Subcutaneous mezagitamab, an investigational anti-CD38 monoclonal antibody, kept kidney function stable and proteinuria reduced in adults with IgA nephropathy through week 96, about 1.5 years after the final dose, according to final phase 1b results.1
The final analysis, published in Kidney International Reports, extends interim data Takeda presented at ASN Kidney Week 2025, where the company reported stable eGFR 18 months after treatment.1,2 Investigators noted recently approved IgA nephropathy therapies still leave a need for tolerable, disease-modifying agents with effects sustained off therapy.1 Mezagitamab depletes CD38-expressing plasma cells and plasmablasts, the cells responsible for producing galactose-deficient IgA1 (Gd-IgA1), while largely sparing overall B-cell counts.1
“Mezagitamab targeted the underlying immune mechanisms of IgA nephropathy, with data showing that kidney function remained stable in patients after the last dose of treatment,” said Jonathan Barratt, MD, PhD, Mayer Professor of Renal Medicine, University of Leicester, and principal investigator of the study, in a November 2025 statement from Takeda.2
Mezagitamab phase 1b trial design and proteinuria results in IgAN
The multicenter, open-label, single-arm phase 1b study (NCT05174221) enrolled 17 adults with biopsy-proven IgA nephropathy, UPCR of at least 1 g/g, and eGFR of at least 45 mL/min/1.73 m² despite stable renin-angiotensin system blockade.1 Participants received subcutaneous mezagitamab 600 mg once weekly for 8 weeks, then 600 mg every 2 weeks for 16 weeks, for 16 total doses.1 Those with a favorable proteinuria response by week 48 entered a 48-week observation period without further dosing.1
At baseline, mean age was 40.8 years, mean 24-hour UPCR was 1.5 g/g, and mean eGFR was 74.0 mL/min/1.73 m².1 Overall, 94.1% (16/17) of participants were taking an ACE inhibitor or ARB, and 35.3% (6/17) were also taking an SGLT2 inhibitor.1 All 17 participants completed the main study, and 13 entered the long-term observation period.1
Proteinuria fell within weeks of the first dose. The model-based geometric mean change in 24-hour UPCR from baseline was −54.3% at week 48 (95% CI, −65.7 to −39.1) and −53.4% at week 96 (95% CI, −72.6 to −20.7; n = 13).1 Mean change in eGFR from baseline was +1.9 mL/min/1.73 m² (95% CI, −2.0 to +5.8) at week 48 and +3.2 mL/min/1.73 m² (95% CI, −1.1 to +7.5; n = 13) at week 96.1
Mezagitamab safety, Gd-IgA1 depletion, and hematuria through week 96
The primary end point was the proportion of participants with adverse events (AEs) through week 96. Any AE occurred in 94.1% (16/17) of participants, and 17.6% (3/17) had a grade ≥3 AE, with 1 event, decreased white blood cell count, considered related to mezagitamab.1 No serious AEs, discontinuations due to AEs, grade ≥3 infections, or opportunistic infections were reported.1
Upper respiratory tract infection was the most common AE (47.1% [8/17]), followed by COVID-19, nasopharyngitis, oropharyngeal pain, and pyrexia (23.5% [4/17] each).1 Injection-related reactions generally occurred with the first dose and were mild; 3 grade 1 events coded as cytokine release syndrome were limited to fever or constitutional symptoms, which investigators considered more consistent with injection-related reactions.1 Treatment-emergent antidrug antibodies developed in 23.5% (4/17) of participants without apparent effect on pharmacokinetics.1
Serum Gd-IgA1 declined by 61.7% at week 24 and remained 50.9% below baseline at week 96 (95% CI, −61.1 to −33.5).1 In contrast, IgA partially recovered to −28.4% from baseline by week 96, while IgG and IgM returned to baseline levels.1 Among participants with baseline hematuria, 60% (6/10) had resolution at week 96.1
The investigators described the persistent Gd-IgA1 depletion alongside IgA recovery as a pattern not previously reported, contrasting it with sustained UPCR reductions seen with intravenous felzartamab, another anti-CD38 antibody, in a phase 2a study.1 They cited the lack of a comparator arm and the small sample, not powered for efficacy, as key limitations.1
Takeda is evaluating mezagitamab in a pivotal phase 3 trial in primary IgA nephropathy (NCT06963827), alongside a phase 3 program in chronic immune thrombocytopenia.1,2 The European Medicines Agency granted mezagitamab Orphan Drug Designation for primary IgA nephropathy in October 2025.2 HCPLive previously covered the 48-week interim data Barratt presented at the 2025 European Renal Association Congress.3
References
Barratt J, Kim DK, Park I, et al. Clinical trial of open-label mezagitamab in IgAN: final 96-week results. Kidney Int Rep. Published online October 7, 2026. doi:10.1016/j.ekir.2026.107128
Takeda. Takeda presents new data showing mezagitamab (TAK-079) sustained effect on kidney function 18 months after treatment in primary IgA nephropathy. Published November 7, 2025. Accessed October 22, 2026. https://www.takeda.com/newsroom/newsreleases/2025/new-data-mezagitamab/
