Researchers from EMD Serono and global collaborators shared promising results from Cohort B of the phase II trial of the WILLOW study, evaluating the safety and efficacy of enpatoran, a first-in-class oral toll-like receptor 7 and 8 (TLR7/8) inhibitor, in people with moderate to severe systemic lupus erythematosus (SLE). TLR7/8, can play a central role in lupus by signaling type I interferon (IFN) responses. Enpatoran aims to reduce the overactive immune response signaled by TLR7/8. Recent genetic studies have linked gain-of-function mutations in TLR7 to SLE, and preclinical research suggests TLR7/8 activation may also contribute to glucocorticoid resistance.
This phase II placebo-controlled study (WILLOW cohort B) evaluated enpatoran in 354 adults with moderate to severe SLE. Study participants were randomized to either receive placebo or enpatoran at different doses – 25 mg, 50 mg or 100 mg twice daily for a 24-week period using a one-sided Multiple Comparison Procedure-Modelling methodology. Although the study did not meet its primary endpoint of statistically significant dose-response relationship on the BILAD-based Composite Lupus Assessment (BICLA) at week 24, It was found that all groups treated with enpatoran showed greater response rates than placebo groups when examining disease activity and had reduced interferons in the blood that cause inflammation. More individuals on enpatoran were able to reduce their steroid dose while still seeing improvements in symptoms. Among those with severe skin involvement, up to 81.5% of those who received enpatoran had at least 50% improvement in rash severity, and 60.5% achieved 70% improvement, compared to 41.5% and 26.8% of placebo participants, respectively.
The side effects of enpatoran and placebo groups had similar outcomes; however, the treatment of enpatoran exhibited improved symptoms in those with lupus. These findings suggest that enpatoran is well-tolerated and may offer a targeted approach to reduce IFN-driven disease activity on lupus. However further research is needed. Learn more about medications used to treat lupus.
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