Dapirolizumab pegol (DZP), a novel Fc-free anti-CD40L drug candidate, demonstrated significant clinical improvement in disease activity in patients with moderate-to-severe systemic lupus erythematosus (SLE) in the Phase 3 PHOENYCS GO study. The results, presented at the American College of Rheumatology (ACR) Convergence 2024, suggest that DZP has the potential to address the unmet need for additional treatment options for this chronic autoimmune disease.
The PHOENYCS GO study (n=321) administered DZP intravenously every four weeks. The primary endpoint, measuring improvement in disease activity using the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) at Week 48, showed a statistically significant 14.6% higher response rate in the DZP plus standard of care (SOC) group (49.5%) compared to the SOC alone group (34.6%) (95% CI: 3.3, 25.8; p=0.0110).
Secondary Endpoint Analysis
While the first secondary endpoint of BICLA response at Week 24 did not reach statistical significance (p=0.1776), subsequent analyses of additional secondary endpoints revealed clinically meaningful improvements in the DZP group. These included:
- A 17.1% greater proportion of participants in the DZP group were able to reduce 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) among study participants who received DZP plus SOC (60.1%) versus those who received SOC alone (41.1%).
- A 1.8-fold greater decrease from baseline in SLEDAI-2K in study participants receiving DZP plus SOC 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 achieved 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 had 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 and with that in study participants with SLE receiving an immunomodulator. A higher proportion of patients receiving DZP plus SOC had treatment-emergent adverse events (TEAEs) compared to SOC alone (82.6% vs. 75.0%). The proportion of participants with serious TEAEs was 9.9% in those 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 or study participation due to TEAEs occurred in 4.7% (10) of participants receiving DZP plus SOC and 3.7% (4) of participants receiving SOC alone.
Future Directions
Participants from the PHOENYCS GO study will continue to be followed in a long-term open-label study. UCB and Biogen will initiate a second Phase 3 trial of dapirolizumab pegol, PHOENYCS FLY (NCT06617325), in 2024 to further assess its efficacy and safety.
"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. "Participants receiving dapirolizumab pegol experienced reduced lupus activity while also tapering steroids, changes important to people living with the disease."
