LONG-TERM RESULTS FROM THE ORIGIN PHASE 2B STUDY OF ATACICEPT FOR THE TREATMENT OF IGAN

Introduction:

B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in IgA nephropathy (IgAN) pathogenesis. Atacicept is a humanized TACI-Fc fusion protein that inhibits both BAFF and APRIL and is self-administered at home by subcutaneous injection. The ORIGIN Phase 2b study met the primary endpoint with a statistically significant and clinically meaningful UPCR reduction compared to placebo at 24 weeks, with a further reduction and eGFR stabilization through 36 weeks. This analysis reports 96-week results from the open-label extension (OLE).

Methods:

Participants with IgAN who received atacicept or placebo in a 36-week Phase 2b, randomized, blinded study period were enrolled in an OLE and received atacicept 150 mg for an additional 60 weeks. Key efficacy outcomes were changes in galactose-deficient IgA1 (Gd-IgA1), percentage of participants with hematuria, UPCR, and eGFR over 96 weeks. Long-term safety data were also evaluated.

Results:

There were 113 participants who received ≥1 atacicept dose. Over 96 weeks, there were sustained reductions (mean ±SE) in Gd-IgA1 (-65.9% ±1.7%), the percentage of participants with hematuria (-75.0%, 95% CI -87.3, -58.8; in participants with baseline hematuria), and UPCR (-52.2% ±4.7%). Importantly, long-term eGFR was maintained near baseline levels with a mean annualized slope of -0.6 ±0.5 mL/min/1.73m2/year at 96 weeks (Figure). Safety data showed atacicept was generally well tolerated.

Conclusions:

Gd-IgA1, hematuria, and UPCR reductions 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(1) supports the potential of atacicept to decrease the high lifetime risk of kidney failure in patients with IgAN.

1.      Baba M. PLoS One 2015.

This abstract was also submitted for 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.