The U.S. Food and Drug Administration announced Friday, Nov. 13, that it approved Gazyva (obinutuzumab) to induce remission of proteinuria in adults with primary membranous nephropathy who are at risk of disease progression, calling it the first drug approved to treat the condition. The pivotal MAJESTY trial beat tacrolimus, an off-label calcineurin inhibitor, 36% to 6% on complete remission at week 104, but it never tested Gazyva against rituximab, an antibody the 2021 KDIGO guideline already indicates for moderate- to high-risk disease, and kidney function did not differ between the two arms over two years.

Membranous nephropathy is an autoimmune kidney disease in which antibodies attack the glomeruli, the kidney’s filtering units, and protein spills into the urine. Genentech, a member of the Roche Group, estimates U.S. incidence at 1.2 per 100,000 people per year and says up to 30% of untreated patients develop kidney failure over 10 years. Estimates of how many Americans live with the disease differ by nearly a factor of three: Genentech cites more than 96,000, while Biogen, which is developing a rival antibody, cites about 36,000 patients.

For patients and nephrologists, the approval delivers the first on-label option, but the trial design leaves open the question that matters most in clinics: whether Gazyva outperforms rituximab, the off-label B-cell antibody that guidelines already recommend for higher-risk patients after a 2019 trial. The sections below separate what the label covers, what the data show, how the drug differs from rituximab and what the safety record includes.

FDA Label Covers Proteinuria Remission, and Kidney Function Did Not Differ Between Arms

The approved indication is to induce remission of proteinuria, meaning protein in the urine, in adults with primary membranous nephropathy at risk of progression. The FDA defined complete remission as a urine protein-to-creatinine ratio of 0.3 g/g or lower with a stable estimated glomerular filtration rate (eGFR), without rescue therapy, treatment failure or early discontinuation. The FDA reported 36% complete remission on Gazyva versus 6% on tacrolimus, while HCPLive’s summary of the New England Journal of Medicine paper reports 26 of 71 patients (37%) versus 4 of 70 (6%). The adjusted difference was 31 percentage points (95% confidence interval 18 to 44; P<.001 and="" genentech="" own="" analysis="" put="" the="" rates="" at="" rel="nofollow" href="https://www.businesswire.com/news/home/20260714394570/en/" class="external_red">36.9% versus 5.7%.

Secondary endpoints favored Gazyva too. According to NephJC’s trial summary, overall remission, complete or partial, reached 51% versus 13% at week 104, and complete remission at week 76 reached 44% versus 14%. The trial’s fixed-sequence testing then hit a wall: the next endpoint, a sustained eGFR drop of more than 30%, occurred in 6% of patients in both arms, so testing stopped and later results, including duration of complete remission and fatigue scores, are descriptive only. NephJC reports no difference in kidney function between the arms, an outcome it describes as expected over two years in a group whose average starting eGFR was above 80. The label therefore rests on proteinuria remission, not on proof that Gazyva delays kidney failure within the trial’s two-year window.

Genentech’s Jay Garg, global head of nephrology and rheumatology, argues that reaching a protein level below 0.3 strongly predicts long-term kidney outcomes. That is a sponsor executive’s reading, and the trial did not test it directly.

Trial Counted Escape Therapy as Failure, and 61% of Tacrolimus Patients Needed It

MAJESTY was a randomized, open-label Phase 3 trial of 142 adults at 49 sites in 11 countries, assigned 1:1. Gazyva was given as 1,000 mg intravenous infusions on day 1, week 2, week 24 and week 26, while tacrolimus continued to week 52 and was then tapered over eight weeks. The FDA announcement did not describe dosing and referred readers to the prescribing information.

The primary analysis counted escape therapy as non-response. In the tacrolimus arm, 61% of patients met escape criteria and received obinutuzumab, versus 28% in the Gazyva arm, and tacrolimus responders relapsed often after the drug was withdrawn at 52 weeks. A sensitivity analysis using a treatment-policy approach gave a similarly wide gap, 44% versus 14%. NephJC commentator Jamie Willows wrote that the outcome was expected, because Gazyva was compared with a single 52-week tacrolimus course, and that the advantage over rituximab is modest.

