RARE DISEASE
Primary membranous glomerulonephritis
Primary membranous glomerulonephritis
Primary membranous glomerulonephritis
Synonyms: Idiopathic membranous glomerulonephritis, Primary membranous nephropathy
Synonyms: Idiopathic membranous glomerulonephritis, Primary membranous nephropathy
Synonyms: Idiopathic membranous glomerulonephritis, Primary membranous nephropathy
Drug discovery
12
drugs
With orphan designations
Overview
Primary Membranous Glomerulonephritis (PMN) is an autoimmune kidney disease characterized by immune complex deposition in glomeruli, primarily targeting podocyte antigens (e.g., PLA2R in 70%, THSD7A in 3-9%). It manifests as nephrotic syndrome or proteinuria, with 30-40% progressing to end-stage kidney disease (ESKD) within 10 years. Diagnosis combines serum anti-PLA2R/THSD7A antibodies and kidney biopsy with immunohistochemistry [1][2][6][10].
Therapies
Categories: rare renal diseases, rare transplant-related disorders
Research Papers
1,371 drug discovery papers related to Primary membranous glomerulonephritis, with 4 first-in-class and 7 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,371 drug discovery papers related to Primary membranous glomerulonephritis, with 4 first-in-class and 7 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-11 | Efficacy and safety of obinutuzumab in patients with primary membranous nephropathy: a focus on refractory and rituximab-resistant patients.
There has been an annual rise in the incidence of primary membranous nephropathy (PMN), a common pathological type of nephrotic syndrome (NS). Obinutuzumab is a humanised, glycosylated, type II anti-CD20 monoclonal antibody. Characterised by its enhanced B-cell depletion capability compared with rituximab (RTX), obinutuzumab has demonstrated promising efficacy in the treatment of membranous nephropathy. This study aimed to investigate the efficacy and safety of obinutuzumab in treating various subtypes of PMN. A total of 94 PMN patients with NS were enrolled in this study. Based on their treatment history before receiving obinutuzumab, the patients were categorised into the Initial therapy group (group A, n=32), the Refractory group (group B, n=32), and the Remedial therapy group (group C, n=30). The efficacy and safety of obinutuzumab treatment after a 24-month follow-up period were observed and analysed in each group. The primary endpoint was the clinical remission rate (complete remission + partial remission) at 24 months, and the secondary endpoints were treatment safety and the incidence of treatment-emergent adverse events. Following 24 months of obinutuzumab therapy, 95.74% (90/94) of the PMN patients achieved clinical remission, with 28.72% (27/94) reaching complete remission (CR) and 67.02% (63/94) achieving partial remission (PR). The Initial therapy group (group A) achieved a 100% (32/32) clinical remission rate: 37.5% (12/32) attained CR, and 62.5% (20/32) attained PR. The Refractory group (group B) achieved a 96.88% (31/32) clinical remission rate: 25% (8/32) attained CR, and 71.88% (23/32) attained PR. The Remedial therapy group (group C) achieved a 90% (27/30) clinical remission rate: 23.33% (7/30) attained CR, and 66.67% (20/30) attained PR. All 63 anti-PLA2R antibody-positive (>20 U/mL) patients and 16 anti-PLA2R antibody negativity but no immunological remission (2-20 U/mL) patients demonstrated declining antibody levels following obinutuzumab therapy, and 68.4% (54/79) attained complete immunological remission (<2 U/mL). Obinutuzumab demonstrates high clinical remission rates and acceptable safety in PMN patients, with good efficacy even in refractory and RTX-resistant patients.
2026-07-11 | Artificial intelligence in membranous nephropathy: transforming clinical management toward precision medicine.
Membranous Nephropathy (MN) is the leading cause of primary nephrotic syndrome in adults, characterized by significant clinical heterogeneity ranging from spontaneous remission to end-stage kidney disease. Current management of membranous nephropathy, which relies heavily on renal biopsy and static serological markers such as anti-PLA2R antibodies, often fails to predict individual disease trajectories. This limitation frequently leads to empirical immunosuppressive therapy with a trial-and-error approach. This review explores the transformative potential of Artificial Intelligence (AI) in reshaping MN management from evidence-based to data-driven and predictive medicine. We examine AI-driven innovations across the clinical spectrum: from computational pathology systems that automate glomerular morphometry with high objectivity and reproducibility, to non-invasive diagnostic models integrating radiomics and serology for non-invasive diagnosis. In therapeutics, we discuss machine learning algorithms that predict individual responses to Rituximab versus Cyclophosphamide, enabling personalized regimen selection. Furthermore, we highlight the role of AI in prognostic stratification, where dynamic in silico patient models and multi-omics integration unravel molecular subtypes and forecast renal survival with high granularity. While acknowledging critical challenges such as data silos, model interpretability gaps, and the need for global validation, we conclude that AI serves as a powerful augmentation tool. By synthesizing high-dimensional data into actionable insights, AI has the potential to facilitate increasingly predictive, preventative, and personalized care strategies in MN management.
