ALLEGORY phase III: Obinutuzumab in patients with active SLE

Results from the phase III, double-blind, placebo-controlled ALLEGORY trial (NCT04963296), evaluating obinutuzumab in 303 adults with active systemic lupus erythematosus (SLE), were published in the New England Journal of Medicine by Furie et al. The primary endpoint was a response on the SLE Responder Index (SRI)‑4 at Week 52, which was defined by a reduction from baseline of ≥4 points in SLE Disease Activity Index 2000 (SLEDAI‑2K) score, no worsening of British Isles Lupus Assessment Group 2004 index (BILAG‑2004) and Physician’s Global Assessment (PGA) score, and no intercurrent events. Key secondary endpoints included BILAG-based Composite Lupus Assessment (BICLA) response at Week 52, sustained glucocorticoid reduction from ≥10 mg to ≤7.5 mg from Week 40 to 52, sustained SRI‑4 response from Week 40 to 52, SRI‑6 response at Week 52, and time to first BILAG-defined flare. 

Key data: At Week 52, 76.7% of patients receiving obinutuzumab demonstrated an SRI‑4 response, compared with 53.5% of patients receiving placebo (95% confidence interval [CI], 12.5–33.6; p < 0.001). A BICLA response (62.0% vs 40.2%; p < 0.001), a reduction in glucocorticoid dose between Week 40 and 52 (80.0% vs 54.1%; p < 0.001), a sustained SRI‑4 response between Week 40 and 52 (72.0% vs 46.4%; p < 0.001), and an SRI‑6 response at Week 52 (68.9% vs 38.9%; p < 0.001) were achieved in more patients in the obinutuzumab group vs the placebo group. Patients receiving obinutuzumab were also less likely to have a BILAG flare through Week 52 (33.8% vs 48.7%; p = 0.002). Adverse events (AEs) occurred more frequently in patients receiving obinutuzumab vs placebo (88.7% vs 81.5%), with Grade ≥3 AEs occurring in 16.6% and 13.9% of patients, respectively.  

Key learning: Obinutuzumab demonstrated significant improvements in global disease activity, steroid reduction, and flare prevention compared with placebo, supporting its potential as a treatment option in adults with active SLE.