Litifilimab in cutaneous lupus: 27.2% clear skin at week 52 in Phase 2/3 AMETHYST trial

Data presented on Monday at the ACR Convergence 2026 annual meeting in Orlando show that litifilimab, an experimental antibody for cutaneous lupus erythematosus (CLE), maintained and deepened skin clearance over 52 weeks of treatment, according to techtimes.com techtimes.comtechtimes.comtechtimes.comOpen source ↗. Dr. Joseph Merola of UT Southwestern Medical Center reported outcomes from the AMETHYST Phase 2/3 trial, described as the first CLE study powered and designed to produce a full-year efficacy and safety dataset for a targeted drug. Hydroxychloroquine, a repurposed antimalarial, received its CLE approval in 1955.

AMETHYST results at 52 weeks

Among 59 participants who received litifilimab from the start, 27.2% reached clear or almost-clear skin (CLA-IGA-R score of 0 or 1) by week 52, up from 19.0% at week 24. Complete skin clearance was reached by 20.8%. Across the full cohort, 28.8% achieved CLASI-70 at week 52, up from 22% at week 24.

The 34 patients who were on placebo through week 24 were switched to litifilimab at that point. By week 52, 33.7% of them had clear or almost-clear skin, 48.5% had reached CLASI-50, and 27.5% had complete clearance, a category that stood at zero percent during the placebo period. In this group, 72.7% reported being much better or moderately better on a global assessment, and 75% reported improvement on a skin-specific assessment.

Serious adverse events were reported in 3.4% of participants (3 of 88 patients who received at least one dose in the open-label extension) techtimes.comtechtimes.comtechtimes.comOpen source ↗. Infections, including herpes-related events, were noted in a subset of patients, and no new safety signals appeared relative to the first 24 weeks.

Mechanism and next steps

Litifilimab targets BDCA2, a protein found on plasmacytoid dendritic cells. Binding of the antibody triggers internalization of the receptor, which suppresses the production of type I interferons and other proinflammatory cytokines; responses were measurable as early as week 4. Anifrolumab (Saphnelo), approved by the FDA for systemic lupus in 2021, instead blocks IFNAR, the receptor for type I interferons, and was not independently studied in CLE. The earlier LILAC Phase 2 trial was published in the New England Journal of Medicine in 2022.

The FDA granted litifilimab a designation for CLE in January 2026 that places the program on an expedited development pathway. Part B of AMETHYST, a pivotal Phase 3 blinded extension, is ongoing, with topline results expected in the first half of 2027. Biogen is also running the TOPAZ-1 and TOPAZ-2 Phase 3 trials in systemic lupus erythematosus, with primary completion estimated in late 2026.