DARMSTADT, Germany — Merck KGaA, Darmstadt, Germany, said the first patient has been dosed in its Phase 3 ELOWEN program evaluating enpatoran in people with lupus who have active skin manifestations.
The global program includes two Phase 3 studies, ELOWEN-1 and ELOWEN-2, which are designed to evaluate the oral drug in patients with lupus who experience active cutaneous manifestations. The company said the studies will assess enpatoran’s effect on both skin and systemic symptoms, as well as potential links between skin and systemic disease activity.
“People living with lupus continue to face significant challenges in achieving disease control and are very often affected by itchy, painful and stigmatized skin manifestations,” said David Weinreich, Global Head of R&D, Merck KGaA, Darmstadt, Germany. “With enpatoran, we aim to target the underlying drivers of lupus and redefine how to approach the disease by understanding both visible skin manifestations and systemic activity.”
Enpatoran is an investigational oral selective toll-like receptor 7 and 8 inhibitor designed to modulate immune pathways involved in lupus-related inflammation. Merck KGaA said the drug is intended to target upstream drivers of disease activity while preserving 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,” said Professor Eric Morand, principal investigator. “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 several organ systems, including the skin, joints, kidneys and central nervous system. Merck KGaA said up to 85% of patients experience skin manifestations, which can include inflamed, photosensitive lesions on the face, scalp and other areas. These symptoms may lead to scarring or pigment changes and can carry a significant physical and psychosocial burden.
Skin manifestations are the first sign of disease in nearly 29% of lupus cases, according to the company, yet many patients still do not achieve adequate disease control.
“Skin symptoms impose a profound and multilayered burden that lingers long after flares subside. The lesions are visible, disfiguring and often painful, and the psychological weight can be equally debilitating, breeding a loss of identity that standard clinical assessments often fail to capture”, said Dr. Joy Buie, PhD, VP of Research at the Lupus Foundation of America. “These consequences erode participation in work, social life, and intimate relationships as self-consciousness and deliberate avoidance quietly reshape how patients navigate the world around them. It is vital we recognize skin manifestations as a visible and clinically actionable signal of underlying systemic disease “
ELOWEN-1 and ELOWEN-2 are randomized, double-blind, placebo-controlled Phase 3 studies evaluating twice-daily enpatoran against placebo on top of standard care. The studies will be conducted at 266 sites in 26 countries, with each study expected to enroll about 200 participants. The primary endpoint will be change from baseline in CLASI-A, a measure of cutaneous lupus disease activity.
Merck KGaA said enpatoran has the potential to become the first targeted therapy for lupus patients with active cutaneous manifestations, including patients with cutaneous lupus erythematosus and systemic lupus erythematosus. The drug remains investigational and has not been approved for any use anywhere in the world.
