FELZARTAMAB REDUCES APLA2R AB BY SELECTIVELY DEPLETING CD38+ PLASMA CELLS AND PLASMABLASTS, THE MAIN PATHOGENIC CELLULAR DRIVERS OF DISEASE IN PRIMARY MEMBRANOUS NEPHROPATHY (PMN)

Introduction:

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 6mo was observed across both M-PLACE (9 infusions) and NewPLACE (5 or 2 infusions). Depletion of detectable CD38+ plasmablast cell counts 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).

Conclusions:

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. 

This abstract was also submitted for ASN Kidney Week 2023 congress. 

Table 1. Median baseline values and % change in key biomarkers in M-Place and NewPlace trials 

I have potential conflict of interest to disclose.
Human Immunology Biosciences, Inc, a Biogen Company

I did not use generative AI and AI-assisted technologies in the writing process.