Roche has reported positive phase III results for Gazyva®/Gazyvaro® (obinutuzumab) in adults with primary membranous nephropathy, marking a significant development in the treatment of the chronic autoimmune kidney disease.
The global phase III MAJESTY study met its primary endpoint, demonstrating that a statistically significantly higher proportion of patients treated with Gazyva/Gazyvaro achieved complete remission at two years (104 weeks) compared with those receiving tacrolimus. The results were described as both statistically significant and clinically meaningful. The safety profile of Gazyva/Gazyvaro was consistent with its established record, with no new safety signals identified.
Analysis of key secondary endpoints also showed significant benefits for Gazyva/Gazyvaro over tacrolimus, including higher rates of overall remission—defined as complete or partial remission—at week 104 and complete remission at week 76.
Primary membranous nephropathy is a chronic autoimmune disorder in which the immune system attacks the kidney’s filtering units, or glomeruli, leading to protein leakage in the urine and progressive decline in kidney function. The condition is estimated to affect nearly 88,000 people in the European Union and more than 96,000 in the United States. Despite existing treatment approaches, up to 30% of patients progress to kidney failure within 10 years, often requiring dialysis or transplantation. Achieving complete remission is considered critical to preserving kidney function and reducing the risk of life-threatening complications such as kidney failure, idiopathic nephrotic syndrome, blood clots and cardiovascular disease.
If approved for this indication, Gazyva/Gazyvaro could become the first therapy specifically indicated for primary membranous nephropathy, where treatment options remain limited. The drug is a glycoengineered, humanised Type II anti-CD20 monoclonal antibody designed to induce direct B-cell death and enhance antibody-dependent cellular cytotoxicity through a modified Fc region. By targeting CD20, a protein expressed on certain B cells, the therapy aims to achieve deep tissue B-cell depletion and address an underlying cause of autoimmune activity.
MAJESTY (NCT04629248) is a phase III, randomised, open-label, multicentre study that enrolled 142 participants, who were assigned in a 1:1 ratio to receive either Gazyva/Gazyvaro or tacrolimus. The primary endpoint was the proportion of patients achieving complete remission at week 104.
The MAJESTY findings represent the fourth positive phase III study of Gazyva/Gazyvaro in immune-mediated diseases, following REGENCY in lupus nephritis, ALLEGORY in systemic lupus erythematosus and INShore in idiopathic nephrotic syndrome. The growing evidence base supports the drug’s potential across a range of immune-mediated conditions.
Gazyva/Gazyvaro is already approved in the United States and European Union for adults with active lupus nephritis, based on results from the REGENCY and NOBILITY studies, and is being evaluated in a global phase II trial in children and adolescents with lupus nephritis. The therapy is also approved in 100 countries for various haematological cancers.
Roche stated that the MAJESTY data will be presented at an upcoming medical meeting and shared with regulatory authorities, including the US Food and Drug Administration and the European Medicines Agency.
The company has been active in kidney disease research for more than two decades and maintains an extensive immunology pipeline focused on immune-mediated and kidney-related diseases. In addition to Gazyva/Gazyvaro, Roche has more than 10 phase II and III clinical studies underway targeting high unmet needs in immune-mediated kidney disorders, as part of its broader strategy to address the growing global burden of kidney disease.
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