DZP Improves Disease Activity and Reduces Corticosteroid Use in SLE

Megan Clowse, MD, MPH

Credit: Duke University School of Medicine

Dapirolizumab Pegol (DZP) was superior to placebo in achieving responses in patients with systemic lupus erythematosus (SLE) and permitted corticosteroid tapering.¹

These findings, from the phase 3 PHOENYCS GO trial (NCT04294667), were presented by Megan Clowse, MD, MPH, Associate Professor of Medicine, Associate Professor in Obstetrics and Gynecology, and Associate Professor in Population Health Sciences, and Chief of the Division of Rheumatology and Immunology, Duke University School of Medicine, at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC.

“We know that patients with lupus have a really high unmet need. They often live with really chronic and flaring inflammatory symptoms, and they also often have long term consequences of needing medications like high dose corticosteroids. So, we really focused on addressing those 2 needs in this phase 3 trial,” Clowse told HCPLive® during the meeting.

The 48-week, randomized, placebo-controlled PHOENYCS GO trial included with moderate-to-severe SLE with persistently active or frequently flaring/relapsing-remitting disease activity despite stable standard of care (SOC) medication (antimalarials, corticosteroids, and/or immunosuppressants). The full analysis set included 208 patients (90.1% of those enrolled) receiving 24 mg/kg of DZP² with SOC every 4 weeks and 107 patients (84.3% of those enrolled) receiving placebo with SOC every 4 weeks. Participants could enter an open-label extension or complete a 6-wk safety follow-up. The trial’s primary endpoint was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response at week 48 and secondary endpoints included SLE Responder Index (SRI)-4 response at week 48 and prevention of severe BILAG flares through week 48.¹

The DZP group had a mean age of 43.5 years (standard deviation [SD], 12.3) and the placebo group had a mean age of 41.5 years (SD, 12.4). Both groups were predominantly female (DZP, 92.8%; placebo, 93.5%) and around half (DZP, 50.5%; placebo, 47.7%) had over 7.5 mg/day of systemic corticosteroid use.¹

The trial met its primary endpoint, with 49.5% (n = 103) of the DZP group and 34.6% (n = 37) of the placebo group achieving BICLA response at week (P = .0110; difference, 14.6% [95% CI, 3.3-25.8]). Similarly, 60.1% (n = 125) of the DZP group and 41.1% (n = 44) of the placebo group achieved SRI-4 response at week 48 (nominal P = .0014; difference, 18.8% [95% CI, 7.3-30.3]).¹

Severe BILAG flares occurred in 11.6% of the DZP group and 23.4% of the placebo group through week 4 (nominal P = .0257; difference, 11.5% [95% CI, 1.4-21.6]). Patients receiving over 7.5 mg/day of corticosteroids prednisone equivalent started tapering no later than week 8 to reach at most 7.5 mg/day as per protocol. In these patients, 72.4% (n = 76) of the DZP group and 52.9% (n = 27) of the placebo group reduced their dose to at most 7.5 mg/day at week 48 (nominal P = .0404; difference, 17.1%).¹

In terms of safety, investigators found that more of the DZP group (82.6% vs 75.0%) had at least treatment-emergent adverse event (TEAE) but less had serious TEAEs (9.9% vs 14.8%). Opportunistic infections were reported in 2.8% of the DZP group and 0.9% of the placebo group. There was 1 thromboembolic TEAE (myocardial infarction) and 1 death (due to gangrene-related sepsis) in patients with predisposing medical history in the DZP group.¹

“People were able to taper steroids and their lupus symptoms got significantly better through the study. We really addressed both of those needs, that people need to be on less steroids and feel better, and we managed to do that really nicely,” Clowse said.

REFERENCES

1. Clowse M, Isenberg D, Merrill J, et al. Dapirolizumab Pegol Demonstrated Significant Improvement in Systemic Lupus Erythematosus Disease Activity: Efficacy and Safety Results of a Phase 3 Trial. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract L16

2. Powlesland AS, Cutcutache I, Skelton A, et al. POS0297 Dapirolizumab Pegol Impacts Important Immunologic Pathways in Systemic Lupus Erythematosus: Pharmacodynamic Analysis of T Cell and Antigen Presenting Cell Pathways From a Phase 2b Trial. Annals Rheumatic Diseases 2024;83:261.