POS-109 INTERIM RESULTS OF PHASE 1 AND 2 TRIALS TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND CLINICAL ACTIVITY OF BION-1301 IN PATIENTS WITH IgA NEPHROPATHY

Further Evidence for the Mucosal Origin of Pathogenic IgA in IgA Nephropathy

“…Indeed, early studies of targeted-release formulation (TRF) budesonide (the first US Food and Drug Administration-approved treatment for IgAN that specifically targets gut-associated lymphoid tissue), BION-1301 (an anti-APRIL mAb), and atacicept (a recombinant fusion protein containing the binding portion of transmembrane activator and CAML interactor (TACI) that inhibits both BAFF and APRIL) have each been demonstrated to reduce GdIgA1 levels in IgAN. [7][8][9] In contrast, depletion of peripheral CD20 1 B cells with rituximab did not affect GdIgA1 levels, which is likely due to GdIgA1-secreting plasma cells not being targeted by this approach. 10 Further characterization of circulating GdIgA1 1 B-cell populations, as well as improving our understanding of the pathogenesis, could eventually lead to their use as a biomarker to assess response to therapy or to the identification of new therapeutic targets.…”

A PRoliferation-Inducing Ligand (APRIL) in the Pathogenesis of Immunoglobulin A Nephropathy: A Review of the Evidence

“…Zigakibart (BION-1301), a humanized IgG4 anti-APRIL monoclonal antibody, was evaluated in an open-label phase I study in healthy volunteers and was reported to be well tolerated, while providing dose-dependent and durable reductions in serum levels of free APRIL, IgA and Gd-IgA1, and IgM [111]. Although a phase I/II study in multiple myeloma (NCT03340883) was terminated early due to a lack of response, the interim results from another small phase I/II open-label study in patients with IgAN demonstrated that zigakibart administered every 2 weeks was well tolerated for at least 12 weeks and produced reductions in serum levels of immunoglobulins, free APRIL, and proteinuria [111]. A phase III study in adults with IgAN (NCT05852938) is currently enrolling.…”

“…Currently, the efficacy data for both anti-APRIL monoclonal antibodies and dual APRIL/BAFF fusion protein antagonists appear positive [111,113,114,116]. Thus far, the safety signals have also been reassuring.…”

Targeting APRIL in the Treatment of IgA Nephropathy

“…Zigakibart (BION-1301) is being studied in a single-arm phase 1/2 trial of up to 40 patients with IgA nephropathy (NCT03945318). 10 Significant reductions in free APRIL, serum IgA, and Gd-IgA1 have been reported, with a mean reduction of 54% in proteinuria observed at week 24 compared with baseline, and this agent will be studied in a forthcoming phase 3 trial (BEYOND; NCT05852938). Atacicept is a fusion protein that contains the extracellular portion of TACI, hence binding and inhibiting both APRIL and BAFF.…”