REGENCY phase III trial: Obinutuzumab for lupus nephritis

There remains an unmet need for improved short- and long-term outcomes in patients with LN. Obinutuzumab, an anti-CD20 monoclonal antibody approved for the treatment of CLL and FL, demonstrated improved complete renal response (CRR) and delayed time to LN flare in a phase II study.¹

The phase III REGENCY trial (NCT04221477) was initiated to evaluate the efficacy and safety of obinutuzumab in adults with biopsy-confirmed active LN (Class III or IV, with or without Class V disease).¹ 271 patients were randomized 1:1 to receive obinutuzumab (1,000 mg on Day 1 and at Weeks 2, 24, 26, and 52, with or without an additional dose at Week 50) or placebo in addition to standard therapy (MMF + prednisone). Results were published by Furie et al.¹ in the New England Journal of Medicine. 

Key learnings

The primary endpoint of CRR at Week 76 was achieved by 46.4% of the obinutuzumab group vs 33.1% in the placebo group (p = 0.02). Subgroup analysis suggests CRR at Week 76 was mostly consistent across patient subgroups, regardless of disease class.

A higher proportion of patients in the obinutuzumab group vs placebo group achieved CRR with ≤7.5 mg/day prednisone (42.7% vs 30.9%; p = 0.04), suggesting potential for reducing long-term glucocorticoid exposure.

Obinutuzumab was associated with higher rates of SAEs (32.4% vs 18.2%), particularly infections, including COVID-19-related complications. However, the proportion of patients with AEs was similar between groups.

These findings support B cell depletion as a promising strategy in LN management. The addition of obinutuzumab to standard therapy improves CRR and may offer a viable option for patients with high disease activity.