Vera Therapeutics announced positive 96-week data from its ORIGIN Phase 2b trial of atacicept in patients with immunoglobulin A nephropathy (IgAN), showcasing stabilized kidney function and sustained reductions in key disease markers. The data, presented at the American Society of Nephrology Kidney Week 2024 and published in the Journal of the American Society of Nephrology, highlight atacicept's potential to modify the disease's natural history and prevent kidney failure.
Jonathan Barratt, MD, PhD, FRCP, Mayer Professor of Renal Medicine at the University of Leicester, emphasized the clinical significance of the findings, stating, "Converting patients with IgAN from an eGFR profile of unrelenting decline to a profile consistent with the general population without kidney disease is a differentiated and compelling finding."
Key Findings from the ORIGIN Phase 2b Trial
The ORIGIN Phase 2b trial (NCT04716231) was a global, multicenter, randomized, double-blind, placebo-controlled study involving 116 IgAN patients who continued to exhibit persistent proteinuria despite receiving stable renin-angiotensin-aldosterone system inhibitor therapy. Participants were randomized to receive atacicept at 150 mg, 75 mg, or 25 mg, or a placebo weekly.
Over the 96-week study period, patients treated with atacicept demonstrated:
- A 66% reduction in galactose-deficient IgA1 (Gd-IgA1)
- Resolution of hematuria in 75% of participants
- A 52% reduction in proteinuria
- A mean annualized estimated glomerular filtration rate (eGFR) slope of -0.6 mL/min/1.73m2/year
The safety profile of atacicept remained consistent with previous observations, with a 90% completion rate.
Implications for IgAN Treatment
IgAN, also known as Berger's disease, is a leading cause of kidney failure, characterized by the accumulation of IgA antibodies in the kidneys. Current treatments primarily focus on managing symptoms and slowing disease progression. Atacicept, a recombinant fusion protein, targets B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), cytokines that promote B-cell survival and autoantibody production.
Marshall Fordyce, M.D., Founder and CEO of Vera Therapeutics, noted the significance of the 96-week data, stating, "The stabilization of kidney function through two years—the longest duration of data among B cell modulators to date—positions atacicept as a potential best- and first-in-class treatment option for patients with IgAN."
Ongoing and Future Studies
Vera Therapeutics is currently conducting the Phase 3 ORIGIN 3 trial (NCT04716231) to further evaluate the safety and efficacy of atacicept in IgAN patients. Topline results are expected in Q2 2025, with a planned Biologics License Application (BLA) submission to the U.S. FDA later in the year.
The company also plans to initiate the ORIGIN Extend study in Q4 2024 to provide continued access to atacicept for ORIGIN participants. Additionally, the PIONEER study is planned for 2025 to assess atacicept in expanded IgAN populations and other autoimmune glomerular diseases.
