Abstract: SA-OR047
Zanubrutinib in Phospholipase A2 Receptor (PLA2R)-Associated Primary Membranous Nephropathy (PMN): Updated Results of a Phase 2/3, Multicenter, Randomized, Open-Label Study
Session Information
- Glomerular Diseases: Clinical Trial Results
October 24, 2026 | Location: Mile High Ballroom 4A, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Lafayette, Richard A., Stanford University Medical Center, Stanford, California, United States
- Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
- Chen, Yanyan, BeOne Medicines, Ltd, Shanghai, China
- Yao, Zhen, BeOne Medicines, Ltd, Shanghai, China
- Song, Jingwen, BeOne Medicines, Ltd, Shanghai, China
- Li, Guisen, Sichuan Provincial People’s Hospital, Chengdu, China
- Zhao, Minghui, Peking University First Hospital, Beijing, China
Background
Bruton tyrosine kinase (BTK) plays a role in B-cell modulation and is a potential target in PMN. Zanubrutinib (BTK inhibitor) is being evaluated in a 2-part study in PMN (NCT05707377). Part 1 single-arm data are shown.
Methods
After a 12-wk run-in, patients (pts) with PLA2R antibody (Ab) >50 RU/mL and urine protein-creatinine ratio (UPCR) >3.5 mg/mg received zanubrutinib 160 mg BID for 64 wks, followed by 40-wk observation. Endpoints include change from baseline in UPCR, clinical remission, immunologic response, relapse rate, and safety.
Results
As of March 10, 2026, 30 pts were treated; patient demographics and characteristics are shown in Table 1. At 104 wks, mean UPCR change from baseline was −6.0 mg/mg (SD, 2.4), an 83.2% reduction overall. Nine pts (30.0%) had complete remission (UPCR ≤0.3 mg/mg and stable eGFR) and 7 (23.3%) had partial remission (UPCR of >0.3 to ≤3.5 mg/mg, with a ≥50% decrease from baseline, and stable eGFR), resulting in an overall remission rate of 53.3%. Kaplan-Meier estimated median time to first overall remission was 51.6 wks (Fig 1). Immunologic response rate (anti-PLA2R titer reduction to <14 RU/mL) was 50.0%, and relapse rate was 0%. 28 pts (93.3%) had treatment (tx)-emergent adverse events (TEAEs); most common (≥20%) TEAEs were upper respiratory tract infection (30.0%), anemia (26.7%), rash (23.3%), hypocalcemia (20%), and hypokalemia (20%). Four pts (13.3%) had severe TEAEs (pneumonia and increased blood creatine phosphokinase were tx-related [n=1 each]).
Conclusion
In primary PMN, zanubrutinib is generally well tolerated, and 64-wk tx led to immunologic and clinical remission in just over 50% of pts, which was sustained during the 40-week follow-up. These results support continued evaluation of zanubrutinib in PMN.
Funding
- Commercial Support – BeOne Medicines, Ltd.