Merck has received FDA Breakthrough Therapy designation for enpatoran, an investigational oral treatment for lupus patients with active skin manifestations, following positive Phase 2 clinical trial results.

The designation is intended to accelerate the development and regulatory review of medicines that could offer a substantial improvement over existing treatments for serious conditions. Enpatoran is being developed for patients with cutaneous manifestations of lupus, an area where there are currently no approved targeted therapies.

The FDA’s decision was supported by findings from the Phase 2 Willow trial, which demonstrated clinically meaningful improvements in lupus symptoms, particularly among patients with active skin disease.

Enpatoran is a selective toll-like receptor 7 and 8 (TLR7/8) inhibitor designed to reduce inflammation by targeting immune pathways involved in lupus.

David Weinreich, global head of research and development and chief medical officer for the healthcare business of Merck, said: “For the 85% of lupus patients whose disease includes skin manifestations, often associated with substantial physical and psychosocial burden, the lack of targeted treatment makes the disease hard to control.

“This Breakthrough Therapy designation demonstrates that enpatoran has the potential to redefine how we approach lupus, by addressing the visible burden of rash, while potentially driving benefit beyond the skin. We look forward to working with the FDA to potentially bring this much-needed option to patients as quickly as possible.”

The Willow study was a multicentre, randomised, double-blind, placebo-controlled Phase 2 dose-finding trial evaluating the safety and efficacy of orally administered enpatoran. It used an adaptive basket study design and enrolled patients with both cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE).

According to Merck, patients receiving enpatoran experienced clinically meaningful improvements in disease symptoms, with the greatest benefit observed among those with active cutaneous manifestations.

The company has already advanced the programme into late-stage clinical development, recently initiating the global Phase 3 Elowen 1 and Elowen 2 studies.

The trials will evaluate enpatoran alongside standard of care in approximately 400 patients across 266 sites in 26 countries. Researchers will assess the treatment’s effects on both skin and systemic disease activity, with changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) serving as the primary endpoint.

Lupus is a chronic autoimmune disease that can affect multiple organs, including the skin, joints, kidneys and central nervous system. Skin involvement occurs in around 72% to 85% of patients and is often one of the earliest signs of disease. These manifestations can cause permanent scarring, pain, photosensitivity and significant psychological burden, yet treatment options remain limited.

The FDA’s Breakthrough Therapy designation is reserved for investigational medicines that show preliminary clinical evidence of substantial improvement over available therapies. The designation provides increased interaction with the agency and may shorten development and review timelines.

Enpatoran remains an investigational medicine and has not been approved for use anywhere in the world.