FDA approves Obinutuzumab (Gazyva) for Primary Membranous Nephropathy

The US Food and Drug Administration (FDA) has approved obinutuzumab (Gazyva) to induce remission of proteinuria in adults with primary membranous nephropathy (PMN) at risk of disease progression, making it the first drug approved specifically for this condition.¹

Approval was based on the phase 3 MAJESTY trial, in which complete remission at week 104 occurred in 26 of 71 patients (37%) receiving obinutuzumab and 4 of 70 patients (6%) receiving tacrolimus (adjusted difference, 31 percentage points; 95% CI, 18–44; P < .001).² Obinutuzumab also showed significant treatment effects on complete or partial remission at week 104 and complete remission at week 76.² The FDA reported complete remission rates of 36% and 6%, respectively.¹

Obinutuzumab, a type II anti-CD20 monoclonal antibody, was previously approved for certain hematologic cancers, active lupus nephritis, and childhood-onset idiopathic nephrotic syndrome.^1,4 The FDA granted the application Breakthrough Therapy, Orphan Drug, and Priority Review designations.¹

MAJESTY trial design and obinutuzumab efficacy in PMN

MAJESTY was a phase 3, randomized, open-label, multicenter trial assigning 142 adults with PMN 1:1 to intravenous obinutuzumab or oral tacrolimus, an off-label comparator, over 104 weeks.^1,2 The primary end point was complete remission at week 104, defined as a urinary protein-to-creatinine ratio of 0.3 or lower with a stable estimated glomerular filtration rate (eGFR).² Key secondary end points were evaluated with fixed-sequence hierarchical testing.²

The hierarchy included complete or partial remission at week 104, complete remission at week 76, a sustained eGFR reduction of at least 30%, duration of complete remission, and change in fatigue scores.² The analysis of sustained eGFR reduction did not show a significant treatment effect, so the remaining end points were not formally tested for significance.² The results were presented at the European Renal Association Congress in June 2026 and published in the New England Journal of Medicine.^2,3

Tacrolimus, a calcineurin inhibitor, is used off-label as an immunosuppressive treatment for PMN, according to the FDA.¹

Obinutuzumab safety profile and boxed warning in PMN

Adverse events of grade 3 or higher occurred in 22% of patients receiving obinutuzumab and 19% receiving tacrolimus, and serious adverse events occurred in 17% and 14%, respectively.² Infection rates were 61 and 57 per 100 patient-years, with serious infections at 3 and 4 per 100 patient-years.² One patient in each group died during escape therapy.²

Genentech described the MAJESTY safety findings as consistent with the established safety profile of obinutuzumab, with no new safety signals identified.³

Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia.² According to the FDA, the most common adverse effects in MAJESTY were infusion-related reactions and upper respiratory tract infection.¹ The prescribing information carries a boxed warning for hepatitis B virus reactivation and progressive multifocal leukoencephalopathy.¹

No therapies were previously approved by the FDA or the European Medicines Agency for PMN, and up to 30% of untreated patients progress to kidney failure over 10 years, according to Genentech.³ Genentech said MAJESTY data were also being submitted to other health authorities, including the European Medicines Agency.³

The FDA granted obinutuzumab Breakthrough Therapy Designation for PMN in April 2026 and accepted the supplemental Biologics License Application for priority review in July 2026.³

References

1. US Food and Drug Administration. FDA approves first drug to treat adults with primary membranous nephropathy. Published November 13, 2026. Accessed November 14, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-drug-treat-adults-primary-membranous-nephropathy

2. Fervenza FC, Hou FF, Hao CM, et al. Obinutuzumab or tacrolimus in primary membranous nephropathy. N Engl J Med. 2026;395(10):959-971. doi:10.1056/NEJMoa2602678

3. Genentech. FDA grants priority review to Genentech’s Gazyva for adults with primary membranous nephropathy. Published July 14, 2026. Accessed November 14, 2026. https://www.gene.com/media/press-releases/15121/2026-07-14/fda-grants-priority-review-to-genentechs

4. HCPLive. FDA approves obinutuzumab (Gazyva) for idiopathic nephrotic syndrome. https://www.hcplive.com/view/fda-approves-obinutuzumab-gazyva-for-idiopathic-nephrotic-syndrome. Published September 25, 2026. Accessed November 14, 2026.