PHOENYCS GO phase III: Dapirolizumab pegol in SLE

Results from the randomized, double-blind, placebo-controlled, phase III PHOENYCS GO trial (NCT04294667) evaluating dapirolizumab pegol, a CD40 ligand inhibitor, plus standard of care (SoC) in 315 patients with moderate-to-severe, active systemic lupus erythematosus (SLE) were published in The Lancet by Clowse et al. The primary endpoint was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response at Week 48. Key secondary endpoints included BICLA response at Week 24, prevention of severe BILAG flares through Week 48, achievement of Lupus Low Disease Activity State (LLDAS) in ≥50% of visits through Week 48, and change from baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) at Week 48. 

Key data: A significantly greater proportion of patients receiving dapirolizumab pegol achieved a BICLA response at Week 48 vs placebo (50% vs 35%; 95% confidence interval [CI], 3.3–25.8; p = 0.011). At Week 24, 47% vs 38% of patients receiving dapirolizumab pegol vs placebo achieved a BICLA response (p = 0.18). A lower proportion of patients receiving dapirolizumab pegol experienced moderate or severe BILAG flares vs placebo through Week 48 (21% vs 37%), and LLDAS was reached in ≥50% of visits through Week 48 in 24% vs 16% of patients, respectively. Greater decreases in SLEDAI-2K (least squares mean, −6.1 vs −4.2) and Physician’s Global Assessment (PGA; least squares mean, −39.6 vs −33.4) from baseline to Week 48 were seen in patients receiving dapirolizumab pegol vs placebo. Treatment-emergent adverse events (TEAEs) occurred in 83% vs 75% of patients receiving dapirolizumab pegol vs placebo. The most common TEAEs in the dapirolizumab pegol group were COVID-19, urinary tract infection (UTI), and upper respiratory tract infection (URTI). 

Key learning: Dapirolizumab pegol + SoC demonstrated statistically significantly improved disease activity vs placebo in patients with moderate-to-severe, active SLE, with an acceptable safety profile, supporting dapirolizumab pegol as a potential treatment option for this patient population. The open-label extension trial, PHOENYCS GLIDE (NCT04976322), and a second confirmatory phase III trial, PHOENYCS FLY (NCT06617325), are ongoing.