Enpatoran Shows Promise in Treating Lupus Rash

Medscape

3 days ago

An oral therapy targeting toll-like receptors (TLR) 7 and 8 reduced disease activity in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) with active lupus rash.
METHODOLOGY:
Cohort A of the phase 2 WILLOW study included patients with CLE and patients with mild SLE and active skin manifestation for whom no approved treatments currently exist.
In the study of the oral, small molecule TLR 7/8 inhibitor enpatoran, researchers randomly assigned 100 patients, all receiving standard-of-care medications, to placebo, 25 mg enpatoran, 50 mg enpatoran, or 100 mg enpatoran twice daily for 24 weeks.
The primary endpoint was percent change in CL Disease Area and Severity Index Activity (CLASI-A) from baseline to week 16.
TAKEAWAY:
Patients taking enpatoran all had clinically meaningful reductions to CLASI-A at week 16, with reductions of 74.6% for the group taking 25 mg twice daily, 59.8% for 50 mg twice daily, 68.5% for 100 mg twice daily, and 41.2% for placebo.
A total of 87% of patients taking 25 mg twice daily achieved ≥ 50% reduction in CLASI-A by week 24 compared with 72% for 50 mg twice daily, 73.1% for 100 mg twice daily, and 30.8% for placebo.
All patients on enpatoran also had reduced interferon gene signatures by week 2 compared with placebo, and this effect was continued through week 24.
Enpatoran was well-tolerated with no new safety signals from previous clinical studies. Treatment-emergent adverse events occurred in 46% with placebo, and at rates of 57.7%-80.8% in enpatoran treatment groups.
IN PRACTICE:
'The new findings from WILLOW provide promising evidence that enpatoran could enhance treatment options for these patients, addressing the suboptimal care typically available for those with CLE- and SLE-related skin manifestations,' said a spokesperson for EMD Serono, the healthcare business of Merck KGaA in the United States.
SOURCE:
Eric Morand, MD, of Monash University, Melbourne, Australia, presented the study at the 16th International Congress on Systemic Lupus Erythematosus in Toronto, Ontario, Canada.
LIMITATIONS:
The relatively small sample size of the trial and short duration could limit the ability to detect clinically meaningful differences in efficacy and longer-term outcomes.
DISCLOSURES:
Merck KGaA, based in Darmstadt, Germany, funded the research. Presenter and principal investigator Eric Morand, MD, of Monash University in Melbourne, Australia, reported financial relationships with 17 pharmaceutical companies, several of which manufacture lupus drugs.