EULAR 2026: CD40L inhibitor improves lupus disease control in phase 3 trial

Clinical Takeaway: In patients with moderate-to-severe active SLE receiving standard therapy, dapirolizumab pegol increased the likelihood of achieving a clinically meaningful response at 48 weeks and may help reduce glucocorticoid exposure while maintaining disease control.

New therapies for systemic lupus erythematosus remain limited, especially those that control disease while reducing glucocorticoid exposure—an ongoing driver of long-term toxicity.

In the phase 3 PHOENYCS GO trial presented at EULAR 2026 and published in The Lancet, investigators evaluated dapirolizumab pegol, an investigational Fc-free CD40 ligand (CD40L) inhibitor, in 321 patients with moderate-to-severe active SLE despite standard-of-care treatment. Participants were randomized 2:1 to IV dapirolizumab pegol plus standard care (n=213) or placebo plus standard care (n=108) for 48 weeks.

The primary endpoint was met. At week 48, 50% of patients receiving dapirolizumab pegol achieved a BILAG-based Composite Lupus Assessment (BICLA) response compared with 35% receiving placebo (103/208 vs 37/107; p=0.011). Favorable trends were also observed across multiple secondary and exploratory measures, including SRI-4 response, disease activity scores, severe flare prevention, skin and joint outcomes, serologic markers, and fatigue. Investigators also reported evidence of a glucocorticoid-sparing effect, with more patients able to taper prednisone-equivalent doses to ≤7.5 mg/day while maintaining disease control.

Safety findings were generally consistent with previous studies. Treatment-emergent adverse events occurred in 82.6% of patients receiving dapirolizumab pegol and 75.0% receiving placebo, while serious adverse events were less common with active treatment (10.0% vs 14.8%). Discontinuations due to adverse events were infrequent in both groups (4.7% vs 3.7%).

“The publication of the PHOENYCS GO results in The Lancet reflects the importance of these data to the rheumatology community,” said lead author Megan E.B. Clowse, MD, MPH. “Given the acute need for additional treatment options for SLE, these findings are encouraging for both clinicians and patients.” A confirmatory phase 3 trial, PHOENYCS FLY, is ongoing.

Source: Clowse MEB, et al; PHOENYCS GO Study Investigators’ Group. (2026, June 6). Lancet. Efficacy and safety of the CD40 ligand inhibitor dapirolizumab pegol in systemic lupus erythematosus (PHOENYCS GO): a randomised, double-blind, placebo-controlled, phase 3 trial