Dapirolizumab pegol increases BICLA response rate by 14.6% over placebo in moderate-to-severe SLETrial shows dapirolizumab pegol improves symptoms for lupus patients

BACKGROUND: Dapirolizumab pegol is a novel CD40 ligand inhibitor. In this phase 3 trial, we aimed to evaluate the efficacy and safety of dapirolizumab pegol in patients with systemic lupus erythematosus (SLE). METHODS: PHOENYCS GO was a 48-week, randomised, double-blind, placebo-controlled, phase 3 trial conducted in 177 centres (hospitals, private practices, and trial centres) in 25 countries. Patients aged 16 years or older with moderate-to-severe, active SLE despite standard-of-care medication were randomly assigned (2:1), via an interactive web response system, to intravenous dapirolizumab pegol 24 mg/kg or placebo every 4 weeks in addition to standard of care. Patients, investigators, and funders were blinded to treatment assignments. The primary outcome was British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 48. Efficacy analyses were conducted on a modified intention-to-treat population. Safety analyses included all randomly assigned patients who received at least one study medication dose. This trial is registered with ClinicalTrials.gov (NCT04294667) and is completed. FINDINGS: Between Aug 12, 2020, and June 8, 2023, 643 patients were screened and 321 patients were randomly assigned to dapirolizumab pegol (n=213) or placebo (n=108) plus standard of care. All randomly assigned patients received at least one dose of study medication. Six patients were excluded due to non-compliance of one site with Good Clinical Practice guidelines; therefore, the full-analysis set included 315 patients (293 female, 22 male). A significantly greater proportion of patients receiving dapirolizumab pegol (50% [103/208]) versus placebo (35% [37/107]) had BICLA response at week 48 (p=0·011; difference 14·6; 95% CI 3·3-25·8). Treatment-emergent adverse events occurred in 83% (176/213) of patients receiving dapirolizumab pegol versus 75% (81/108) receiving placebo. Serious treatment-emergent adverse events occurred in 10% (21/213) of patients receiving dapirolizumab pegol versus 15% (16/108) receiving placebo. Hypersensitivity reactions during infusion occurred in 3% (6/213) of patients receiving dapirolizumab pegol. Serious infections occurred in 4% (8/213) and 6% (6/108) of patients receiving dapirolizumab pegol and placebo, respectively. One thromboembolic event (myocardial infarction) occurred in one patient in the dapirolizumab pegol group and one death (gangrene-related sepsis) occurred in another patient in the dapirolizumab pegol group. INTERPRETATION: Dapirolizumab pegol was associated with significant improvement in disease activity in patients with SLE. These findings support the further investigation of dapirolizumab pegol as a treatment option for SLE. FUNDING: UCB and Biogen.