, South San Francisco, California, United States
- Kivman, Lisa, Biogen, South San Francisco, California, United States
- Kräft, Tabea, MorphoSys GmbH, a Novartis company, Planegg, Bavaria, Germany
- Chinn, Leslie, Biogen, South San Francisco, California, United States
- Schwartz, Brian, Biogen, South San Francisco, California, United States
- Jones, Nicholas S, Biogen, South San Francisco, California, United States
- Beckett, Valeria, Biogen, South San Francisco, California, United States
- Patel, Uptal D., Biogen, South San Francisco, California, United States
- Flesher, Donna, Biogen, South San Francisco, California, United States
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
- Kiryluk, Krzysztof, Columbia University, New York, New York, United States
Background
Felzartamab, a fully human anti-CD38 monoclonal antibody targeting CD38+ plasmablasts and plasma cells, reduced proteinuria and stabilized eGFR in patients with IgA nephropathy (IgAN) in the Phase 2 IGNAZ study (NCT05065970). We used whole blood RNAseq profiling to examine gene expression patterns in felzartamab-treated patients with IgAN.
Methods
In Part 1 of IGNAZ, 48 patients with IgAN were randomized 1:1:1:1 to placebo or intravenous felzartamab (2, 5, or 9 doses). In Part 2, 6 Japanese patients received the open-label 9-dose regimen. Whole blood was collected in PAXgene® Blood RNA Tubes over time and bulk RNA sequencing was performed (Illumina NovaSeq X). Differential expression, gene clustering, functional enrichment, gene set variation, and cellular deconvolution analyses were performed to identify changes following felzartamab treatment.
Results
Overall, 792 genes were differentially expressed in felzartamab-treated patients (9-dose arms) compared to placebo. Two significantly downregulated genes, JCHAIN and IGHA1, have been previously identified as part of a plasma cell gene signature and are relevant to the pathogenesis of IgAN. Differentially expressed genes clustered into distinct groups displaying treatment-associated reductions over time. Gene clusters were functionally enriched for gene programs related to CD38+ cellular subsets. Treatment-associated reduction in these clusters were consistent with the mechanism of action of felzartamab and corresponding clinical observations of circulating immunoglobulins, B lineage subsets, and lymphocyte subsets. Additionally, cluster gene set variation analysis showed dose regimen–dependent trends over time.
Conclusion
Felzartamab treatment-related gene expression changes detected by whole blood RNAseq are functionally enriched for CD38+ cell types, including immunoglobulin and IgA-related genes, supporting targeting and reduction of plasma cells in IgAN. These results validate the use of this dataset for further analyses to understand the mechanism of action of felzartamab and to further characterize felzartamab treatment response in patients with IgAN.
Funding
- Commercial Support – This study was sponsored by HI-Bio, Inc, a Biogen company, and MorphoSys GmbH, a Novartis company.