FELZARTAMAB FOR IGA NEPHROPATHY: FINAL RESULTS OF THE IGNAZ STUDY

Introduction:

Felzartamab is a monoclonal antibody that binds to CD38 on plasma cells–the likely source of pathogenic Gd-IgA1 and autoantibodies in IgA nephropathy (IgAN). The randomized, double-blind, placebo-controlled phase 2a IGNAZ study assessed the efficacy and safety of felzartamab vs placebo (PBO) in patients with IgAN. Final 24-month data are reported.

Methods:

Patients aged 18−80 years with biopsy-confirmed IgAN, proteinuria ≥1.0 g/d (≥0.5 g/d for Japanese patients), and eGFR ≥30 mL/min per 1.73m2 using renin-angiotensin inhibitors ≥3 months were randomized 1:1:1:1 in Part 1 to PBO (n=12) or felzartamab in 1 of 3 arms: 2 doses in 15 days (M1; n=12), 5 doses in 2 months (M2; n=11), and 9 doses in 5 months (M3; n=13). In Part 2, 6 Japanese patients received open-label M3.

Results:

Patients were 67% men, with a mean age of 41.6 years, UPCR of 1.7 g/g, and eGFR of 74.6 mL/min per 1.73m2. In Part 1, 40/48 patients completed treatment. Treatment with felzartamab led to rapid, clinically meaningful reductions in UPCR vs PBO, with the greatest effect in the M3 arm (Fig A). Mean eGFR declined less in the felzartamab arms vs PBO (Fig B). Among felzartamab arms, IgA reductions were rapid and durable (lasting 19 months after the last dose); IgG recovered by 6−9 months. Efficacy in Part 2 was similar to that of the Part 1 M3 arm. Treatment-emergent AEs were typically grade 1 or 2 and were not dose-dependent. The most common treatment-related AE was infusion-related reaction (IRR), usually on dose one. There was one treatment-related serious AE of IRR. Five patients discontinued felzartamab for IRR/hypersensitivity. The infection incidence was similar across felzartamab arms; all were grade 1 or 2 and non-serious.

Conclusions:

Felzartamab was generally well tolerated and led to sustained proteinuria reduction and reduced eGFR decline vs PBO, indicating potential disease modification in patients with IgAN. Investigation of felzartamab in patients at high risk for loss of kidney function is warranted.

This abstract was also submitted for ASN Kidney Week 2024 congress. 

I have potential conflict of interest to disclose.
Human Immunology Biosciences, Inc., a Biogen Company

I did not use generative AI and AI-assisted technologies in the writing process.