2026-07-10 | Real-World Long-term Comparisons of Rituximab versus Calcineurin Inhibitors for Membranous Nephropathy in the Cure Glomerulonephropathy Study.
Clinical trials in rare glomerular disease may establish short-term treatment efficacy but are limited by small sample sizes and short study duration. Observational data are needed to assess longer-term outcomes and can provide insights into real-world prescribing practices. This study applied modern statistical methods to real-world data from the Cure Glomerulonephropathy (CureGN) network to compare the effectiveness of rituximab and calcineurin inhibitors on long-term primary membranous nephropathy outcomes. CureGN participants with biopsy-confirmed primary membranous nephropathy who initiated either of the two treatments at least 6 months after any previous immunosuppressant exposure were eligible. Inverse-probability-of-treatment weighting balanced covariates at treatment initiation. Inverse-probability-of-censoring weights accounted for censoring individuals if another immunosuppressant was started during follow-up. Outcomes included time from treatment initiation to composite kidney disease progression (40% decline in eGFR, kidney replacement therapy, or eGFR <15), proteinuria remission, and relapse following remission. Hazard ratios and differences in restricted mean survival times were estimated. 325 treatment initiations across 250 unique participants were eligible, with median follow-up 53 months (25th-75th percentile: 24-79). Participants on calcineurin inhibitors had significantly higher risks of disease progression (HR=2.81; 95% CI: 1.16, 6.80). Hazard ratios for proteinuria remission (HR=0.77; 95% CI: 0.50, 1.17) and relapse (HR=1.42, 95% CI: 0.69, 2.92) had wide confidence intervals. Rituximab was associated with better kidney function preservation than calcineurin inhibitors over long follow-up. Proteinuria remission and relapse results favored rituximab but did not reach statistical significance. Long-term treatment comparative effectiveness in rare diseases can be evaluated with real-world data.
2026-07-11 | Efficacy and safety of obinutuzumab in patients with primary membranous nephropathy: a focus on refractory and rituximab-resistant patients.
There has been an annual rise in the incidence of primary membranous nephropathy (PMN), a common pathological type of nephrotic syndrome (NS). Obinutuzumab is a humanised, glycosylated, type II anti-CD20 monoclonal antibody. Characterised by its enhanced B-cell depletion capability compared with rituximab (RTX), obinutuzumab has demonstrated promising efficacy in the treatment of membranous nephropathy. This study aimed to investigate the efficacy and safety of obinutuzumab in treating various subtypes of PMN. A total of 94 PMN patients with NS were enrolled in this study. Based on their treatment history before receiving obinutuzumab, the patients were categorised into the Initial therapy group (group A, n=32), the Refractory group (group B, n=32), and the Remedial therapy group (group C, n=30). The efficacy and safety of obinutuzumab treatment after a 24-month follow-up period were observed and analysed in each group. The primary endpoint was the clinical remission rate (complete remission + partial remission) at 24 months, and the secondary endpoints were treatment safety and the incidence of treatment-emergent adverse events. Following 24 months of obinutuzumab therapy, 95.74% (90/94) of the PMN patients achieved clinical remission, with 28.72% (27/94) reaching complete remission (CR) and 67.02% (63/94) achieving partial remission (PR). The Initial therapy group (group A) achieved a 100% (32/32) clinical remission rate: 37.5% (12/32) attained CR, and 62.5% (20/32) attained PR. The Refractory group (group B) achieved a 96.88% (31/32) clinical remission rate: 25% (8/32) attained CR, and 71.88% (23/32) attained PR. The Remedial therapy group (group C) achieved a 90% (27/30) clinical remission rate: 23.33% (7/30) attained CR, and 66.67% (20/30) attained PR. All 63 anti-PLA2R antibody-positive (>20 U/mL) patients and 16 anti-PLA2R antibody negativity but no immunological remission (2-20 U/mL) patients demonstrated declining antibody levels following obinutuzumab therapy, and 68.4% (54/79) attained complete immunological remission (<2 U/mL). Obinutuzumab demonstrates high clinical remission rates and acceptable safety in PMN patients, with good efficacy even in refractory and RTX-resistant patients.
2026-07-11 | Artificial intelligence in membranous nephropathy: transforming clinical management toward precision medicine.
