Dapirolizumab pegol superior to placebo, may represent a ‘novel treatment’ for lupus

WASHINGTON — The novel CD40L inhibitor dapirolizumab pegol bested placebo in multiple systemic lupus erythematosus outcomes, including disease activity and steroid tapering, at 48 weeks, according to data presented at ACR Convergence 2024.

“Dapirolizumab pegol, or DZP, has broad immunomodulatory effects,” Megan Clowse, MD, MPH, of the division of rheumatology and immunology at Duke University, told attendees. “It reduces B- and T-cell activation and downregulates interferon pathways.”

Clowse presented findings of the phase 3 PHOENYCS GO trial, 48-week, randomized, double-blind, placebo-controlled study that assessed the efficacy and safety of dapirolizumab pegol (UCB, Biogen) in patients aged 16 years and older with moderate to severe SLE.

“These patients had frequent flares despite being stable on standard-of-care medications,” Clowse said.

These medications included antimalarials, corticosteroids and immunosuppressants. The analysis included 321 patients overall, with 213 in the active therapy arm and 108 receiving placebo.

“Mandatory corticosteroid tapering was required by week 8,” Clowse said.

Median age of patients in the cohort was older than 40 years, with “about 70%” demonstrating a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 10 or higher, according to Clowse.

“Sixty percent had low completement at enrollment, and 80% were taking antimalarials at enrollment,” she said.

According to the researchers, 49.5% of patients who received dapirolizumab pegol achieved the primary endpoint — British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 48 — compared with 34.6% in the placebo group (P = .011).

“We have statistical significance for our primary endpoint,” Clowse said.

Meanwhile, BICLA rates at 24 weeks were 46.6% in the treatment group and 38.3% for placebo (P = .1776).

“We did not quite have statistical significance for [this secondary] endpoint,” Clowse said.

Corticosteroid tapering rates were 72.4% for patients treated with dapirolizumab pegol and 52.9% in the placebo group, according to Clowse.

“This is a really important finding,” she said. “We had markedly higher rates of corticosteroid tapering in patients who were on the drug compared with placebo.”

In addition, the mean change of SLEDAI-2K was –6.1 in the treatment group and –4.2 in the placebo group, according to the researchers.

“SLEDAI-2K decreased throughout the study,” Clowse said.

Meanwhile, Lupus Low Disease Activity State (LLDAS) rates were 23.6% for dapirolizumab pegol and 15.9% for placebo, according to the findings.

“For LLDAS, you can start seeing differences very early, around week 12,” Clowse said.

Safety data showed that the drug was “generally well-tolerated throughout the 48-week period,” Clowse added.

She added that serious adverse event rates were comparable in the two arms, with placebo demonstrating slightly higher rates.

“Treatment with dapirolizumab pegol, a novel CD40L inhibitor, resulted in improvement in disease activity and corticosteroid tapering in patients with SLE,” Clowse said. “We think it may represent a novel treatment for lupus.”