Phase III MAJESTY Trial Shows Obinutuzumab Superior to Tacrolimus in Primary Membranous Nephropathy

Findings from the Phase III MAJESTY trial (NCT04629248) demonstrate that adult patients with primary membranous nephropathy administered Gazyva/Gazyvaro (obinutuzumab; Roche) achieved statistically significant and clinically meaningful improvements in complete remission at two years compared with tacrolimus. The findings position the anti-CD20 monoclonal antibody as a potential new therapeutic option in a disease area lacking in currently approved treatments.^1,2

“These results demonstrate that Gazyva/Gazyvaro may help more people with primary membranous nephropathy achieve complete remission, maintain kidney function for longer and delay or potentially prevent the onset of life-threatening complications,” said Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development. “If approved, Gazyva/Gazyvaro would be the first therapy specifically indicated for people with primary membranous nephropathy, where there are limited treatment options.”¹

Primary membranous nephropathy overview and statistics

Primary membranous nephropathy is a chronic autoimmune kidney disorder characterized by immune-mediated injury to the glomeruli, leading to proteinuria and progressive decline in renal function. The condition affects an estimated 96,000 individuals in the United States and nearly 88,000 in the European Union.

Over a 10-year period, up to 30% of patients may progress to kidney failure, requiring dialysis or transplantation and facing elevated risks of morbidity and mortality.

Gazyva/Gazyvaro mechanism of action and approved indications

• Gazyva/Gazyvaro is a type II anti-CD20 humanized monoclonal antibody engineered to enhance direct B-cell depletion and antibody-dependent cellular cytotoxicity.
• By targeting CD20-positive B cells implicated in autoimmune activity, the therapy is designed to address a root driver of immune-mediated kidney injury.
• Gazyva/Gazyvaro is currently approved in more than 100 countries for the treatment of lymphoma, including in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia; in combination with chemotherapy followed by Gazyva monotherapy in patients with stage II bulky, III, or IV follicular lymphoma (FL); and combined with (Bendeka) bendamustine followed by Gazyva monotherapy for FL in adults who did not respond to a rituximab-containing regimen, or whose FL returned.

MAJESTY trial design

• The randomized, open-label, multicenter MAJESTY trial evaluated the efficacy and safety of Gazyva/Gazyvaro compared with tacrolimus in adults with primary membranous nephropathy.
• A total of 142 participants were randomly 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.
• Key secondary endpoints included overall remission at week 104 and complete remission at week 76.

MAJESTY trial efficacy results

At two years, a significantly higher proportion of patients receiving Gazyva/Gazyvaro achieved complete remission compared with those treated with tacrolimus, meeting the study’s primary endpoint. Analyses of key secondary endpoints also demonstrated statistically significant and clinically meaningful advantages for Gazyva/Gazyvaro, including higher rates of overall remission at week 104 and improved complete remission rates at week 76 versus tacrolimus.

Full data from MAJESTY are expected to be presented at an upcoming scientific meeting and submitted to regulatory authorities, including the FDA and the European Medicines Agency.

Gazyva/Gazyvaro safety profile

The safety findings were consistent with the established profile of Gazyva/Gazyvaro. No new safety signals were identified during the study. MAJESTY represents 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.

Collectively, these studies further define the potential role of B-cell–targeted therapy across a range of autoimmune kidney and systemic conditions.

References

1. Roche announces positive phase III MAJESTY results for Gazyva/Gazyvaro in primary membranous nephropathy. News release. Roche. Accessed February 16, 2026.

2. A Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy (MAJESTY). Updated January 7, 2026. Accessed February 16, 2026. https://clinicaltrials.gov/study/NCT04629248.