Kidney Week 2025 Annual Meeting-Glomerular Targeted Therapies: The New Era

Video Transcription

Video Summary

This oral abstract session, “Glomerular targeted therapies: the new era,” highlighted multiple kidney disease treatments aimed at specific pathogenic pathways rather than broad immunosuppression.<br /><br />A phase 2 randomized, placebo-controlled trial tested BI764198, an oral selective TRPC6 inhibitor, in primary FSGS (12 weeks). Thirty-five percent of treated patients achieved ≥25% UPCR reduction versus 7% on placebo, with the best mean proteinuria reduction at 20 mg (≈38%). All four patients with TRPC6 gain-of-function variants receiving drug improved (placebo variant patients did not). Kidney function by cystatin C remained stable; adverse events were generally mild.<br /><br />A NEFIGARD subanalysis in IgA nephropathy evaluated sustained absolute proteinuria response (UPCR ≤1 g/g). After 9 months of targeted-release budesonide (Nefecon) then off-treatment follow-up, 72% maintained response ≥9 months and 46% ≥18 months (vs 38% and 21% placebo). Lower sustained proteinuria correlated with better eGFR preservation, raising questions about whether immunologic vs hemodynamic mechanisms confer different long-term benefits.<br /><br />In C3G/immune complex MPGN (VALIANT), the C3 inhibitor pegcetacoplan maintained ~67% proteinuria reduction at 52 weeks, with meaningful proportions reaching remission/normalization and relative eGFR stability compared with expected rapid decline.<br /><br />A post hoc phase 3 analysis in atypical HUS showed earlier ravulizumab (≤7 days) led to higher complete TMA response, faster eGFR improvement, and greater dialysis discontinuation than later treatment.<br /><br />A 96-week Asian lupus nephritis trial found tacrolimus+steroids had comparable efficacy to mycophenolate+steroids but different safety (more AKI with tacrolimus; more leukopenia/infectious SAEs with mycophenolate).<br /><br />Other talks covered zanubrutinib (BTK inhibition) showing strong anti-PLA2R reductions and proteinuria improvements in membranous nephropathy; GLP1R agonist–podocyte adhesion mechanisms in FSGS; long-acting MASP2 siRNA for IgA; and VCAM1-sensing “syn-notch” T cells enabling kidney-localized immunosuppression in crescentic GN models.

Asset Subtitle

Moderator(s): Rupali Avasare, Vimal Derebail

Presentation(s):

TRPC6 Inhibition for the Treatment of FSGS: Phase 2 Randomized Controlled Trial of BI 764198 - Nicholas Cross
Duration of Absolute Proteinuria Response with Nefecon in Patients with Primary IgAN: Results from the Two-Year NefIgArd Trial - Brad Rovin
Pegcetacoplan for 52 Weeks Results in Sustained Proteinuria Reduction to Remission (≤0.5 g/g) and Normalization (≤0.2 g/g): Phase 3 VALIANT Trial - Carla Nester
Ravulizumab in Atypical Hemolytic Uremic Syndrome: Time-to-Treatment Analysis from a Phase 3 Trial - Katherine Garlo
Prospective Randomized Controlled 96-week Study to Evaluate the Efficacy and Safety of Tacrolimus and Glucocorticoid as Continuous Induction-Maintenance Treatment for Class III/IV±V Lupus Nephritis - Tak Mao Chan
Zanubrutinib (zanu) in Anti-Phospholipase A2 Receptor (PLA2R)-Associated Primary Membranous Nephropathy (PMN): Preliminary Results of a Phase 2/3, Multicenter, Randomized, Open-Label Study - Richard Lafayette
Targeting Podocytopathy: Liraglutide Restores Podocyte Adhesion Homeostasis via GLP1R-CD151-Dependent Integrin Signaling in FSGS - Ying Fan
FB-7013: A Novel, Long-Duration siRNA Targeting Mannan-Binding Lectin Serine Protease 2 (MASP2) Exhibits Therapeutic Potential for Treatment of IgAN - Michael Wang
Spatially Controlled Immunosuppression with SynNotch T Cells for the Treatment of Kidney Autoimmunity - Tobias Eckey

Note: Continuing education credits are not being offered for this session.

Meta Tag

Date 11/8/2025

Pathway 1 Glomerular Diseases

Session ID 519872

Keywords

glomerular targeted therapies

primary FSGS

TRPC6 inhibitor BI764198

proteinuria reduction UPCR

TRPC6 gain-of-function variants

IgA nephropathy NEFIGARD

targeted-release budesonide Nefecon

eGFR preservation

C3 glomerulopathy immune complex MPGN

pegcetacoplan C3 inhibitor

atypical hemolytic uremic syndrome ravulizumab

lupus nephritis tacrolimus vs mycophenolate

membranous nephropathy zanubrutinib BTK anti-PLA2R