Novel small-molecule TLR7/8 inhibitor shows therapeutic potential in lupus

The oral small-molecule TLR7/8 inhibitor enpatoran has shown a dose-dependent effect on disease activity in patients with active skin manifestations of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) in the phase II WILLOW trial.

The analysis involved cohort A of WILLOW, comprising 100 adult patients (median age 47 years, 77 percent female, 48 percent White) who had CLE only or SLE with mild or no extra-mucocutaneous disease activity (British Isles Lupus Assessment Group [BILAG]-2004 scores 1B, C, or D), in addition to a Cutaneous Lupus Disease Area and Severity Index–activity (CLASI-A) score of ≥8.

Patients were randomly assigned to receive enpatoran at a dose of 25 mg (n=23), 50 mg (n=25), or 100 mg (n=26) or placebo (n=26). Treatment was administered orally, twice a day for 24 weeks, in combination with standard of care.

Researchers assessed the dose–response effect of enpatoran on disease activity based on the percentage change from baseline in CLASI-A total score at week 16.

At week 16, enpatoran-treated patients had significantly reduced CLASI-A total score compared with those who received placebo, with the change in score commensurate with the dose: –64 percentage points with 25 mg, –68 percentage points with 50 mg, and –72 percentage points with 100 mg vs –44 percentage points with placebo (p=0.0002).

In terms of safety, upper respiratory tract infection was the most common treatment-emergent adverse event (AE), occurring in 8 percent of patients in the enpatoran 25-mg group, 15 percent in the 50-mg group, 19 percent in the 100-mg group, and 8 percent in the placebo group.

Serious AEs were documented in 4 percent of patients in the placebo group, 4 percent in the enpatoran 100-mg group, and 8 percent in the 25-mg group.