DARALUP phase II trial: Daratumumab in moderate-to-severe SLE

Results from the single-arm, open-label, phase II DARALUP study (NCT04810754), evaluating daratumumab, an anti‑CD38 monoclonal antibody, in 10 patients with moderate-to-severe systemic lupus erythematosus (SLE) after an inadequate response to ≥2 prior immunosuppressive or immunomodulatory therapies, were published in Nature Communications by Ostendorf et al. The primary endpoint was reduction in anti-double‑stranded DNA (dsDNA) antibody levels at Week 12. Secondary endpoints included efficacy, safety, and immunologic changes. 

Key data: Anti-dsDNA antibody levels reduced by a median difference of −109.6 IU/mL (95% confidence interval [CI], −274.5 to −38.1) at Week 12 and a median difference of −123.0 IU/mL (95% CI, −236.4 to −34.2) at Week 36. A median reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‑2K) score of −8 was observed at Week 12 and −9 at Week 36. The Systemic Lupus Erythematosus Responder Index-4 (SRI‑4) response rate was 100% at Week 12 and 70% at Week 36. Treatment-emergent adverse events (TEAEs) occurred in 90% of patients and most frequently included infections (80%), gastrointestinal events (60%), and hypogammaglobulinemia (50%). There were no severe adverse events (SAEs). 

Key learning: Daratumumab demonstrated rapid and sustained efficacy in patients with SLE and an inadequate response to immunosuppressive or immunomodulatory therapies, supporting its potential as an induction therapy. Larger, controlled trials are warranted to confirm findings from this study.