Obinutuzumab Achieves 37% Complete Remission vs 6% for Tacrolimus in Phase 3 PMN Trial
Phase 3 MAJESTY trial results show obinutuzumab led to 37% complete remission at 2 years vs 6% with tacrolimus in primary membranous nephropathy, with comparable safety. Genentech announced the positive data in February 2026, positioning obinutuzumab as a potential first approved therapy for PMN.
The phase 3 MAJESTY trial demonstrated that obinutuzumab (Gazyva) achieved a significantly higher rate of complete remission at 2 years compared to tacrolimus in patients with primary membranous nephropathy (PMN). At 104 weeks, 37% of obinutuzumab-treated patients achieved complete remission versus only 6% of those receiving tacrolimus, an adjusted difference of 31 percentage points (P<0.001). These findings were published in the New England Journal of Medicine.
The randomized, open-label, multicenter study enrolled 142 adults with PMN, who were assigned in a 1:1 ratio to receive either intravenous obinutuzumab or oral tacrolimus. The primary endpoint was complete remission at week 104, defined as a low urinary protein-to-creatinine ratio and stable kidney function. Obinutuzumab also showed statistically significant and clinically meaningful improvements in key secondary endpoints, including overall remission (complete or partial) at week 104 and complete remission at week 76.
Safety profiles were comparable between the two groups, with no new safety signals identified. Serious adverse events occurred in 22% of the obinutuzumab group and 19% of the tacrolimus group, and infection rates were similar. However, more patients in the tacrolimus group discontinued treatment due to adverse events. These results align with the established safety profile of obinutuzumab.
Approximately 30–40% of PMN patients with severe proteinuria progress to end-stage renal disease or experience significant irreversible kidney failure within 10 years of diagnosis. Failure to achieve remission has been associated with increased rates of need for renal replacement therapy and death.
Genentech announced the positive 2-year phase 3 results on February 16, 2026. Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody that induces direct B-cell death and antibody-dependent cellular cytotoxicity, could become the first approved treatment specifically indicated for PMN. The chief medical officer and head of Global Product Development stated that these results suggest obinutuzumab may help patients achieve complete remission, maintain kidney function, and delay or prevent life-threatening complications.