Abstract: FR-PO857
Safety, Tolerability, and Efficacy of Mezagitamab (TAK-079) as Add-On to Standard of Care Therapy in Individuals with Primary IgA Nephropathy: Interim Results from an Open-Label Phase 1b Study
Session Information
- IgA Nephropathy: Clinical, Outcomes, and Therapeutics
October 25, 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
- Barratt, Jonathan, Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
- Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Nguyen, Van Anh, Takeda Development Center Americas Inc, Cambridge, Massachusetts, United States
- Dobler, Iwona, Takeda Development Center Americas Inc, Cambridge, Massachusetts, United States
- Li, Cheryl, Takeda Development Center Americas Inc, Cambridge, Massachusetts, United States
- Farmer, MK, Takeda Development Center Americas Inc, Cambridge, Massachusetts, United States
Background
IgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis worldwide and is associated with a poor prognosis including progression to end-stage kidney disease or death in some cases. Therapeutic options for IgAN are limited. Mezagitamab, a fully human anti-CD38 IgG1 monoclonal antibody, depletes plasma cells, plasmablasts, and natural killer cells expressing CD38. Mezagitamab depletes cells that produce galactose-deficient IgA1 (Gd-IgA1) and autoantibodies, which results in decreased immune complex formation, potentially reducing proteinuria/promoting stabilization of kidney function over time.
Methods
This open-label, single-arm, phase 1b, multicenter study (NCT05174221), evaluated mezagitamab as an add-on to standard of care therapy (ACEi, ARB) in IgAN. Eligible participants had biopsy-proven disease/proteinuria by urine protein to creatinine ratio (UPCR) ≥1 mg/mg or urine protein excretion (UPE) ≥1 g/24 hours, despite optimized renin-angiotensin-aldosterone system therapy. Participants received subcutaneous mezagitamab 600 mg once weekly for 8 weeks, then 600 mg every 2 weeks for 16 weeks (16 total doses). Primary endpoint was percentage of participants with treatment emergent adverse events (TEAEs). Secondary and exploratory endpoints included serum IgA and Gd-IgA1 levels, percentage change from baseline in UPCR, and change from baseline in eGFR. Results are from a prespecified interim analysis.
Results
Seventeen participants enrolled (mean age 40.8 years, 53% female, 71% Asian). No serious TEAEs, discontinuations due to TEAEs, grade ≥3 infectious TEAEs, or opportunistic infections were reported. Most common TEAEs were upper respiratory tract infection (35.3%), pyrexia (23.5%), and oropharyngeal pain (23.5%). There were rapid and sustained reductions from baseline levels in serum IgA (nadir −70.1%) and Gd-IgA1 (nadir −62.2%). At Week 36, a 54.9% mean reduction in proteinuria (UPCR) was observed. Renal function (eGFR) remained stable though Week 36.
Conclusion
Mezagitamab was generally well tolerated as an add-on to standard of care therapy. Rapid and sustained reductions in UPCR, serum IgA, and Gd-IgA1 levels were seen with stable eGFR.
Funding
- Commercial Support – Takeda Pharmaceutical Company Limited