FDA Reviews Gazyva for Lupus Nephritis

The filing acceptance is based on positive results from the phase III REGENCY study, which showed improved complete renal response (CRR) with Gazyva/Gazyvaro plus standard therapy compared with standard therapy alone. The FDA is expected to make a decision on approval by October 2025.

The phase III REGENCY results, which were simultaneously presented at the World Congress of Nephrology (WCN) and published in the New England Journal of Medicine in February 2025, showed that nearly half of patients on Gazyva/Gazyvaro plus standard therapy achieved a CRR, with a statistically significant and clinically meaningful improvement, compared with standard treatment alone. This was accompanied by clinically meaningful improvements in complement levels and reductions in anti-dsDNA, markers of disease activity and inflammation. A pre-specified subgroup analysis showed consistent CRR benefit across patient subgroups, highlighting treatment potential for a broad patient population with a high unmet need. 

The REGENCY study met its primary endpoint; nearly half of patients on Gazyva/Gazyvaro plus standard therapy achieved a complete renal response (CRR), with a statistically significant and clinically meaningful improvement, compared to standard treatment alone. In the study, 46.4% of people treated with Gazyva/Gazyvaro plus standard therapy (mycophenolate mofetil and glucocorticoids) achieved CRR at 76 weeks compared with 33.1% of people treated with standard therapy alone (adjusted difference 13.4%, 95% CI, 2.0%-24.8%; P=0.0232). Two key secondary endpoints showed statistically significant and clinically meaningful benefit with Gazyva/Gazyvaro – the endpoint achieving CRR with a successful reduction of corticosteroid use and an improvement in proteinuric response (both at 76 weeks). Other secondary endpoints (mean change in estimated glomerular filtration rate at 76 weeks, overall renal response at 50 weeks) were not statistically significant, however a numerical difference in favour of Gazyva/Gazyvaro was observed. Statistically, significance for death and renal-related events through week 76 cannot be claimed due to the hierarchical design specified in the statistical analysis plan. Gazyva/Gazyvaro’s safety profile was consistent with the well-characterised profile observed in its haematology-oncology indications.

REGENCY [NCT04221477] is a phase III, randomised, double-blind, placebo-controlled, multicentre study investigating the efficacy and safety of Gazyva/Gazyvaro (obinutuzumab) plus standard therapy (mycophenolate mofetil and glucocorticoids) in people with active/chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative Class III or IV lupus nephritis, with or without Class V. The study enrolled 271 people, who were randomised 1:1 to receive Gazyva/Gazyvaro plus standard therapy or placebo plus standard therapy. REGENCY was designed based on robust phase II data and conducted during the COVID-19 pandemic. The study population was representative of the real-world population of people with lupus nephritis. 

Data from the phase III REGENCY study are also being used for a filing submission with the EMA

“In people with lupus nephritis, Gazyva/Gazyvaro demonstrated a complete renal response benefit, a meaningful clinical outcome linked to preservation of kidney function, and slowing or prevention of end-stage kidney disease,” said Dr. Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. “The FDA’s sBLA acceptance for Gazyva/Gazyvaro recognises the need to provide a more effective treatment option for people living with this devastating disease.”

“Lupus nephritis is a debilitating and potentially life-threatening condition that can lead to kidney failure and require dialysis or transplantation,” said Louise Vetter, President and Chief Executive Officer, Lupus Foundation of America. “Given the relatively young age of onset, people with lupus nephritis experience more years of disease-related complications and decreased quality of life due to the significant burden of this illness. We are hopeful for a new treatment option that can effectively reduce these risks and improve the health of all people affected by this disease.”

See citation-  Furie RA, et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N Engl J Med   2025 doi: 10.1056/NEJMoa2410965. Online ahead of print.