Membranous Nephropathy (MN) is the leading cause of primary nephrotic syndrome in adults, characterized by significant clinical heterogeneity ranging from spontaneous remission to end-stage kidney disease. Current management of membranous nephropathy, which relies heavily on renal biopsy and static serological markers such as anti-PLA2R antibodies, often fails to predict individual disease trajectories. This limitation frequently leads to empirical immunosuppressive therapy with a trial-and-error approach. This review explores the transformative potential of Artificial Intelligence (AI) in reshaping MN management from evidence-based to data-driven and predictive medicine. We examine AI-driven innovations across the clinical spectrum: from computational pathology systems that automate glomerular morphometry with high objectivity and reproducibility, to non-invasive diagnostic models integrating radiomics and serology for non-invasive diagnosis. In therapeutics, we discuss machine learning algorithms that predict individual responses to Rituximab versus Cyclophosphamide, enabling personalized regimen selection. Furthermore, we highlight the role of AI in prognostic stratification, where dynamic in silico patient models and multi-omics integration unravel molecular subtypes and forecast renal survival with high granularity. While acknowledging critical challenges such as data silos, model interpretability gaps, and the need for global validation, we conclude that AI serves as a powerful augmentation tool. By synthesizing high-dimensional data into actionable insights, AI has the potential to facilitate increasingly predictive, preventative, and personalized care strategies in MN management.
2026-07-10 | Real-World Long-term Comparisons of Rituximab versus Calcineurin Inhibitors for Membranous Nephropathy in the Cure Glomerulonephropathy Study.
Clinical trials in rare glomerular disease may establish short-term treatment efficacy but are limited by small sample sizes and short study duration. Observational data are needed to assess longer-term outcomes and can provide insights into real-world prescribing practices. This study applied modern statistical methods to real-world data from the Cure Glomerulonephropathy (CureGN) network to compare the effectiveness of rituximab and calcineurin inhibitors on long-term primary membranous nephropathy outcomes. CureGN participants with biopsy-confirmed primary membranous nephropathy who initiated either of the two treatments at least 6 months after any previous immunosuppressant exposure were eligible. Inverse-probability-of-treatment weighting balanced covariates at treatment initiation. Inverse-probability-of-censoring weights accounted for censoring individuals if another immunosuppressant was started during follow-up. Outcomes included time from treatment initiation to composite kidney disease progression (40% decline in eGFR, kidney replacement therapy, or eGFR <15), proteinuria remission, and relapse following remission. Hazard ratios and differences in restricted mean survival times were estimated. 325 treatment initiations across 250 unique participants were eligible, with median follow-up 53 months (25th-75th percentile: 24-79). Participants on calcineurin inhibitors had significantly higher risks of disease progression (HR=2.81; 95% CI: 1.16, 6.80). Hazard ratios for proteinuria remission (HR=0.77; 95% CI: 0.50, 1.17) and relapse (HR=1.42, 95% CI: 0.69, 2.92) had wide confidence intervals. Rituximab was associated with better kidney function preservation than calcineurin inhibitors over long follow-up. Proteinuria remission and relapse results favored rituximab but did not reach statistical significance. Long-term treatment comparative effectiveness in rare diseases can be evaluated with real-world data.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
12 orphan drug designations for Primary membranous glomerulonephritis.
12 orphan drug designations for Primary membranous glomerulonephritis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Povetacicept | antibodies | EMA | 2026-02-23 | — | Vertex Pharmaceuticals (Ireland) Limited |
povetacicept | proteins | FDA | 2026-01-22 | — | Vertex Pharmaceuticals Incorporated |
Felzartamab | antibodies | EMA | 2025-11-21 | — | Biogen Netherlands B.V. |
zanubrutinib | small molecules | FDA | 2024-05-20 | — | BeOne Medicines USA, Inc. |
Rituximab | antibodies | EMA | 2023-07-25 | — | 4p-Pharma |
Corticotropin (ACTH) porcine (synthetic) | proteins | FDA | 2023-06-21 | — | Cerium Pharmaceuticals, Inc. |
felzartamab | antibodies | FDA | 2023-05-17 | — | Human Immunology Biosciences |
rituximab | antibodies | FDA | 2023-01-26 | — | Mabion S.A. |
Budoprutug | antibodies | FDA | 2023-01-12 | — | Climb Bio, Inc. |
Mizoribine | small molecules | FDA | 2020-11-09 | — | RNR BioMedical Inc. |
obinutuzumab | antibodies | FDA | 2020-06-08 | — | Genentech, Inc., A Member of the Roche Group |
eculizumab | antibodies | FDA | 2001-03-05 | — | Alexion Pharmaceuticals, Inc. |
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