IMPROVEMENTS OBSERVED IN SKIN AND JOINT MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS WITH DAPIROLIZUMAB PEGOL TREATMENT: RESULTS FROM A PHASE 3 TRIAL

O009 / #367 Topic: AS24 - SLE-Treatment ABSTRACT CONCURRENT SESSION 01: FINDINGS FROM LUPUS CLINICAL TRIALS 22-05-2025 1:40 PM - 2:40 PM Background/Purpose Dapirolizumab pegol (DZP) is a novel, polyethylene glycol (PEG)-conjugated antigen-binding (Fab’) fragment, lacking an Fc domain, that inhibits CD40L signaling. In the phase 3 PHOENYCS GO trial ( NCT04294667 ) in patients with systemic lupus erythematosus (SLE), DZP resulted in improvements in different global disease activity endpoints at Week 48 vs placebo (PBO), and was generally well tolerated.[1] Here, we report the impact of DZP on SLE skin and joint manifestations in patients in the PHOENYCS GO trial. Methods PHOENYCS GO was a 48-week, randomized, double-blind, PBO-controlled trial. Patients aged ≥ 16 years with moderate-to-severe, active SLE characterized by persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medication (antimalarials, corticosteroids, and/or immunosuppressants) were included. Patients were randomized 2:1 to intravenous DZP 24 mg/kg plus SOC medication (DZP+SOC) or PBO+SOC every 4 weeks. Cutaneous Lupus Disease Area and Severity Index (CLASI) and tender/swollen joint counts (TJC/SJC) were recorded at baseline and Weeks 4, 8, 12, 24, 36, and 48. The proportion of patients achieving meaningful improvement in CLASI Activity (CLASI-A) Score (≥ 50% improvement) in all patients and those with high CLASI-A score (≥ 8) at baseline, and the proportion with a meaningful decrease in TJC/SJC (≥ 50% decrease) are reported. Difference in proportion responding between DZP+SOC and PBO+SOC, 95% CIs, and p values were estimated and tested using the Cochran-Mantel-Haenszel (CMH) risk difference estimate controlling for stratification factors. Analyses were performed on the full analysis set. Results At baseline, mean (SD) CLASI-A score was similar between patients receiving DZP+SOC (8.0 [5.7]; n = 208) and PBO+SOC (7.8 [6.8]; n = 107). Overall, 97.1% (202/208) receiving DZP+SOC and 93.5% (100/107) receiving PBO+SOC had CLASI-A score > 0 at baseline. Additionally, 45.2% (94/208) and 39.3% (42/107) receiving DZP+SOC and PBO+SOC had CLASI-A score ≥ 8 at baseline. Of all patients, 57.2% (119/208) vs 39.3% (42/107) receiving DZP+SOC vs PBO+SOC achieved ≥ 50% improvement in CLASI-A score at Week 48 (nominal p = 0.0022; difference 17.7%). Among those with CLASI-A score ≥ 8 at baseline, 57.4% (54/94) vs 38.1% (16/42) receiving DZP+SOC vs PBO+SOC achieved ≥ 50% improvement at Week 48 (nominal p = 0.0495; difference 18.2%; achievement over time is shown in Figure 1). At baseline, mean (SD) TJC was 11.7 (6.7) and 11.8 (7.5), and SJC was 7.9 (5.2) and 7.2 (5.7), in patients receiving DZP+SOC (n = 208) and PBO+SOC (n = 107), respectively. The mean (SD) number of joints which were tender and swollen (T&SJC) at baseline was 7.4 (5.0) and 6.8 (5.6) in patients receiving DZP+SOC and PBO+SOC. After 48 weeks, 65.9% (137/208) vs 50.5% (54/107) of all patients receiving DZP+SOC vs PBO+SOC achieved ≥ 50% decrease in T&SJC (nominal p = 0.0089; difference 15.2%; achievement over time is shown in Figure 2). Similar results at Week 48 were achieved for TJC only (63.5% vs 44.9%; nominal p = 0.0014; difference 18.4%) and SJC only (65.4% vs 49.5%; nominal p = 0.0078; difference 15.6%). Figure 1. Achievement of ≥ 50% improvement in CLASI-A Score over time in patients with CLASI-A Score ≥ 8 at baseline (NRI) Figure 2. Achievement of ≥ 50% decrease in T&SJC over time in all patients (NRI) Conclusions Beyond the previously reported significant improvement in overall disease activity,[1] treatment with DZP+SOC resulted in meaningful improvements in both skin and joint manifestations in patients with SLE. References: [1.] Clowse M. Arthritis Rheumatol 2024;76 (suppl 9). Acknowledgments: This study was funded by UCB and Biogen. Medical writing support provided by Costello Medical and funded by UCB and Biogen.

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