Takeda's Mezagitamab Shows Sustained Kidney Protection 18 Months After Treatment in IgA Nephropathy
核心洞察
Takeda (搜索)'s Phase 1b study demonstrates that mezagitamab (TAK-079) maintains stable kidney function in IgA nephropathy (搜索) patients through Week 96, 18 months after the last dose.
The anti-CD38 (搜索) monoclonal antibody sustained a 55.2% reduction in proteinuria and 50.1% reduction in Gd-IgA1 (搜索) levels with no serious adverse events reported.
Mezagitamab has received FDA Breakthrough Therapy Designation for immune thrombocytopenia (搜索) and EMA Orphan Drug Designation for IgA nephropathy (搜索).
Takeda (搜索) announced promising long-term data for mezagitamab (TAK-079), an investigational anti-CD38 (搜索) monoclonal antibody, showing sustained kidney function protection in patients with primary IgA nephropathy (搜索) 18 months after completing treatment. The results from the Phase 1b study were presented at the American Society of Nephrology Kidney Week 2025 in Houston.
Sustained Clinical Benefits After Treatment Completion
The open-label, proof-of-concept study followed 13 patients with IgA nephropathy (搜索) through Week 96, demonstrating that kidney function remained stable with a mean change in estimated glomerular filtration rate (eGFR) from baseline of +2.5 (95% CI: −1.8, +7.6; n=12). Patients sustained a 55.2% mean reduction in proteinuria measured by urine protein-creatinine ratio (95% CI: 30.2, 72.6; n=13) and achieved a 50.1% reduction in Gd-IgA1 (搜索) levels, the abnormal protein implicated in disease pathogenesis.
"Mezagitamab targeted the underlying immune mechanisms of IgA nephropathy (搜索), with data showing that kidney function remained stable in patients after the last dose of treatment," said Prof. Jonathan Barratt, M.D., Ph.D., principal investigator for the Phase 1b study. "This is especially critical given the progressive and often silent nature of the disease, with many patients already experiencing some degree of kidney damage by the time they're diagnosed."
Favorable Safety Profile Maintained
The study reported no serious adverse events, opportunistic infections, or grade ≥3 infections through Week 96. No serious hypersensitivity or injection-related reactions or discontinuations due to adverse events were observed. Hematuria resolved in 60% of patients by Week 96, and complete recovery toward baseline in IgG levels was observed.
Addressing Critical Unmet Medical Need
IgA nephropathy (搜索) is a lifelong progressive autoimmune disease often diagnosed in young people aged 10-30 years that causes irreversible kidney damage. The disease has no cure, and approximately one in five patients experience renal failure within 10 years of diagnosis despite available treatments. Mezagitamab works by depleting cells that produce Gd-IgA1 (搜索), targeting early steps in the disease process.
Phase 3 Development and Regulatory Recognition
Mezagitamab is currently in Phase 3 clinical development for both primary IgA nephropathy (搜索) (NCT06963827) and chronic immune thrombocytopenia (搜索) (NCT06722235), with patient enrollment ongoing. The drug received Orphan Drug Designation from the European Medicines Agency for primary IgA nephropathy in October 2025 and Breakthrough Therapy Designation from the FDA for chronic immune thrombocytopenia in August 2025.
"These promising data reinforce our belief in the potential of mezagitamab to redefine how autoimmune diseases like IgA nephropathy (搜索) are treated – by targeting their root cause," said Obi Umeh, M.D., M.Sc., Vice President, Franchise Global Program Leader at Takeda (搜索).
Study Design and Patient Population
The Phase 1b trial (NCT05174221) enrolled 17 patients with biopsy-proven IgA nephropathy (搜索) and proteinuria with urine protein-to-creatinine ratio ≥1 g/g and eGFR ≥45 mL/min/1.73m². Participants received subcutaneous mezagitamab 600 mg once weekly for 8 weeks, then 600 mg every two weeks for 16 weeks (16 total doses), followed by safety follow-up periods.
Mezagitamab is a fully human, anti-CD38 (搜索) IgG1 monoclonal antibody that depletes cells highly expressing CD-38, including plasma cells, plasmablasts, and natural killer cells. This depletion is predicted to decrease immune complex formation, reduce inflammation and proteinuria, and promote kidney function stabilization over time.