Vera Therapeutics (NASDAQ: VERA) has announced positive 96-week data from its ORIGIN Phase 2b trial, revealing that atacicept effectively stabilized kidney function in patients with immunoglobulin A nephropathy (IgAN). The findings, presented at the American Society of Nephrology Kidney Week 2024, highlight the potential of atacicept to modify the course of IgAN, a leading cause of kidney failure. The study demonstrated significant reductions in key disease markers and a favorable safety profile, reinforcing atacicept's promise as a novel therapeutic option.
Key Efficacy Outcomes
The ORIGIN Phase 2b trial showcased notable improvements across several critical endpoints. Patients treated with atacicept experienced a 66% reduction in galactose-deficient IgA1 (Gd-IgA1), a hallmark of IgAN. Additionally, 75% of participants achieved resolution of hematuria, and there was a 52% reduction in proteinuria. Most significantly, the mean annualized estimated glomerular filtration rate (eGFR) slope was -0.6 mL/min/1.73m2/year, indicating a stabilization of kidney function comparable to that of healthy individuals. According to Dr. Jonathan Barratt, Mayer Professor of Renal Medicine at the University of Leicester, this conversion of patients from an eGFR profile of decline to one consistent with the general population is a “differentiated and compelling finding.”
Safety and Completion Rates
The trial maintained a high completion rate of 90%, underscoring the tolerability and patient adherence to atacicept treatment. The safety profile remained consistent with previous observations, further supporting its potential as a long-term therapy.
Path to Phase 3 and Regulatory Submission
Marshall Fordyce, M.D., Founder and CEO of Vera Therapeutics, expressed enthusiasm about the long-term efficacy and safety data, emphasizing atacicept's potential to address the underlying pathogenesis of IgAN. The company anticipates topline results from the Phase 3 ORIGIN 3 trial in Q2 2025, with plans for a Biologics License Application (BLA) submission to the U.S. FDA later that year. This regulatory pathway could pave the way for atacicept to become a transformative therapy in the IgAN market.
Expansion into Additional Indications
Vera Therapeutics is also planning to initiate the PIONEER study in 2025 to evaluate the efficacy and safety of atacicept in expanded IgAN populations, including those with low kidney function, high proteinuria, or IgAN recurrence after kidney transplant. Furthermore, the PIONEER study will explore atacicept's potential in other autoimmune glomerular diseases, such as primary membranous nephropathy.
About the ORIGIN Trials
The Phase 2b ORIGIN trial (NCT04716231) was a global, multicenter, randomized, double-blind, placebo-controlled study involving 116 IgAN patients at high risk of disease progression. The Phase 3 ORIGIN 3 trial is designed to assess the impact of atacicept on proteinuria and kidney function preservation compared to placebo.
Mechanism of Action
Atacicept is an investigational recombinant fusion protein that binds to B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), cytokines involved in B-cell survival and autoantibody production. By blocking these cytokines, atacicept aims to reduce autoantibody levels and modify the course of autoimmune diseases like IgAN.
