The novel CD40L inhibitor dapirolizumab pegol significantly reduced disease activity and corticosteroid use in patients with systemic lupus erythematosus (SLE). This was the main conclusion from the phase 3 PHOENYCS GO trial. Dapirolizumab pegol was generally well tolerated and may become a novel treatment option for SLE.
Dapirolizumab pegol is a novel PEG-conjugated antigen-binding antibody fragment (Fab’) that inhibits CD40/CD40L signaling. Dr. Megan Clowse, MD, from Duke University, in North Carolina, explained that dapirolizumab pegol has a broad modulatory effect on SLE immunopathology, including reducing B- and T-cell activation and downregulating interferon pathways1.
The global, 48-week, randomized-controlled, phase 3 PHOENYCS GO trial (NCT04294667) evaluated the efficacy and safety of dapirolizumab pegol in patients with moderate-to-severe SLE. The 321 enrolled participants were aged older than 16 years of age and had SLE with persistently active or frequently flaring/relapsing-remitting disease, despite stable standard-of-care (SOC) medication. A unique feature was the mandatory corticosteroid tapering from week 8 onwards. Participants were randomly assigned 2:1 to intravenous dapirolizumab pegol 24 mg/kg or placebo every 4 weeks for 48 weeks. Everybody continued to receive SOC. The primary endpoint was the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response after 48 weeks.
Of the participants in the dapirolizumab pegol and placebo group, 85.4% and 79.6% completed 48 weeks of treatment, respectively. At that time, there was a significant difference in the primary endpoint: 49.5% and 34.6% had a BICLA response (Δ14.6%; 95% CI 3.3–25.8; P=0.0110). An important result, according to Dr. Clowse, was the markedly higher proportion of corticosteroid tapering in participants on dapirolizumab pegol, reducing their dose to less than or equal to 7.5 mg/day by week 48. This endpoint was met by 72.4% versus 52.9% of participants in the dapirolizumab pegol and placebo group, respectively (Δ17.1%; 95% CI 0.7–33.4; nominal P=0.0404).
Dapirolizumab pegol was generally well tolerated. More participants in the dapirolizumab pegol group had more than or one treatment-emergent AEs (TEAEs: 82.6% vs 75.0%), but the rate of serious TEAEs was lower (9.9% vs 14.8%). Opportunistic infections were seen in 2.8% and 0.9% of the participants, respectively.
Medical writing support was provided by Michiel Tent
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