The comparator matters because the 2019 MENTOR trial found rituximab noninferior to cyclosporine at 12 months and superior at 24 months. NephJC’s cross-trial comparison puts complete remission at week 104 at 37% for Gazyva in MAJESTY and 35% for rituximab in MENTOR, with lower overall remission for Gazyva (51% versus 60%) in a trial that also required stable eGFR. Cross-trial numbers cannot settle the question, and NephJC estimates that a superiority trial against rituximab would need roughly 2,500 patients. Genentech and Biogen also co-market rituximab as Rituxan in the U.S., whose patent expired in 2015 and which now competes with FDA-approved biosimilars. Genentech frames Gazyva as targeting tissue-resident B cells, which it says addresses an underlying cause of the disease.

How Does Gazyva Differ From Rituximab? Glycoengineering and Type II Binding Add Immune Killing and Direct Cell Death

Both drugs target CD20, a protein found on B cells from the pre-B stage through memory B cells, but not on plasma cells. Garg describes the logic as cutting off the source of the pathogenic antibodies by depleting the B cells that make them.

Gazyva is a humanized anti-CD20 antibody that binds a partially overlapping epitope to the one rituximab recognizes. Its producer cells are engineered to overexpress the enzymes MGAT3 and Golgi mannosidase II, which reduces fucose on the antibody and increases natural killer cell activation. Genentech describes Gazyva as a glycoengineered antibody designed for deep tissue B-cell depletion, and Garg credits its mechanism for much greater B-cell depletion than earlier anti-CD20 antibodies achieve. Rituximab is a chimeric antibody with mouse-derived sequences, and a 2020 Cedars-Sinai pilot study of 10 patients, 6 of them rituximab-refractory, reported complete remission in 4 and partial remission in 5, including one patient who had suffered infusion anaphylaxis with rituximab. That study had no control arm and was retrospective, so it signals plausibility rather than proof.

In MAJESTY, CD19-positive B-cell counts fell below 10 cells per microliter in 94% of Gazyva patients at week 52, while the share still below that threshold dropped to 14% by week 104. Garg said about three-quarters of patients cleared their autoantibody by six months, a sponsor statement that fits the logic of the mechanism but that the sources reviewed do not break down by arm.

The engineering constraint is that CD20 disappears as B cells mature into plasma cells, so anti-CD20 antibodies spare long-lived plasma cells that can persist in bone marrow for years. That gap is what plasma-cell-directed approaches, such as Biogen’s anti-CD38 antibody felzartamab, are positioned to address. Tacrolimus works differently: it binds the protein FKBP1A and the complex inhibits calcineurin.

Boxed Warnings for Hepatitis B Reactivation and PML Apply, and Two Deaths Followed Escape Therapy

The Gazyva label carries a boxed warning for hepatitis B virus reactivation and progressive multifocal leukoencephalopathy (PML), a rare and serious brain infection, and the FDA lists infusion-related reactions and upper respiratory tract infection as the most common side effects in the membranous nephropathy study. HCPLive’s summary of the New England Journal of Medicine paper reports grade 3 or higher adverse events in 22% of Gazyva patients versus 19% on tacrolimus, serious adverse events in 17% versus 14%, and infections at 61 versus 57 per 100 patient-years, with serious infections at 3 versus 4 per 100 patient-years. Infusion reactions occurred in 38% of Gazyva patients and neutropenia in 4%. Genentech said no new safety signals emerged.

NephJC flagged reporting gaps: possible subclinical hepatitis B reactivation in two patients with unclear arm assignment and prophylaxis status, no systematic reporting of adverse events during escape therapy, and two deaths during escape therapy, one in each original arm, from COVID-19 pneumonia and cardiac arrest, which the investigators judged unrelated to the drug. The open-label design may bias subjective outcomes, and two years of follow-up leaves long-term durability and safety unknown. Genentech’s safety information says patients are screened for hepatitis B before treatment and monitored during and after it.

