Back
IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide, with up to 50% of patients progressing to ESKD or death within 20 years.(1,2) B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) play an important role in the maturation, differentiation, and effector function of B cells and plasma cells, leading to the elevated serum levels of galactose-deficient IgA1 (Gd-IgA1), anti-Gd-IgA1 autoantibodies, and immune complex formation that are central to IgAN pathogenesis. Atacicept, a dual BAFF/APRIL inhibitor, has been shown to reduce circulating levels of Gd-IgA1, anti-Gd-IgA1, and immune complexes, and is a potential disease-modifying approach to treating IgAN.
Two Phase 2 studies (JANUS [NCT02808429] and ORIGIN [NCT04716231]) evaluated safety and efficacy of atacicept vs placebo in IgAN. In ORIGIN, atacicept 150 mg showed placebo-adjusted UPCR reductions of 35% (p=0.012; intent-to-treat analysis) and 43% (p=0.003; prespecified per-protocol analysis) with eGFR stabilization (+1.6% change from baseline vs -8.5% for placebo; p=0.038) at 36 weeks. Safety was comparable between atacicept and placebo.
1. Kwon CS. J Health Econ Outcomes Res 2021
2. Pitcher D. Clin J Am Soc Nephrol 2023
ORIGIN 3 is a global, randomized, double-blind, placebo-controlled Phase 3 trial evaluating safety and efficacy of atacicept 150 mg for treatment of IgAN. Eligible patients are adults with biopsy-proven IgAN and persistent proteinuria despite stable and maximum-tolerated renin-angiotensin system inhibitor (RASi) regimen for ≥12 weeks (see figure for key entry criteria). 376 patients globally will be randomized 1:1 to self-administered subcutaneous atacicept 150 mg or placebo for 104 weeks in a double-blind period, followed by a 52-week open-label extension.
The primary endpoint is UPCR % change from baseline at 36 weeks analyzed using a mixed-effects model with repeated measurement. The key secondary endpoint is annualized eGFR slope up to 104 weeks.
This pivotal Phase 3 study will further evaluate atacicept’s disease-modifying potential as a treatment for IgAN.
This abstract was also submitted for ASN Kidney Week 2023. By submitting the abstract to WCN’24, abstract authors declare that re-submitting the abstract is permitted by the organizers of the previous meeting.