UCB and Biogen announced positive topline results from the Phase 3 PHOENYCS GO study, evaluating dapirolizumab pegol (DZP) in patients with moderate-to-severe systemic lupus erythematosus (SLE). The study demonstrated significant clinical improvement in disease activity, offering hope for a new treatment option for this challenging autoimmune condition. The findings were presented at ACR Convergence 2024, the American College of Rheumatology’s annual meeting.
Primary Endpoint Achieved
The PHOENYCS GO study (n=321) administered DZP intravenously every four weeks. The primary endpoint, improvement in disease activity measured by the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) at 48 weeks, showed a statistically significant 14.6% higher response rate (49.5%) in the DZP plus standard of care (SOC) group compared to SOC alone (34.6%; 95% CI: 3.3, 25.8; p=0.0110).
Secondary Endpoints Show Clinical Benefit
While the first secondary endpoint, BICLA response at Week 24, did not reach statistical significance (p=0.1776), subsequent analyses of additional secondary endpoints revealed notable clinical improvements in the DZP group. These included:
- A 17.1% greater proportion of participants reducing their corticosteroid dose from >7.5 mg/day prednisone equivalent at baseline to ≤7.5 mg/day at Week 48 (72.4% vs. 52.9%; difference [95% CI]: 17.1% [0.7, 33.4]; nominal p=0.0404).
- An 18.8% higher SRI-4 response rate at Week 48 (95% CI: 7.3, 30.3; nominal p=0.0014) in the DZP plus SOC group (60.1%) versus the SOC alone group (41.1%).
- A 1.8-fold greater decrease from baseline in SLEDAI-2K in the DZP plus SOC group compared to SOC alone at Week 48 (-6.1 vs –4.2; difference [95% CI]: -1.8 [-2.7, -0.9]; nominal p=0.0001).
- A 20.9% greater proportion of participants in the DZP group achieving Lupus Low Disease Activity State (LLDAS) at Week 48 compared to SOC alone (40.9% vs. 19.6%; difference [95% CI]: 20.9% [10.7, 31.2]; nominal p<0.001).
- Participants receiving DZP plus SOC experienced 50% fewer severe BILAG flares through Week 48 (95% CI: 1.4, 21.6; nominal p=0.0257) compared to SOC alone (11.6% vs. 23.4%).
Safety Profile
The safety profile of dapirolizumab pegol was generally favorable, consistent with previous studies. A higher proportion of patients receiving DZP plus SOC had treatment-emergent adverse events (TEAEs) compared to SOC alone (82.6% vs. 75.0%). Serious TEAEs occurred in 9.9% of participants receiving DZP plus SOC compared to 14.8% in those receiving SOC alone. Opportunistic infections were reported in 2.8% of participants receiving DZP plus SOC compared to 0.9% of those receiving SOC alone. Discontinuation of treatment due to TEAEs occurred in 4.7% of participants receiving DZP plus SOC and 3.7% receiving SOC alone.
Implications for SLE Treatment
These results suggest that dapirolizumab pegol has the potential to provide clinically meaningful improvements across multiple disease domains for individuals living with SLE. “There remains a significant unmet need for additional treatment options for people living with systemic lupus erythematosus and the results we observed in PHOENYCS GO suggest dapirolizumab pegol has the potential to be impactful for this chronic and debilitating autoimmune disease,” said Megan E.B Clowse, M.D., principal investigator of the study and Associate Professor of Medicine, Chief of the Division of Rheumatology and Immunology at Duke University School of Medicine.
UCB and Biogen will initiate a second Phase 3 trial of dapirolizumab pegol, PHOENYCS FLY (NCT06617325), to further evaluate its efficacy and safety.
