Merck Kgaa, Darmstadt, Germany Announces First Dose in Phase 3 Study with Enpatoran for Lupus Patients with Active Skin Manifestations

Merck KGaA, Darmstadt, Germany, a global science and technology company, announced the first patient was dosed in the Phase 3 program, ELOWEN-1 (NCT07332481) and ELOWEN-2 (NCT07355218), evaluating enpatoran in people living with lupus who experience active skin manifestations. Significant unmet need remains for 85% of lupus patients whose disease includes skin manifestations, often associated with substantial physical and psychosocial burden. Enpatoran, an oral TLR7/8 inhibitor, is designed for lupus patients with active cutaneous manifestations, with the goal of broadening the treatment paradigm beyond the current standards.

ELOWEN is a global Phase 3 program evaluating enpatoran?s impact on both skin and systemic symptoms in patients with lupus and potential links between skin and systemic disease activity. Enpatoran is an oral selective toll-like receptor (TLR) 7/8 inhibitor designed to modulate pathways central to lupus-related inflammation. By targeting these upstream drivers, enpatoran has the potential to impact disease activity and address a key aspect of the lupus mechanism that remains difficult to manage with current treatment approaches, while preserving the body?s broader immune function.

The ELOWEN program builds on Phase 2 findings, where enpatoran demonstrated clinically meaningful improvements in patients with active cutaneous manifestations, regardless of their underlying lupus diagnosis. These studies are designed to further explore how targeting shared inflammatory pathways may benefit patients across the lupus spectrum. Lupus is a chronic autoimmune disease that can affect multiple organ systems, including the skin, joints, kidneys and central nervous system.

Up to 85% of patients experience skin manifestations, which are among the most visible signs of disease and may reflect underlying immune-driven inflammation. Skin manifestations can be life-altering and sometimes are irreversible on their own. They can present as inflamed, photosensitive lesions on the face, scalp and other areas, and may lead to scarring or pigment changes.

Despite their prevalence and the fact that skin manifestations are the first sign of disease in nearly one third (29%) of cases, many patients still do not achieve adequate disease control. ELOWEN-1 and ELOWEN-2 are two global randomized, double-blind, placebo-controlled Phase 3 studies evaluating enpatoran taken twice daily versus placebo, on top of standard of care, in patients with lupus who have active cutaneous manifestations. The ELOWEN studies will be conducted in 266 sites in 26 countries.

Each study will recruit approximately 200 lupus participants, and the primary endpoint will be a change in CLASI-A from baseline. Enpatoran is an investigational, oral, selective inhibitor of toll-like receptors 7 and 8 (TLR7/8), which play a key role in immune pathways involved in lupus. Enpatoran has the potential to be the first targeted therapy for lupus patients with active cutaneous manifestations, with the goal of broadening the treatment paradigm beyond the current standards of care for patients with CLE and SLE.

Enpatoran is currently under clinical investigation and has not been approved for any use anywhere in the world. ELOWEN-1 (NCT07332481) and ELOWEN-2 (NCT07355218) are two global randomized, double-blind, placebo-controlled Phase 3 studies evaluating enpatoran taken twice daily versus placebo, on top of standard of care, in patients with lupus who have active cutaneous manifestations. The ELOWEN studies will be conducted in 266 sites in 26 countries.

Each study will recruit approximately 200 lupus participants, and the primary endpoint will be a change in CLASI-A from baseline. Lupus erythematosus is a chronic autoimmune disease characterized by inflammation that can affect multiple organs and systems in the body. The disease is heterogeneous, with symptoms ranging from mild to life-threatening, and often follows a relapsing-remitting course.

Cutaneous manifestations are common (72-85%) of patients and can occur alongside or independently of systemic involvement. Beyond their physical presentation, they are associated with increased disease burden, including scarring, psychological impact and reduced quality of life. Lupus disproportionately affects women and people of color, and many patients continue to experience unmet medical needs due to insufficient disease control or treatment-related side effects.