Enpatoran Meaningfully Improves Active Lupus Rash

Enpatoran has demonstrated clinically meaningful improvements in disease activity in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) with active lupus rash.1

“Lupus can make navigating everyday life difficult. The skin manifestation, known as lupus rash, often comes with persistent itching, which can lead to scarring and hair loss. This can significantly impact the physical, emotional and social well-being of those living with lupus, underscoring the urgent need for effective treatments," Jan Klatt, Head of Development Unit Neurology & Immunology for the Healthcare business of Merck KGaA, Darmstadt, Germany, said in a statement.1 “We are encouraged by the WILLOW results, where we observed clinically meaningful efficacy with a favorable safety profile in people living with lupus rash. Based on these results, discussions with health authorities on a global Phase 3 program with enpatoran are underway.”

Enpatoran is an investigational, oral, novel toll-like receptors (TLR) 7/8 inhibitor. TLR7/8 are implicated in lupus pathogenesis and are associated with severe manifestations of the disease. Enpatoran is designed to enhance therapeutic efficacy while preserving the body's immune response, potentially overcoming limitations of existing lupus therapies.

The new data on enpatoran are from the Phase 2 WILLOW study (NCT05162586), full results from which will be presented at the 16th International Congress on Systemic Lupus Erythematosus (LUPUS 2025), taking place May 21-24 in Toronto.

WILLOW is a global, multicenter, randomized, placebo-controlled Phase 2 study evaluating 3 doses of enpatoran taken twice daily (25 mg, 50 mg and 100 mg) compared to placebo with standard of care (SoC) over 24 weeks. Cohort A focused on patients with CLE or SLE with active lupus rash and evaluated organ-specific disease activity using the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score and Cohort B was designed to evaluate the effect of enpatoran on systemic disease activity of SLE patients with the BICLA response endpoint.1

Cohort A met its primary endpoint, demonstrating a dose-response relationship and showing a clinically meaningful improvement in CLASI-A scores at Week 16 (P = .0002). Furthermore, up to 91.3% of patients receiving enpatoran achieved a CLASI-50 response (≥50% improvement from baseline), and up to 60.9% achieved a CLASI-70 response (≥70% improvement) at week 24, compared with 38.5% and 11.5%, respectively, in the placebo group. Enpatoran was well-tolerated in cohort A, with a manageable safety profile and no new safety signals identified.1

Investigators also observed a rapid reduction in interferon gene signature scores in cohort A beginning at Week 2, which was maintained to Week 24, confirming the involvement of the TLR7/8 pathway in interferon activation in CLE. However, Cohort B of the WILLOW study, did not meet its primary endpoint of dose response, although promising efficacy results were observed in prespecified subpopulations.2

“These new findings offer promising evidence that, with enpatoran, we may be able to advance outcomes, which remain suboptimal for most patients. The data from the WILLOW study further our understanding of TLR7/8 inhibition in SLE and CLE, which is a novel mechanism of action that may offer new hope for patients,” Principal investigator Prof. Eric Morand of Monash University and Monash Health, added.1

REFERENCES

1. EMD Serono Presents Positive Phase 2 Data for Enpatoran Demonstrating Reduction in Disease Activity in Patients with CLE and SLE with Active Lupus Rash. News release. EMD Serono. May 21, 2025. https://www.emdserono.com/us-en/company/news/press-releases/enpatoran-phase-2-data-21-05-2025.html

2. Beaney A. Merck KGaA’s lupus drug fails in SLE cohort of Phase II trial. News Article. Yahoo Finance. March 7, 2025. https://finance.yahoo.com/news/merck-lupus-drug-fails-sle-123936248.html?guccounter=2