Merck KGaA, Darmstadt, Germany, has moved its investigational lupus therapy enpatoran into late-stage testing, announcing that the first patient has been dosed in its global Phase 3 program. 

The trials -- ELOWEN-1 and ELOWEN-2 -- are designed to evaluate the drug in people living with lupus who experience active skin manifestations. 

The company is positioning enpatoran as a targeted approach to one of lupus’ most visible and persistent challenges: inflammatory skin disease driven by immune dysfunction. 

“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 oral, selective toll-like receptor (TLR) 7/8 inhibitor designed to dampen key inflammatory pathways believed to drive lupus. By acting upstream in the immune cascade, the therapy is intended to reduce 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 multiple organs, including skin, joints, kidneys and the central nervous system. Skin involvement is especially common, affecting up to 85% of patients, and often represents one of the earliest and most visible signs of disease. 

“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 Joy Buie, 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." 

The Phase 3 ELOWEN studies are randomized, double-blind, placebo-controlled trials evaluating twice-daily enpatoran on top of standard care. Conducted across 266 sites in 26 countries, each study will enroll around 200 participants. The primary endpoint is change in CLASI-A score from baseline, a key measure of cutaneous lupus severity.