Takeda has announced new interim data from its Phase 1b, open-label, proof-of-concept study of mezagitamab (TAK-079), a subcutaneous anti-CD38 monoclonal antibody, in patients with primary immunoglobulin A (IgA) nephropathy. Results presented at the American Society of Nephrology (ASN) Kidney Week 2025 showed that kidney function remained stable through Week 96—up to 18 months after the final dose of mezagitamab.
Sustained Kidney Function and Proteinuria Reduction
Among the 17 patients enrolled, 13 continued into long-term follow-up. At Week 96, kidney function remained stable (mean change in eGFR from baseline +2.5; 95% CI: -1.8, +7.6; n=12) and proteinuria, measured via urine protein-creatinine ratio (UPCR), showed a 55.2% mean reduction (95% CI: 30.2, 72.6; n=13).
Sustained reductions in disease-related biomarkers were also observed, including a 50.1% decrease in galactose-deficient IgA1 (Gd-IgA1) and normalization of serum IgG levels by Week 96. Hematuria resolved in 60% of patients.
“Mezagitamab targeted the underlying immune mechanisms of IgA nephropathy, with data showing that kidney function remained stable even after treatment ended,” said Prof. Jonathan Barratt, M.D., Ph.D., principal investigator for the study. “Given the silent, progressive nature of IgA nephropathy, this durability is encouraging.”
Favorable Safety Profile
Mezagitamab was generally well tolerated, with no new safety concerns reported. No serious adverse events, discontinuations, hypersensitivity reactions, or grade ≥3 infections were observed throughout the 96-week study period.
Advancing Toward Late-Stage Development
Takeda is currently conducting Phase 3 trials of mezagitamab in both primary IgA nephropathy (NCT06963827) and chronic immune thrombocytopenia (NCT06722235). The therapy has received Orphan Drug Designation from the European Medicines Agency for IgA nephropathy and Breakthrough Therapy Designation from the U.S. FDA for chronic immune thrombocytopenia.
“These data reinforce our belief that mezagitamab could redefine treatment by addressing the root cause of IgA nephropathy,” said Obi Umeh, M.D., M.Sc., vice president and global program leader at Takeda. “We are advancing our Phase 3 programs with the goal of offering a disease-modifying therapy for patients with limited options.”
Study Overview
The Phase 1b trial (NCT05174221) was an open-label, single-arm, multicenter study evaluating mezagitamab as an add-on to stable background therapy in adults with biopsy-proven IgA nephropathy and proteinuria (UPCR ≥1 g/g).
Participants received mezagitamab 600 mg subcutaneously once weekly for 8 weeks, followed by dosing every two weeks for 16 weeks (16 total doses) and a 24-week safety follow-up. Responders at Week 48 entered a 48-week long-term follow-up.
Primary endpoints included adverse event frequency and severity, while secondary and exploratory endpoints assessed biomarker changes (IgA, IgG, Gd-IgA1), proteinuria, eGFR, and hematuria resolution.
About Mezagitamab
Mezagitamab is a fully human anti-CD38 IgG1 monoclonal antibody designed to deplete plasma cells, plasmablasts, and natural killer cells—key contributors to pathogenic immune complex formation in autoimmune diseases.
By reducing Gd-IgA1-producing cells, mezagitamab aims to decrease proteinuria, limit kidney inflammation, and stabilize renal function over time. The compound remains investigational and has not been approved by any regulatory authority.
