Abstract / Summary
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). 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. 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. 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. UCB and Biogen.
Primary Source
Lancet (London, England)
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