Is Gazyva Approved for Other Kidney Diseases? Third Kidney Indication Follows Lupus Nephritis and Nephrotic Syndrome

Gazyva began as a cancer drug, with its first FDA approval for chronic lymphocytic leukemia in November 2013. The FDA approved it for active lupus nephritis in October 2025, the first anti-CD20 antibody cleared for that use. On Sept. 25, 2026, the agency approved it for idiopathic nephrotic syndrome to reduce relapse risk in children and adults aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset disease in remission. In the INShore trial of 85 patients, sustained complete remission at week 52 reached 95.5% on Gazyva versus 73.2% on mycophenolate mofetil, and Genentech calls it the first FDA-approved treatment for that disease in 70 years.

The membranous nephropathy indication carries Breakthrough Therapy, Orphan Drug and Priority Review designations. Genentech said the FDA granted Breakthrough Therapy Designation in April 2026 and Priority Review in July 2026. The company is submitting MAJESTY data to other regulators, including the European Medicines Agency, and an FDA decision on Gazyva for systemic lupus erythematosus, based on the ALLEGORY trial, is expected by December 2026. The FDA announcement did not give a U.S. price, and none appears in the sources reviewed.

Felzartamab Phase 3 Is Not Due Until 2029, and Povetacicept Holds Fast Track Status

Biogen’s PROMINENT trial is a 104-week, open-label Phase 3 study of about 180 adults comparing felzartamab with tacrolimus, with a readout expected in 2029. Felzartamab is an anti-CD38 antibody aimed at plasma cells, and earlier Phase 2 studies enrolled 31 and 24 patients. Biogen acquired the developer, Human Immunology Biosciences, in July 2024.

Vertex’s povetacicept, a dual BAFF/APRIL inhibitor, holds FDA Fast Track and Orphan designations for the disease, along with European Medicines Agency PRIME status. Vertex faces a separate November 30 FDA action date for povetacicept in IgA nephropathy, a different kidney disease.

Patients Weighing Gazyva Against Rituximab Can Ask Nephrologists Four Questions

Reference summaries note that membranous nephropathy has an unpredictable course, with roughly one-third of untreated patients reaching spontaneous remission, which is why guidelines recommend a period of observation before immunosuppression. The label’s wording, “at risk of disease progression,” puts the timing decision in the clinic.

Four questions follow from the evidence. First, has hepatitis B screening been done, given the boxed warning? Second, why Gazyva rather than rituximab, which has years of off-label use and a guideline-listed role, when no trial compared them? Third, what is the plan if proteinuria returns, since MAJESTY followed patients for only two years? Fourth, how will the insurer treat a drug that moves from off-label to on-label use for a disease where rituximab biosimilars are already approved in the U.S.? Gazyva delivers the first FDA-approved path to proteinuria remission in membranous nephropathy, but its edge over tacrolimus is proven, its edge over rituximab is not, its kidney-function benefit is unshown at two years and its safety label includes boxed warnings that call for screening.

This article is for information only and is not medical advice.

Frequently Asked Questions

Is Gazyva better than rituximab for membranous nephropathy?

No trial has answered that. MAJESTY compared Gazyva with tacrolimus, and NephJC’s informal cross-trial comparison found similar complete-remission rates for Gazyva in MAJESTY and rituximab in MENTOR (37% versus 35%).

Does Gazyva stop kidney failure in membranous nephropathy?

Not shown yet. The approval covers inducing remission of proteinuria, and kidney function did not differ between arms over two years, so the trial did not show that Gazyva delays kidney failure.

What are the main risks of Gazyva?

The boxed warning covers hepatitis B virus reactivation and PML, a rare brain infection, and common side effects in the trial were infusion-related reactions and upper respiratory infections. Infusion reactions affected 38% of Gazyva patients in the trial.

How was Gazyva given in the MAJESTY trial?

Patients received 1,000 mg infusions into a vein on day 1, week 2, week 24 and week 26. The FDA announcement did not describe the labeled regimen, so patients should rely on the prescribing information.