Atacicept is a first-in-class, dual anti-B-cell Activation Factor-A Proliferation-Inducing Ligand fusion protein in clinical evaluation for treatment of IgA nephropathy. To compare efficacy and safety of atacicept versus placebo in patients with IgAN, this randomized, double-blind, placebo-controlled phase 2b clinical trial ORIGIN enrolled 116 individuals with biopsy-proven IgA nephropathy. Participants were randomized to atacicept 150, 75, or 25 mg versus placebo once weekly for up to 36 weeks. Primary and key secondary endpoints were changes in urine protein creatinine ratio based on 24-hour urine collection at weeks 24 and 36, respectively, in the combined atacicept 150 mg and 75 mg group versus placebo. The primary endpoint was met at week 24 as the mean urine protein creatinine ratio was reduced from baseline by 31% in the combined atacicept group versus 8% with placebo, resulting in a significant 25% reduction with atacicept versus placebo. At week 36, the key secondary endpoint was met as the mean urine protein creatinine ratio reduced from baseline by 34% in the combined atacicept group versus a 2% increase with placebo, resulting in a significant 35% reduction with atacicept versus placebo. The reduction in proteinuria was accompanied by stabilization in endpoint eGFR with atacicept compared to a decline with placebo at week 36, resulting in significant between-group geometric mean difference of 11%, approximating an absolute difference of 5.7 mL/min/1.73m2. Endpoint galactose deficient IgA1 levels significantly decreased from baseline by 60% versus placebo. The safety profile of atacicept was like placebo. Thus, our results provide evidence to support a pivotal, phase 3 study of atacicept in IgA nephropathy.

Biostatistics Vera Therapeutics Inc Brisbane California USA

Clinical Development Vera Therapeutics Inc Brisbane California USA

Department of Cardiovascular Sciences College of Medicine Biological Sciences and Psychology University of Leicester Leicester UK

Department of Nephrology 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic

Department of Nephrology and Clinical Immunology Rheinisch Westfälische Technische Hochschule Aachen University Hospital Aachen Germany

Department of Nephrology AZ Delta Roeselare Belgium

Department of Nephrology Faculty of Medicine Kocaeli University Kocaeli Turkey

Division of Nephrology Department of Medicine Stanford University Stanford California USA

Division of Nephrology Department of Medicine The University of British Columbia Vancouver Canada

Hallym University Sacred Heart Hospital Anyang Korea

Medical Vera Therapeutics Inc Brisbane California USA

The George Institute for Global Health India New Delhi India; Faculty of Medicine School of Public Health Imperial College London UK; Prasanna School of Public Health Manipal Academy of Higher Education Manipal India

Western Nephrology Arvada Colorado USA

Westmead Clinical School The University of Sydney Sydney Australia

References provided by Crossref.org

Long-Term Results from an Open-Label Extension Study of Atacicept for the Treatment of IgA Nephropathy

Advances in Multitarget Therapeutic Approaches for Immune-Mediated Glomerular Diseases