Zanubrutinib for the Treatment of Primary Membranous Nephropathy (PMN): Results of a Single-Arm Feasibility Study
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.003 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".