Introduction:
IgA nephropathy is a B-cell mediated disease associated with progressive loss of kidney function and a high lifetime risk of kidney failure. Current treatments fail to stop the decline in kidney function, highlighting the need for effective disease-modifying therapies. Atacicept is a fully humanized TACI-Fc fusion protein that binds and inhibits B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), the key cytokines that drive B-cell activation central to the pathogenesis of IgA nephropathy. Atacicept is currently in clinical development for IgAN treatment. The ORIGIN Phase 2b study met the primary endpoint demonstrating a statistically significant and clinically meaningful UPCR reduction with atacicept compared to placebo at 24 weeks, with a further reduction and eGFR stabilization through 36 weeks. At 96 weeks, the open-label extension period demonstrated sustained improvements in key markers that characterize disease modification, including reductions in galactose-deficient immunoglobulin A1 (Gd-IgA1), resolution of hematuria, reductions in UPCR, and stabilization of eGFR at a slope similar to that observed in the general population without kidney disease. Safety data showed atacicept was generally well tolerated.
Methods:
ORIGIN Extend is a global multicenter Phase 2 trial to evaluate long-term safety, tolerability, and efficacy of atacicept 150 mg for treatment of IgAN. Eligible participants must have completed the protocol-defined treatment period in a Vera-sponsored clinical trial of atacicept (ie, parent study). Participants will receive atacicept 150 mg self-administered at home via subcutaneous weekly injection for up to 3 years or until atacicept is commercially available in their region.
Results:
Endpoints include long-term safety and tolerability of atacicept and its effect on changes in Gd-IgA1, hematuria, proteinuria, and eGFR. This trial is ongoing.
Conclusions:
The ORIGIN Extend study will enable continued access to atacicept for participants of a parent study and provide extended long-term data on the disease-modifying potential of atacicept in IgAN.
This abstract was also presented at the ASN Kidney Week 2024 congress.
I have potential conflict of interest to disclose.
Sponsored by Vera Therapeutics, Inc.
I did not use generative AI and AI-assisted technologies in the writing process.