Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy

<h4>Introduction</h4><p dir="ltr">Zigakibart is a humanized IgG4 monoclonal antibody that binds the cytokine A Proliferation-Inducing Ligand (APRIL also known as TNFSF13). APRIL is a critical factor in immunoglobulin (Ig) A nephropathy (IgAN) pathogenesis.</p><h4>Methods</h4><p dir="ltr">Here, we report healthy volunteer (63 overall) and 100-week data from an ongoing Phase 1/2 clinical trial in 40 patients with IgAN (NCT03945318) treated with zigakibart.</p><h4>Results</h4><p dir="ltr">In health volunteers, zigakibart was well tolerated following intravenous administration of single doses ranging from 10-1350 mg or multiple doses ranging from 50-450 mg every two weels. Zigakibart exposure increased in a dose-proportional manner, with corresponding durable reductions in levels of free APRIL, IgA and IgM, and to a lesser extent, IgG. In patients with IgAN, zigakibart 600 mg, administered subcutaneously every two weeks, was well tolerated with no treatment-emergent adverse events leading to study drug discontinuation or death. A 60% reduction in proteinuria and sustained estimated glomerular filtration rate stabilization was observed at week 100. There was a notable decrease in hematuria, as well as rapid and durable reductions in IgA, galactose-deficient IgA (Gd-IgA1), and IgM levels, with a modest reduction in IgG.</p><h4>Conclusions</h4><p dir="ltr">Overall, zigakibart demonstrated robust pharmacological activity, and clinical evidence shows an acceptable safety profile with clinically meaningful proteinuria reduction and sustained estimated glomerular filtration rate stabilization in patients with IgAN, providing a potentially disease-modifying approach for the treatment of IgAN. The effects of zigakibart on proteinuria and long-term kidney function in adults with IgAN are being evaluated in the ongoing Phase 3 BEYOND study (NCT05852938).</p>