Roche’s Gazyva Gets Positive Results in Phase III Study for Primary Membranous Nephropathy

Recent phase III clinical data for Gazyva/Gazyvaro, also known as obinutuzumab, mark the first global phase III study in primary membranous nephropathy (PMN) to meet its primary endpoint.¹ This represents a milestone for patients with PMN as up to 30% with this chronic autoimmune condition progress to kidney failure within 10 years. The study results demonstrate how a single molecule can be successfully investigated across a spectrum of immune-mediated diseases, following positive phase III outcomes in lupus nephritis, systemic lupus erythematosus, and idiopathic nephrotic syndrome.

How Do the MAJESTY Study Results Influence the Therapeutic Landscape for Primary Membranous Nephropathy?

The MAJESTY study, a randomized, open-label trial involving 142 adults, compared the efficacy and safety of Gazyva/Gazyvaro against tacrolimus.¹ The primary endpoint focused on the percentage of patients achieving complete remission at two years, a timeframe critical for demonstrating the maintenance of kidney function. Analysis showed that significantly more individuals reached complete remission at week 104 when treated with Gazyva/Gazyvaro. Furthermore, secondary endpoints indicated statistically significant benefits in overall remission at week 104 and complete remission at week 76.

“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,” stated Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development, in a press release.¹ He added that, “If approved, Gazyva/Gazyvaro would be the first therapy specifically indicated for people with primary membranous nephropathy, where there are limited treatment options.”¹

What Are the Manufacturing and Clinical Implications of this Humanized Monoclonal Antibody’s Design?

The success of Gazyva/Gazyvaro underscores the clinical utility of its specific protein engineering.¹ It is a humanized monoclonal antibody designed with a Type II anti-CD20 region for direct B cell death and a glycoengineered Fc region to ensure higher binding affinity and increased antibody-dependent cellular cytotoxicity. This design aims for deep tissue B cell depletion, targeting the underlying cause of conditions in which the immune system attacks the filtering units of the kidney. This mechanism has already supported the drug's approval for lupus nephritis in the US and EU, as well as for various hematological cancers in more than 100 countries.

The safety data from the MAJESTY trial were consistent with the well-characterized profile of the drug, with no new safety signals identified during the study.¹ This stability in safety is essential for developers aiming to address the needs of the nearly 184,000 people affected by PNM in the US and EU. The data will be shared with FDA and EMA as part of a broader ambition to lead in the field of immunology and kidney-related diseases.

What Other Notable Developments Are Being Made at Roche?

Earlier this month, Roche scientists made strides in the reduction of disability progression in primary progressive multiple sclerosis (PPMS) with fenebrutinib.² The developments in this treatment highlight a shift toward reversible, non-covalent Bruton’s tyrosine kinase inhibitors. Unlike covalent alternatives that form permanent bonds, this molecule releases the enzyme, which may reduce off-target effects. Its selectivity, 130 times greater than other kinases, enables precise targeting of B cells and microglia. By crossing the blood-brain barrier, it addresses chronic inflammation driving disability.

In the Phase III FENtrepid study, fenebrutinib demonstrated non-inferiority to ocrelizumab.² Regarding the impact, Garraway stated in a press release that,² “Fenebrutinib represents the first potential scientific breakthrough for the PPMS community in over a decade, demonstrating a meaningful clinical benefit in reducing disability progression in a study versus the only approved treatment in PPMS.” Professor Amit Bar-Or added,² “fenebrutinib has the potential to be a high-efficacy, oral treatment option that acts directly in the brain, targeting progressive biology, and may slow disability.” This progress validates targeting microglia to treat primary progressive multiple sclerosis, or PPMS.

References

1. Roche. Roche announces positive phase III results for Gazyva/Gazyvaro in primary membranous nephropathy, marking a significant milestone in this autoimmune disease. 2026 Feb 16. Accessed 2026 Feb 16. https://www.roche.com/media/releases/med-cor-2026-02-16
2. Roche. Roche’s fenebrutinib is the first investigational medicine in over a decade that reduces disability progression in primary progressive multiple sclerosis (PPMS). 2026 Feb 7. Accessed 2026 Feb 16. https://www.roche.com/media/releases/med-cor-2026-02-07