Results of Open-Label Extension of the ORIGIN Phase 2b Study of Atacicept 

Researchers have identified B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) as key factors in the pathogenesis of IgA nephropathy (IgAN). During a late-breaking oral session at ASN Kidney Week 2024, Jonathan Barratt, PhD, of the University of Leicester, Leicester, United Kingdom, presented long-term results from the ORIGIN study. The presentation was titled Long-Term Results From the ORIGIN Phase 2b Study of Atacicept for the Treatment of IgA Nephropathy (IgAN).

Atacicept is a humanized TACI-Fc fusion protein that inhibits BAFF and APRIL. It is self-administered subcutaneously at home. The primary endpoint of the ORIGIN phase 2b study was met at week 24 with a statistically significant and clinically meaningful reduction in urine protein-creatinine ratio (UPCR) versus placebo. There was additional reduction and stabilization in eGFR over 36 weeks. The late-breaking session reported 96-week results from the open-label extension (OLE).

Study participants with IgAN in either the atacicept or placebo arm in the 36-week phase 2b, randomized, blinded study period were enrolled in the OLE and received atacicept 150 mg for an additional 60 weeks. Efficacy outcomes of interest were changes in galactose-deficient IgA1 (Gd-IgA1), percentage of participants with hematuria, UPCR, and eGFR over 96 weeks. The researchers also examined long-term safety data.

The OLE cohort included 113 patients who received ≥1 dose of atacicept. During the 96-week period, there were sustained reductions in Gd-IgA1 (–65.9%), and in the percentage of participants with hematuria (–75.0% in those with hematuria at baseline) and UPCR (–52.2%). Of note, long-term eGFR remained stable at near baseline levels (mean annualized sloe of –0.6 mL/min/1.73 m²/year at 96 weeks).

Analysis of safety data demonstrated that atacicept was generally well tolerated.

In summary, the authors said, “Gd-IgA1, hematuria, and UPCR reduction with eGFR stabilization through 96 weeks demonstrate that atacicept offers a potentially safe, long-term, disease-modifying treatment for IgAN. Specifically, the conversion of an eGFR profile in patients with IgAN from one of steady decline to one representative of the general population without kidney disease [Baba M. Plos One. 2015.] supports the potential of atacicept to decrease the high lifetime risk of kidney failure in patients with IgAN.”

Source: Barratt J, Barbour S, Brenner RM, et al. Long-term results from the ORIGIN phase 2b study of atacicept for the treatment of IgA nephropathy (IgAN). SA-OR102. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2024; October 26, 2024; San Diego, California. Funding for the study was provided by Vera Therapeutics, Inc.