Daxdilimab in moderate-to-severe DLE: Phase II trial results

Results from a randomized, placebo-controlled, phase II trial (NCT05591222) evaluating daxdilimab in patients with moderate-to-severe discoid lupus erythematosus (DLE) were presented by Victoria P. Werth at the European Academy of Dermatology and Venereology (EADV) Congress 2026, September 30 – October 3, 2026, Vienna, AT. Patients were randomized to receive low-dose daxdilimab (n = 24), high-dose daxdilimab (n = 23), or placebo (n = 25). The primary endpoint was Cutaneous Lupus Erythematosus (CLE) Area and Severity Index-Activity (CLASI-A) at Week 24.

Key data: At Week 24, the primary endpoint was met, with both low- and high-dose daxdilimab demonstrating significant reductions in CLASI-A scores vs placebo, with least squares mean difference in change from baseline of –6.0 (90% confidence interval [CI], –8.7 to –3.2; p = 0.0005) and –5.7 (90% CI, –8.5 to –2.9; p = 0.0012), respectively; differences were significant from Week 4 in the low-dose group and from Week 8 in the high-dose group. A greater proportion of patients receiving low- and high-dose daxdilimab attained Cutaneous Lupus Activity Investigator’s Global Assessment (CLA-IGA) scores of 0/1 (both p < 0.05), ≥70% reduction from baseline in CLASI (CLASI70; both p < 0.05), and CLASI-A scores of 0–3 (both p < 0.05) at Week 24. Rates of adverse events (AEs) were similar between patients receiving low-dose daxdilimab, high-dose daxdilimab, and placebo (58.3%, 56.5%, and 60.0%, respectively). The most frequently reported treatment-emergent AEs (TEAEs) in the overall daxdilimab population were headache (10.6%), cough (6.4%), diarrhea (6.4%), and upper respiratory tract infection (URTI; 6.4%).

Key results: In this phase II trial, daxdilimab demonstrated significant improvements in disease activity vs placebo, regardless of dose level, with a well-tolerated safety profile in patients with moderate-to-severe DLE, supporting further investigation in this patient population.