IgA Nephropathy: An Autoimmune Disease Sees Potential Benefit in Felzartamab Antibody

The autoimmune kidney disease known as IgA nephropathy or Immunoglobulin A nephropathy (IgAN) is caused by immune cells that have the protein CD38 on their surface. An experimental anti-CD38 monoclonal antibody called felzartamab has demonstrated its efficacy in aiding patients to preserve kidney function and minimize proteinuria. This study was conducted recently as a Phase 2 clinical trial. The molecular processes behind felzartamab's possible effectiveness in IgAN were assessed by researchers. The results will be discussed during October 23–27, 2024, ASN Kidney Week (1^✔ ✔Trusted Source
A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection

Go to source). ASN is the American Society of Nephrology. It has been at the forefront of efforts since 1966 to prevent, treat, and cure kidney diseases globally. This is achieved through the education of healthcare professionals and researchers, the promotion of research and innovation, sharing new knowledge, and encouraging the highest standards of patient care.

Antibodies Create Complexes Leading to Impaired Kidney Function

Scientists have postulated that CD38+ cells have a role in this kidney disease by secreting anti-Gd-IgA1 and galactose-deficient IgA1 (Gd-IgA1) antibodies. These antibodies then combine to create immune complexes that accumulate in the kidneys, causing inflammation and ultimately impaired kidney function.

In the study, the researchers analyzed whole blood and serum from IgAN patients at three stages: before, during, and after treatment with felzartamab. The samples were evaluated for immune cells, antibodies, and immunoglobulins, including Gd-IgA1.

How Felzartamab Benefits Nephropathy Patients

The analyses demonstrated that felzartamab led to a sharp and sustained reduction of Gd-IgA1 and total IgA antibodies. Patients who were administered 9 doses during a 6-month treatment regimen experienced a continued decrease in Gd-IgA1 levels for as long as 9 months, even after discontinuation of treatment. Furthermore, the reduction in total IgA was sustained for a minimum of 18 months post-treatment. In contrast, the overall levels of IgG antibodies in the body showed a modest decline, with recovery occurring within 4 months of treatment, indicating that certain elements of the body's adaptive immune response were preserved.

“These data further our understanding of the role of CD38+ antibody-secreting cells in IgA nephropathy pathogenesis,” said corresponding author Millie Shah, PhD, Senior Scientist at Biogen. “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.”

Reference:

1. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection - (https://www.nejm.org/doi/full/10.1056/NEJMoa2400763)

Source-Eurekalert