REGENCY: Obinutuzumab Proves Efficacy in Lupus Nephritis

Richard Furie, MD
Credit: Northwell Health

Use of obinutuzumab (Gazya/Gazyvaro) was superior to standard of care therapy alone for achieving a complete renal response in patients with active lupus nephritis, according to results from the phase 3 REGENCY trial.

A CD20-directed cytolytic antibody indicated for the combination treatment of patients with chronic lymphocytic leukemia and follicular lymphoma dating back to 2013, results of the trial indicate 46.4% of patients using obinutuzumab achieved a complete renal response, which represents a 13.4% adjusted difference relative to standard of care therapy alone. Results also indicated use was associated with a statistically significant and clinically meaningful improvement in markers of disease activity and inflammation.^1,2

“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 Richard Furie, MD, the Marilyn and Barry Rubenstein Chair in Rheumatology and Chief of the Division of Rheumatology at Northwell Health.² “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.”

Until recently, the management of lupus nephritis represented an area of significant unmet need in medicine, but notable advances, including approvals of belimumab and voclosporin, have transformed the long-term prognosis for many. However, as the investigators of the REGENCY trial cite, a significant degree of that unmet need persists.¹

Launched in 2020 following the success of the phase 2 NOBILITY trial, the phase 3 REGENCY trial was conducted at centers in 15 countries and included 271 people, who were randomized 1:1 to receive either biannual intravenous dosing of obinutuzumab plus standard therapy or placebo plus standard therapy.¹

For inclusion in the phase 3 REGENECY trial, patients needed 18 to 75 years of age, meet the American College of Rheumatology classification criteria for systemic lupus erythematosus, and had active class III or IV lupus nephritis, with or without concomitant class V disease according to the classification of the International Society of Nephrology and the Renal Pathology Society. Investigators noted this was confirmed on kidney biopsy performed either during or within 6 months before screening.¹

Of note, patients were excluded if they had an eGFR lower than 30 mL/min/1.73m2 of body surface area or end-stage kidney disease necessitating dialysis or transplantation, evidence of active infection, receipt of anti-CD20 therapy during or within 9 months before screening, and receipt of cyclophosphamide, tacrolimus, cyclosporine, or voclosporin therapy during or within 2 months before screening. For the purpose of analysis, standard of care therapy was defined as mycophenolate mofetil and prednisone and all patients were started at randomization, if they were not already receiving it.¹

For the primary endpoint of interest, use of obinutuzumab wasd aqssociated with a statistically significant and clinically meaningful improvement in complete renal response, with 46.4% achieving complete renal response at 76 weeks compared to just 33.1% of people treated with standard therapy alone (adjusted difference, 13.4%; 95% CI, 2.0 to 24.8; P = .0232). Investigators pointed out there were no unexpected safety signals identified in the trial, but more serious adverse events, mainly infections and events related to coronavirus disease 2019, occurred among the obinutuzumab group.¹

In their release, Roche highlighted secondary endpoint analyses indicating complete renal response with prednisone taper from week 64 to week 76 was achieved in 42.7% (95% CI, 34.3 to 51.1) of patients in the obinutuzumab group compared to 30.9% (95% CI, 23.1 to 38.7) in the placebo group, with a treatment difference of 11.9% (95% CI, 0.6 to 23.2; P = .0421). Achievement of proteinuric response at week 76 (UPCR <0.8 g/g) was greater in the obinutuzumab group (55.5%; 95% CI, 47.1 to 64.0) than the placebo group (41.9%; 95% CI, 33.6 to 50.2), yielding a treatment difference of 13.7% (95% CI, 2.0 to 25.4; P = .0227).^1,2

There was no statistically significant difference in mean adjusted change in eGFR from baseline to week 76 between the obinutuzumab group and the placebo group. However, the incidence of death or renal-related events through Week 76 was significantly reduced in the obinutuzumab group (18.9%; 95% CI, 12.1 to 25.6) relative to the placebo group, with a treatment difference of -16.83% (95% CI, -27.4 to -6.2; P = .0026).¹

“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 [obinutuzumab] compared to standard treatment alone,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development.² “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.”

References:

Furie RA, Rovin BH, Garg JP. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. New England Journal of Medicine. Published online February 7, 2025. doi:10.1056/NEJMoa2410965

Roche. New England Journal of Medicine publishes new data for Roche’s Gazyva/Gazyvaro which shows superiority over standard therapy in people with active lupus nephritis. Roche. February 7, 2025. Accessed February 7, 2025. https://www.roche.com/media/releases/med-cor-2025-02-07.