Over 90% of Lupus Patients Achieve Remission with Enpatoran: Merck KGaA Advances Potential First-in-Class Oral TLR7/8 Inhibitor into Phase 3 Trials

Merck KGaAToday announced its potential "first-in-class"Oral small molecule enpatoran in Phase 2 clinical trialPositive results in WILLOW. In receivingEnpatoran TreatmentIn patients with Cutaneous Lupus Erythematosus (CLE) and Systemic Lupus Erythematosus (SLE) with active lupus rash, over 90% of patientsA clinically meaningful reduction in disease activity.Based on these results,Merck KGaA is in discussions with regulatory authorities regarding the launch of a global Phase 3 clinical trial.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can affect multiple parts of the body, including the skin, joints, kidneys, and other organs. When the immune system mistakenly attacks healthy tissue, it can lead to inflammation, pain, and potential organ damage.Lupus has several types, with SLE and CLE being the two main forms. Symptoms range from mild to life-threatening and often include fatigue, joint pain, rashes, and organ involvement.Lupus affects women particularly severely. Although there are available treatments, many patients' needs remain unmet due to limited efficacy or side effects.

Enpatoran is aPotential "first-in-class"Selective Toll-like receptor (TLR) 7/8 inhibitor.By inhibiting the activation of TLR7/8, enpatoran may help reduce the production of pro-inflammatory cytokines and autoantibodies, potentially suppressing the underlying mechanisms of chronic inflammation and disease progression in lupus.

WILLOW is a global, multicenter, randomized, placebo-controlled Phase 2 clinical study evaluating the efficacy of three doses of enpatoran (25 mg, 50 mg, and 100 mg twice daily) versus placebo plus standard of care (SoC) over 24 weeks. The study features a unique design covering two lupus cohorts, including patients with active SLE and CLE. Cohort A focuses on patients with CLE or SLE with active lupus rash and evaluates organ-specific disease activity using the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score, a well-defined endpoint in CLE studies used to measure various aspects of mucocutaneous manifestations. Cohort B aims to assess the impact of enpatoran on systemic disease activity in SLE patients through the BICLA response endpoint.

The analysis shows,Cohort A met its primary endpoint, with patients showingA dose-response relationship was observed, with clinically meaningful improvement in CLASI-A scores at Week 16 (p=0.0002).In addition, at Week 24,Up to 91.3% of patients treated with enpatoran achieved a CLASI-50 response (≥50% improvement from baseline)., with up to 60.9% achieving CLASI-70 response (≥70% improvement from baseline), compared to 38.5% and 11.5% in the placebo group, respectively.

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In addition,Treatment with enpatoran in Cohort A also led to a rapid reduction in patients' interferon gene signature scores, starting from Week 2 and continuing through Week 24, confirming the role of the TLR7/8 pathway in CLE interferon activation.In this cohort, enpatoran was well-tolerated with manageable safety, consistent with previous studies, and no new safety signals were identified.

However, Cohort B of the WILLOW study did not meet the primary endpoint of dose response, but potential efficacy outcomes were observed in the pre-specified subgroups.Merck KGaA Expected to Announce at the European Alliance of Associations for Rheumatology Congress (EULAR 2025)The full results of the cohort.

References:
[1] Merck Presents Positive Phase 2 Data for Enpatoran Demonstrating Reduction in Disease Activity in Patients with Cutaneous Lupus Erythematosus (CLE) and Systemic Lupus Erythematosus (SLE) with Active Lupus Rash. Retrieved May 21, 2025 from https://www.businesswire.com/news/home/20250521318757/en/Merck-Presents-Positive-Phase-2-Data-for-Enpatoran-Demonstrating-Reduction-in-Disease-Activity-in-Patients-with-Cutaneous-Lupus-Erythematosus-CLE-and-Systemic-Lupus-Erythematosus-SLE-with-Active-Lupus-Rash

[2] R&D  UPDATE CALL 2021. Retrieved November 28, 2021, from  https://www.emdgroup.com/investors/events-and-presentations/conferences-and-roadshows/2021/us/211122_RD_UpdateCall_Final_NA.pdf

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