Kidney Week

Abstract: TH-PO1204

Zanubrutinib for the Treatment of Primary Membranous Nephropathy (PMN): Results of a Single-Arm Feasibility Study

Session Information

• Late-Breaking Science Posters
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Lafayette, Richard A., Stanford University Medical Center, Stanford, California, United States

Richard A. Lafayette, MD

• Barbour, Sean, University of British Columbia, Vancouver, British Columbia, Canada

Sean Barbour, MD, MS, MSc

• Chen, Yanyan, BeiGene Co., Ltd, Shanghai, China

Yanyan Chen, MD

• Yao, Zhen, BeiGene Co., Ltd, Shanghai, China

Zhen Yao

• Chen, Shengnan, BeiGene Co., Ltd, Shanghai, China

Shengnan Chen, PhD

• Li, Guisen, Sichuan Provincial People’s Hospital, Chengdu, China

Guisen Li, MD, PhD

• Zhao, Ming-Hui, Peking University First Hospital, Beijing, Beijing, China

Ming-Hui Zhao, MD, PhD

Background

Bruton tyrosine kinase (BTK) plays a key role in B cell modulation and is a potential therapeutic target in PMN, an antibody-driven glomerular disease. The efficacy and safety of zanubrutinib, a highly selective inhibitor of BTK, is being evaluated in a 2-part, phase 2/3 open-label study in patients (pts) with PMN. Here, part 1 is presented.

Methods

After a 12-wk run-in with optimal supportive care, pts with anti-phospholipase A2 receptor (PLA2R) antibody (Ab) >50 RU/mL and urinary protein-creatinine ratio (UPCR) >3.5 g/g receive zanubrutinib 160 mg BID for 64 wks, followed by a 40-wk observation period. Primary endpoint: change from baseline in UPCR at wk 24; secondary endpoints: anti-PLA2R Ab titer, serum albumin, overall remission rate, safety.

Results

Of 30 pts, most were men (66.7%) and Asian (93.3%). At baseline, median (range) UPCR was 7.5 g/g (3.6, 14.8), serum anti-PLA2R Ab was 161.0 (51.4, 1219.8) RU/mL, serum albumin was 23.5 (15.4, 42.3) g/L, and eGFR was 85.2 (39.8, 123.0) mL/min/1.73m². As of July 15, 2024, the median duration of exposure was 26.5 wks, and 20 pts had completed the wk 24 visit (5 pts discontinued early). At 24 wks, median change from baseline in UPCR was -1.5 g/g (-8.8, 5.7); 6 pts (30%) had partial remission (UPCR 0.3–3.5 g/g and ≥50% decrease from baseline, stable eGFR), and the immunological response rate (anti-PLA2R titer reduction to <14 RU/mL) was 60% (Figure). Overall, 26 pts (87%) had treatment-emergent adverse events (TEAEs), mostly (≥15% pts) upper respiratory tract infections (27%), rash (20%), and hypokalemia (17%). 4 pts (13%) had severe TEAEs (treatment-related in 1 pt).

Conclusion

Zanubrutinib appears to be generally well tolerated and shows activity in pts with PMN.

Funding

• Commercial Support – BeiGene Co., Ltd.