At SLEuro 2026, Merck KGaA (Merck; known as EMD Serono in the US and Canada) presented new safety and tolerability data for enpatoran in development for cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Enpatoran is an orally administered toll-like receptor 7/8 inhibitor, which targets type 1 interferon and inflammatory cytokines, to alleviate inflammatory symptoms and achieve skin remissions in CLE and SLE patients. The safety data presented were derived from secondary endpoints of the Phase II (NCT05162586; Willow) trial, supporting enpatoran’s move into Phase III clinical trials for both SLE and CLE. The move is significant, given the lack of approved treatment options and sparse late-stage pipeline for CLE.
The Phase II proof-of-concept and dose-finding study evaluated the efficacy and safety of different doses of enpatoran (25mg, 50mg, and 100mg) against placebo, and involved 456 patients. The safety and tolerability endpoints measured the treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs) between enpatoran and placebo across the three different dosages at week 26. Results showed that TEAEs were present across all patient groups. The most common TEAEs were reported to be gastrointestinal complications and infections, which are not considered to be major adverse events, and which appeared to be consistent with the safety results from Phase Ib (NCT04647708), with no new complications identified. Additionally, Merck had already published the drug’s efficacy results in May 2025 from the Phase II trial (NCT05162586; Willow), which indicated that over 60% of patients had achieved Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in over 70% of the disease versus only about 11%–12% on placebo at week 16, showing a large separation from placebo suggesting promising efficacy.
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With enpatoran soon entering Phase III clinical trials (NCT07332481; ELOWEN-1 and NCT07355218; ELOWEN-2), the Phase II safety and efficacy results support the drug’s development, making the drug a promising immunosuppressor for the treatment of both SLE and CLE.
Today, the treatment landscape for CLE consists of off-label use of topical corticosteroids, antimalarials, and wide-spectrum immunosuppressants, with treatments approved for CLE. These treatments are widely known to have low efficacy and are commonly associated with undesirable safety profiles, including risk of severe infections and other complications such as cardiac disease and cancer, leading to poor prognosis. Due to the favourable safety outcomes presented at SLEuro 2026, combined with the promising efficacy data reported previously, enpatoran is well-positioned to address the need for effective and safe CLE treatment options.
Currently, there are only two drugs in late-stage development for CLE: AstraZeneca’s Saphnelo (anifrolumab) and Biogen’s litifilimab (NCT06015737; LAVENDER and NCT06044337; AMETHYST LTE, respectively). With Saphnelo already approved for SLE, its safety data is well established among clinicians; additionally, the recent approval of its subcutaneous formulation in
December 2025 provides a more convenient once-weekly self-injection option. Saphnelo and litifilimab have both already demonstrated efficacy against cutaneous manifestations of lupus comparable to enpatoran per respective Phase II outcomes. However, litifilimab’s Phase II clinical trial (NCT02847598; LILAC) also included a patient group with joint manifestations of CLE and SLE and reported a reduction of the average number of patients with joint manifestations, potentially offering an additional benefit for this sub-population. As such, despite positive outcomes for enpatoran, the oral formulation of the drug may be the primary differentiator from the other late-stage biologics in development, which are all injectables.
With a promising safety and efficacy profile supported by the Willow trial, enpatoran is well-positioned to kick off Phase III trials. Recruitment for ELOWEN-1 and ELOWEN-2 is expected to start at the end of March 2026 as the race to become the first approved agent in CLE continues.
