A Phase 2 trial has revealed promising results for felzartamab, an investigational anti-CD38 monoclonal antibody, in reducing proteinuria and maintaining kidney function in patients with IgA nephropathy (IgAN). The findings, presented at ASN Kidney Week 2024, highlight the potential of felzartamab to address the underlying molecular mechanisms driving IgAN. IgAN is an autoimmune kidney disease characterized by the deposition of immune complexes in the kidneys, leading to inflammation and loss of kidney function.
It is hypothesized that CD38+ cells contribute to disease through the secretion of galactose-deficient IgA1 (Gd-IgA1) as well as anti-Gd-IgA1 antibodies, which subsequently form immune complexes that deposit in the kidneys and cause inflammation and downstream loss of kidney function.
Felzartamab's Impact on Immune Markers
Researchers analyzed whole-blood and serum samples from IgAN patients before, during, and after felzartamab treatment to evaluate its effects on immune cells, antibodies, and immunoglobulins, including Gd-IgA1. The analyses demonstrated that felzartamab induced a rapid and durable depletion of Gd-IgA1 and total IgA antibodies. Patients who received nine doses over a six-month treatment period maintained Gd-IgA1 reduction for up to nine months off-treatment. Total IgA reduction was sustained for at least 18 months off-treatment. In contrast, total IgG antibody titers were modestly reduced and recovered within four months off-treatment, suggesting the preservation of components of the body's adaptive immune response.
Expert Commentary
"These data further our understanding of the role of CD38+ antibody secreting cells in IgA nephropathy pathogenesis," said Millie Shah, PhD, Senior Scientist at Biogen and corresponding author of the study. "By directly depleting these cells, felzartamab reduces the cellular drivers of disease and has the potential for durable clinical benefit without continuous dosing, potentially lowering patient burden and offering improved tolerability."
The study, titled "Felzartamab durably reduces disease relevant biomarkers through targeting of CD38+ plasma cells and plasmablasts, the upstream drivers of IgA nephropathy (IgAN)," provides insights into the potential of felzartamab as a targeted therapy for IgAN.
