Merck KGaA Details Lupus Trial Setback, Eyes Regulatory Approval

Highlights

• Merck’s phase 2 WILLOW study of enpatoran showed success in cohort A but failure to meet the primary endpoint in cohort B.
• Cohort B missed its 24-week primary composite endpoint but showed promising secondary endpoint results, particularly in patients with active skin disease.
• Subgroup analysis revealed up to 58.6% BICLA response rate and significant skin disease improvement among enpatoran recipients.
• Higher response rates observed in patients with elevated corticosteroid use, though detailed data remains undisclosed.
• Merck plans to engage regulators soon to explore approval pathways for enpatoran.
• Enpatoran is one of two advanced assets in Merck’s neurology and immunology portfolio; the other is cladribine in phase 3 for myasthenia gravis.

Trial Overview and Mixed Results

Merck KGaA has provided additional insights into the outcomes of its phase 2 WILLOW study evaluating enpatoran, an oral TLR7/8 inhibitor aimed at treating lupus. The trial tested the drug in two distinct cohorts. Cohort A, which included patients with cutaneous lupus erythematosus or systemic lupus erythematosus (SLE), successfully met its primary endpoint by demonstrating a clinically meaningful improvement at week 16 as measured by the CLE Disease Area and Severity Index.

However, cohort B, which enrolled patients solely with SLE, failed to meet its primary endpoint. This endpoint measured responses on a composite scale after 24 weeks of daily dosing. Merck had previously disclosed this setback in March but has since emphasized secondary findings to support the drug’s continued development.

Secondary Endpoint Findings and Subgroup Benefits

At the 2025 European Congress of Rheumatology in Barcelona, Merck presented data indicating that all doses of enpatoran in cohort B were linked to higher response rates compared to placebo, based on the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate. Despite this, the company did not release detailed data and confirmed that the primary endpoint was missed.

Significantly, in a subgroup of patients with active skin disease, BICLA response rates reached up to 58.6% for those treated with enpatoran, versus 31.7% for placebo. Furthermore, more than 58% of enpatoran recipients showed at least a 70% improvement in skin disease activity, compared to 26.8% in the placebo group. Additionally, patients with high corticosteroid use exhibited “higher and relevant” BICLA response rates, though Merck withheld specific numbers.

Company Perspective and Next Steps

Jan Klatt, Head of Development Unit Neurology and Immunology at Merck’s Healthcare business, stated, “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.”

Klatt further noted, “We are set to initiate regulatory discussions with key health authorities to determine the most effective pathway for bringing enpatoran to patients.”

Pipeline Context

Enpatoran, which is also being studied for idiopathic inflammatory myopathies, stands as one of Merck’s two most advanced neurology and immunology pipeline assets. The company’s other late-stage candidate, cladribine, is currently in phase 3 development targeting generalized myasthenia gravis.