Vera Therapeutics has announced positive results from their Phase 2b ORIGIN clinical trial for atacicept, a novel investigational drug for IgA nephropathy (IgAN). The findings, presented at the 61st European Renal Association (ERA) Congress, demonstrate significant reductions in proteinuria, stabilization of kidney function, and favorable safety profiles, marking a potential breakthrough in the treatment of this progressive autoimmune kidney disease.
Key Findings from the ORIGIN Trial
The Phase 2b ORIGIN trial (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled study that evaluated the safety and efficacy of atacicept in 116 patients with IgAN who continued to have persistent proteinuria despite being on a stable regimen of renin-angiotensin-aldosterone system inhibitors (RAASi) for at least 12 weeks. The trial focused on multiple endpoints to assess atacicept’s impact on the disease.
Primary and Secondary Endpoints Achieved:
- Proteinuria Reduction: The primary endpoint was met with a statistically significant reduction in proteinuria at week 24. Patients in the atacicept 75/150 mg groups showed a 31% mean reduction from baseline (p=0.037 versus placebo). By week 36, the atacicept 150 mg group exhibited a 33% mean reduction in proteinuria (p=0.047 versus placebo).
- eGFR Stabilization: Exploratory analyses demonstrated stabilization of estimated glomerular filtration rate (eGFR), with the atacicept group showing a minimal decline in eGFR compared to placebo through 24 weeks.
- Reduction in Gd-IgA1: Atacicept robustly reduced levels of galactose-deficient IgA1 (Gd-IgA1), a key pathogenic factor in IgAN, from baseline through 24 weeks.
Safety and Tolerability:
Atacicept was generally well-tolerated with a safety profile comparable to placebo. There were low rates of serious adverse events (2%) and no significant increase in infection rates.
These findings align with previous studies involving over 1,500 participants across different indications, reinforcing atacicept’s potential as a safe long-term treatment option.
Transition to Phase 3: ORIGIN 3 Trial
Encouraged by the Phase 2b results, Vera Therapeutics has initiated the Phase 3 ORIGIN 3 trial to further evaluate atacicept 150 mg in a larger patient population over a longer period. This pivotal trial includes a 104-week double-blind treatment period followed by a 52-week open-label extension, focusing on long-term proteinuria reduction and kidney function preservation.
About IgA Nephropathy
IgA nephropathy, also known as Berger’s disease, is a serious autoimmune disease where IgA antibodies deposit in the kidneys, causing inflammation and damage. It can progress to end-stage kidney disease (ESKD) or kidney failure in up to 50% of patients, highlighting the urgent need for effective treatments. Current therapies mainly manage symptoms and slow progression, underscoring a significant unmet need.
About Atacicept
Atacicept is an investigational recombinant fusion protein that inhibits B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL). These cytokines are crucial for B-cell survival and autoantibody production, playing a significant role in autoimmune diseases. By targeting these pathways, atacicept aims to reduce the formation of pathogenic immune complexes in IgAN and other autoimmune conditions like lupus nephritis.
Vera Therapeutics’ Mission and Future Directions
Vera Therapeutics, a late-stage biotechnology company, focuses on developing treatments for serious immunological diseases. Their lead product candidate, atacicept, has shown promising results in reducing autoantibodies and stabilizing kidney function. Vera is committed to advancing atacicept through the Phase 3 ORIGIN 3 trial, aiming to provide a new standard of care for patients with IgAN and potentially other autoimmune diseases.
Looking Forward
The positive outcomes from the Phase 2b ORIGIN trial highlight atacicept’s potential to significantly improve clinical outcomes for patients with IgA nephropathy. As the Phase 3 ORIGIN 3 trial progresses, the medical community remains hopeful that atacicept could transform the treatment landscape for this debilitating kidney disease.
