Abstract: SA-PO910
Felzartamab Reduces aPLA2R Ab by Selectively Depleting CD38+ Plasma Cells and Plasmablasts, the Main Pathogenic Cellular Drivers of Disease in Primary Membranous Nephropathy (PMN)
Session Information
- Glomerular Diseases: Therapeutics
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Flesher, Donna, Human Immunology Biosciences Inc, South San Francisco, California, United States
- Boxhammer, Rainer, MorphoSys AG, Planegg, Germany
- Kräft, Tabea, MorphoSys AG, Planegg, Germany
- Kivman, Lisa, Human Immunology Biosciences Inc, South San Francisco, California, United States
- Haertle, Stefan, MorphoSys AG, Planegg, Germany
- Dudani, Jaideep, Human Immunology Biosciences Inc, South San Francisco, California, United States
- Gilbert, Houston N., Human Immunology Biosciences Inc, South San Francisco, California, United States
- Patel, Uptal D., Human Immunology Biosciences Inc, South San Francisco, California, United States
- Rovin, Brad H., The Ohio State University, Columbus, Ohio, United States
Background
Felzartamab (felza) is a fully human monoclonal antibody that binds to CD38 with high affinity and depletes CD38+ antibody-producing cells such as plasma cells/plasmablasts primarily via antibody-dependent cellular cytotoxicity & phagocytosis. In studies of high-risk PMN patients, felza substantially reduced aPLA2R with associated improvements in UPCR and serum albumin. To further characterize felza with respect to efficacy biomarkers and preservation of protective immunity, we analyzed samples collected prospectively during the M-PLACE (NCT04145440) and NewPLACE (NCT04733040) trials.
Methods
Serum and whole blood were collected pre/post- felza treatment in patients with aPLA2R+ PMN. Biomarker analyses were performed for aPLA2R (ELISA), total IgG (turbidimetry), anti-Tetanus Toxoid (TT) (ELISA), and B cell populations (flow cytometry).
Results
Felza reduced aPLA2R comparably in patients with baseline levels <150 and >150 RU/mL (Table 1). A dose-dependent effect on aPLA2R reduction at 6 months was observed across both M-PLACE (9 infusions) and NewPLACE (5 or 2 infusions). Depletion of detectable CD38+ plasmablasts was observed 1 wk after felza treatment. Treatment did not impact other B cell populations, as absolute counts of total, naïve, and memory B cells were unchanged. Total IgG decreased on treatment then recovered above baseline by end of study. Anti-TT titers decreased on treatment, however levels were maintained above the protective threshold (0.1 IU/mL).
Conclusion
Felza selectively depleted CD38+ plasmablasts and plasma cells, reducing pathogenic aPLA2R to a greater extent than protective anti-TT titers and total IgG, which was dose-dependent and durable. Treatment of PMN with Felza suggests an efficient and selective treatment concept with preservation of vaccine response compared to conventional immunosuppressive therapies.
Table 1. Median baseline values and % change in key biomarkers in M-Place and NewPlace trials
Funding
- Commercial Support – Human Immunology Biosciences Inc, MorphoSys AG