Gazyva Shows Superiority in Lupus

The study demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of complete renal response (CRR), showing that 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). This was accompanied by clinically meaningful improvements in complement levels and reductions in anti-dsDNA, markers of disease activity and inflammation. Data were presented at the World Congress of Nephrology (WCN) 2025 and are being shared with health authorities, including the FDA and the EMA. 

“The fact that nearly half of lupus nephritis patients achieved a complete renal response, together with clinically meaningful benefits observed consistently across subgroups, indicates superior disease control with Gazyva/Gazyvaro compared to standard treatment alone,” said Dr. Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. “Lupus nephritis disproportionately affects younger women, mostly women of colour, often leading to end-stage kidney disease. Our goal is to address this urgent need by providing a more effective treatment option.”

“The positive REGENCY study results confirmed the findings of an earlier trial that administration of obinutuzumab, a therapy which targets B cells, benefitted patients with lupus nephritis more than standard treatment alone,” said Dr. Richard Furie, the Marilyn and Barry Rubenstein Chair in Rheumatology and Chief of the Division of Rheumatology at Northwell Health, US. “It is also gratifying to see that patients who received obinutuzumab were not only more likely to achieve the desired outcome but were able to taper corticosteroids at the same time.”

Gazyva/Gazyvaro’s safety profile was consistent with the well-characterised profile observed in its haematology-oncology indications. Key secondary endpoints showed that at week 76, patients who received Gazyva/Gazyvaro plus standard therapy were more likely to achieve CRR, with a successful reduction of corticosteroid use than standard therapy alone. In addition, a higher proportion of patients showed improvement in proteinuric response when treated with Gazyva/Gazyvaro plus standard therapy versus standard therapy alone. These endpoints are important indicators for achieving better disease control in lupus nephritis. As seen in pre-specified subgroup analyses, a benefit in CRR with Gazyva/Gazyvaro over standard therapy alone was consistent across all subgroups of patients, including indicators of more active lupus nephritis, Class IV lupus nephritis, concomitant Class V disease, higher baseline proteinuria levels, and/or greater serologic activity.

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 either biannual intravenous dosing of 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. The primary endpoint was the proportion of people who achieved a complete renal response (CRR) at 76 weeks. Key secondary endpoints included the proportion of people who achieved CRR at week 76 with successful reduction of corticosteroid use (prednisone taper); the proportion who achieved proteinuric response at 76 weeks; mean change in estimated glomerular filtration rate at 76 weeks; mean change in FACIT-F at week 76; death or renal-related events through week 76 and overall renal response at 50 weeks. Safety and tolerability were also assessed.

 See citation- Furie RA, et al. Efficacy and safety of obinutuzumab in active lupus nephritis. NEJM. [Internet; cited February 2025]. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2410965.