Treatment for Primary Membranous Nephropathy: Feasibility Study Results

Researchers have identified Bruton tyrosine kinase (BTK) as playing an important role in modulation of B cells, providing a potential therapeutic target for the treatment of primary membranous nephropathy (PMN), an antibody-driven glomerular disease.

During a poster session at ASN Kidney Week 2024, Richard A. Lafayette, MD, and colleagues presented results of a phase 2/3 study examining the efficacy and safety of zanubrutinib in patients with PMN. The poster was titled Zanubrutinib for the Treatment of Primary Membranous Nephropathy (PMN): Results of a Single-Arm Feasibility Study.

Zanubrutinib is a highly selective inhibitor of BTK. The two-part, open-label study included 30 patients. Eligible patients had anti-phospholipase A2 receptor (PLA2R) antibody ≥50 RU/mL and urinary protein-creatinine ratio (UPCR) >3.5 g/g. Following a 12-week run-in period that included optimal supportive care, participants received zanubrutinib 160 mg twice a day for 64 weeks. The treatment phase was followed by a 40-week observation period.

The primary endpoint of interest was the change in UPCR from baseline at week 24. Secondary outcomes included anti-PLA2R antibody titer, serum albumin level, overall remission rate, and safety.

Of the 30 participants, 66.7% were men and 93.3% were Asian. Baseline values were median UPCR 7.5 g/g, serum albumin 23.5 g/L, and eGFR 85.2 mL/min/1.73 m². Median duration of exposure as of July 15, 2024, was 26.5 weeks, and 20 patients had completed the week 24 visit (five patients discontinued early).

Median change from baseline in UPCR at 24 weeks was –1.5 g/g. Six patients (30%) had partial remission, defined as UPCR 0.3-3.5 g/g and ≥50% decrease from baseline, and stable eGFR. The immunological response rate, defined as anti-PLA2R titer reduction to <14 RU/mL, was 60%.

In safety measures, 87% of patients (n=26) had treatment-emergent adverse events, primarily upper respiratory tract infections (27%), rash (20%), and hypokalemia (17%). Four participants had severe treatment-emergent adverse reactions. One of those was treatment-related.

In summary, the authors said, “Zanubrutinib appears to be generally well tolerated and shows activity in patients with PMN.”

Source: Lafayette RA, Barbour S, Chen Y, et al. Zanubrutinib for the treatment of primary membranous nephropathy (PMN): results of a single-arm feasibility study. TH-PO1204. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2024; October 24, 2024; San Diego, California. Funding for the study was provided by Bei-Gene Co., Ltd.