DARMSTADT, GERMANY -- Merck, a leading science and technology company, announced the presentation of detailed results from Cohort B of the global Phase 2 WILLOW study (NCT05162586) evaluating enpatoran, an investigational, oral, novel TLR7/8 inhibitor in systemic lupus erythematosus (SLE). Although it did not meet the primary endpoint of dose-response relationship, when compared to placebo, enpatoran demonstrated improvements in measures of both systemic and cutaneous disease activity in prespecified SLE subpopulations despite standard of care (SoC), including those with active cutaneous manifestations at baseline [(CLASI-A) ≥8], and was overall well tolerated. These findings will be presented in a late-breaking oral presentation at the 2025 European Congress of Rheumatology (EULAR) in Barcelona (Abstract # LB0004).

“Analyses of Cohort B contribute to our understanding of enpatoran’s potential to address the critical unmet needs for patients living with lupus, including those experiencing significant skin manifestations. These manifestations are often part of the systemic activity or flare, which can be painful and have a considerable impact on quality of life,” said principal investigator Prof. Eric Morand, from Monash University and Monash Health. “The improvements observed in key disease measures represent a meaningful advancement in our ongoing investigation of the TLR7/8 inhibition approach for patients insufficiently managed by current therapies.”

WILLOW is a global, multicenter, randomized, placebo-controlled Phase 2 study evaluating three doses of oral enpatoran taken twice daily (25 mg, 50 mg and 100 mg) versus placebo plus SoC over 24 weeks. The study features a unique design across two lupus cohorts, including both patients with active SLE and cutaneous lupus erythematosus (CLE). Cohort B of the study was designed to evaluate the dose-response relationship of enpatoran in reducing disease activity, based on the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response rate at Week 24 and enrolled SLE patients who had moderate or severe active disease despite SoC.

Cohort B showed positive results in secondary and exploratory endpoints and within prespecified patient subpopulations. In patients with active skin disease (CLASI-A ≥8), BICLA response rates were up to 58.6% while placebo response rates were 31.7%, and up to 60.5% of patients receiving enpatoran showed a CLASI-70 response, compared with 26.8% for placebo, at Week 24. In addition, the subgroups of patients with high corticosteroid (prednisone-equivalent ≥10 mg/day) use and those with high interferon gene signature (IFN-GS) at baseline also showed higher and relevant BICLA response rates for enpatoran compared to placebo.

As presented earlier this year at LUPUS 2025, Cohort A analyses from the WILLOW study showed clinically meaningful improvement in disease activity in patients with CLE and mild SLE with active lupus rash at Weeks 16 and 24. Overall, for skin-related signs and symptoms, comparable improvements were observed in Cohort B relative to Cohort A, reinforcing the potential efficacy of enpatoran in patients with cutaneous manifestations of lupus erythematosus with or without systemic disease.

“The efficacy and tolerability results from Cohort B, including among those with active skin involvement—a manifestation that affects most lupus patients—are consistent with our observations from Cohort A. The lupus rash is not only a visible symptom but is also closely linked to the underlying systemic activity of lupus,” said Jan Klatt, Head of Development Unit Neurology & Immunology for the Healthcare business of Merck. “We are set to initiate regulatory discussions with key health authorities to determine the most effective pathway for bringing enpatoran to patients.”

Enpatoran was well-tolerated and exhibited a manageable safety profile consistent with previous studies, with no new safety signals identified. Rates of treatment-emergent adverse events (TEAEs) were comparable between all enpatoran arms and placebo, ranging from 60.6% to 64.2%, and the most frequently reported TEAEs were infections and infestations. These results further support the anticipated favorable safety profile of enpatoran.